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Conserved domains on  [gi|966980062|ref|XP_014967305|]
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intersectin-2 isoform X1 [Macaca mulatta]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_13 pfam16652
Pleckstrin homology domain;
1412-1555 2.47e-85

Pleckstrin homology domain;


:

Pssm-ID: 465218  Cd Length: 143  Bit Score: 275.04  E-value: 2.47e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1412 VQCEGLAEQLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKT 1491
Cdd:pfam16652    1 VQCEGLSEQLVFNSLTNCLGPRKLLHSGKLYKVKSNKELVGFLFNDFLLLTQPVKPLS-SAGTDKLFSSKSNIQYKMYKT 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062  1492 PIFLNEVLVKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKKKRE 1555
Cdd:pfam16652   80 PIFLNEVMVKLPTDPSSSEPTFQLSHIDRVYTLKAESPNERTAWVKKIKEASELYIETEKKKRE 143
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
1555-1689 5.02e-82

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


:

Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 265.02  E-value: 5.02e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1555 EKAYQARSQKTSGIGRLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCL 1634
Cdd:cd08375     1 EKAYLARSQRASGIGRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCI 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1635 TLFDRDQFSPDDFLGRTEIPVAKIRTE-QESKGPVTRRLLLHEVPTGEVWVRFDLQ 1689
Cdd:cd08375    81 TVFDRDFFSPDDFLGRTEIRVADILKEtKESKGPITKRLLLHEVPTGEVVVKLDLQ 136
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
1214-1394 6.53e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


:

Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 160.93  E-value: 6.53e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1214 IHELIQTEERYMADLQLVVEVFQKRM-AESGFLTEGEMALIFVNWKELIMSNTKLLKALRVRKKTggEKMPVQMVGDILA 1292
Cdd:smart00325    2 LKELLQTERNYVRDLKLLVEVFLKPLkKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEE--WDDSVERIGDVFL 79
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1293 AELSHMQAYIRFCSCQLNGAALLQQKtDEDTDFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTPESH 1372
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158
                           170       180
                    ....*....|....*....|..
gi 966980062   1373 ADHSSLKLALERAEELCSQVNE 1394
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
759-815 3.03e-37

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212921 [Multi-domain]  Cd Length: 57  Bit Score: 134.23  E-value: 3.03e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  759 LVNYRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11988     1 LVNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1130-1183 2.14e-35

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 128.95  E-value: 2.14e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11996     1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54
SH3_Intersectin2_4 cd11994
Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1057-1115 1.27e-34

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212927  Cd Length: 59  Bit Score: 126.58  E-value: 1.27e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARGKKRQKGWFPASHVKLL 1115
Cdd:cd11994     1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQARGKKRQKGWFPASHVKLL 59
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
15-107 3.31e-34

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


:

Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 127.01  E-value: 3.31e-34
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062     15 MWAITSEERTKHDRQFDNLKPSG-GYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQGQ 93
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQdGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80
                            90
                    ....*....|....
gi 966980062     94 QLPVVLPPIMKQPP 107
Cdd:smart00027   81 PIPASLPPSLIPPS 94
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
902-953 4.91e-34

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 124.77  E-value: 4.91e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11990     1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
985-1036 6.27e-34

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212925  Cd Length: 52  Bit Score: 124.35  E-value: 6.27e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11992     1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVRP 52
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
237-316 3.52e-29

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


:

Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 112.37  E-value: 3.52e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062    237 EWAVPQPSRLKYRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLTDMAKAGQ 316
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80
PTZ00121 super family cl31754
MAEBL; Provisional
346-756 3.07e-14

MAEBL; Provisional


The actual alignment was detected with superfamily member PTZ00121:

Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 78.64  E-value: 3.07e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  346 SYQKIQEEEPQKKLpvtfEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKR 425
Cdd:PTZ00121 1298 AEEKKKADEAKKKA----EEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKK 1373
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  426 LEKQRELErqreeerrkeierreAAKQELERQRRLE------------WERIRRQELLNQKNRE----QEEIVRLNSKKK 489
Cdd:PTZ00121 1374 EEAKKKAD---------------AAKKKAEEKKKADeakkkaeedkkkADELKKAAAAKKKADEakkkAEEKKKADEAKK 1438
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  490 SLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCD--LEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKN 567
Cdd:PTZ00121 1439 KAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEeaKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKA 1518
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  568 MQFSNTPDSGVSLLHKKS--LEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFL 645
Cdd:PTZ00121 1519 EEAKKADEAKKAEEAKKAdeAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVM 1598
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  646 LLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKE-----NLWKENLRREEEEKQKRLQ 720
Cdd:PTZ00121 1599 KLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKaeeenKIKAAEEAKKAEEDKKKAE 1678
                         410       420       430
                  ....*....|....*....|....*....|....*..
gi 966980062  721 EEKTQEkiqEEERKAEEK-QRKDKDTLKVEEKQRETA 756
Cdd:PTZ00121 1679 EAKKAE---EDEKKAAEAlKKEAEEAKKAEELKKKEA 1712
KLF3_N super family cl40586
N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called ...
91-184 1.06e-03

N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called Krueppel-like factor 3 and originally called Basic Kruppel-like Factor/BKLF), was the third member of the KLF family of zinc finger transcription factors to be discovered. KLF3 possesses a wide range of biological impacts on regulating apoptosis, differentiation, and proliferation in various tissues during the entire progression process. It has been proposed as a tumor suppressor in colorectal cancer. It appears to function predominantly as a repressor of transcription, turning genes off by recruiting the C-terminal Binding Protein co-repressors CtBP1 and CtBP2. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, through the Proline-X-Aspartate-Leucine-Serine (PXDLS) motif. CtBP in turn recruits histone modifying enzymes to alter chromatin and repress gene expression. KLF3 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF3.


The actual alignment was detected with superfamily member cd21577:

Pssm-ID: 410554 [Multi-domain]  Cd Length: 214  Bit Score: 42.33  E-value: 1.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   91 QGQQLPVVL-------PPimkqPPMFSPLISARFGMGSMPNLSIPQP---LPPAAPITSLSSATSGTnLPPLMMPAPLVP 160
Cdd:cd21577    16 HSQLEPVDLslskrssPP----SSSSSSSSSSSSSSSPSSRASPPSPyskSSPPSPPQQRPLSPPLS-LPPPVAPPPLSP 90
                          90       100
                  ....*....|....*....|....
gi 966980062  161 SVSTSSLPNGTASLIQPLSIPYSS 184
Cdd:cd21577    91 GSVPGGLPVISPVMVQPVPVLYPP 114
 
Name Accession Description Interval E-value
PH_13 pfam16652
Pleckstrin homology domain;
1412-1555 2.47e-85

Pleckstrin homology domain;


Pssm-ID: 465218  Cd Length: 143  Bit Score: 275.04  E-value: 2.47e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1412 VQCEGLAEQLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKT 1491
Cdd:pfam16652    1 VQCEGLSEQLVFNSLTNCLGPRKLLHSGKLYKVKSNKELVGFLFNDFLLLTQPVKPLS-SAGTDKLFSSKSNIQYKMYKT 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062  1492 PIFLNEVLVKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKKKRE 1555
Cdd:pfam16652   80 PIFLNEVMVKLPTDPSSSEPTFQLSHIDRVYTLKAESPNERTAWVKKIKEASELYIETEKKKRE 143
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
1555-1689 5.02e-82

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 265.02  E-value: 5.02e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1555 EKAYQARSQKTSGIGRLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCL 1634
Cdd:cd08375     1 EKAYLARSQRASGIGRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCI 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1635 TLFDRDQFSPDDFLGRTEIPVAKIRTE-QESKGPVTRRLLLHEVPTGEVWVRFDLQ 1689
Cdd:cd08375    81 TVFDRDFFSPDDFLGRTEIRVADILKEtKESKGPITKRLLLHEVPTGEVVVKLDLQ 136
PH_ITSN cd13264
Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in ...
1420-1552 1.69e-73

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270084  Cd Length: 132  Bit Score: 240.82  E-value: 1.69e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1420 QLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKTPIFLNEVL 1499
Cdd:cd13264     1 QLIFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQPIKPLG-SSGNDFVFDNKANIQYKMYKTPIFLNEVL 79
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1500 VKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKK 1552
Cdd:cd13264    80 VKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 132
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
1214-1394 6.53e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 160.93  E-value: 6.53e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1214 IHELIQTEERYMADLQLVVEVFQKRM-AESGFLTEGEMALIFVNWKELIMSNTKLLKALRVRKKTggEKMPVQMVGDILA 1292
Cdd:smart00325    2 LKELLQTERNYVRDLKLLVEVFLKPLkKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEE--WDDSVERIGDVFL 79
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1293 AELSHMQAYIRFCSCQLNGAALLQQKtDEDTDFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTPESH 1372
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158
                           170       180
                    ....*....|....*....|..
gi 966980062   1373 ADHSSLKLALERAEELCSQVNE 1394
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
1210-1393 7.89e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 160.54  E-value: 7.89e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1210 RQGYIHELIQTEERYMADLQLVVEVFQKRMAESG-FLTEGEMALIFVNWKELIMSNTKLLKALRVRKKTGGekMPVQMVG 1288
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELlPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1289 DILAAELSHMQAYIRFCSCQLNGAALLQQKTDEDTDFKEFLKKLasDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENT 1368
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156
                         170       180
                  ....*....|....*....|....*
gi 966980062 1369 PESHADHSSLKLALERAEELCSQVN 1393
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
1214-1393 5.18e-44

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 157.85  E-value: 5.18e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1214 IHELIQTEERYMADLQLVVEVFQKRMAESGFLTEGEMALIFVNWKELIMSNTKLLkaLRVRKKtggEKMPVQMVGDILAA 1293
Cdd:pfam00621    2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLK---EWISIQRIGDIFLK 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1294 ELSHMQAYIRFCSCQLNGAALLQQKTDEDTDFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTPESHA 1373
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156
                          170       180
                   ....*....|....*....|
gi 966980062  1374 DHSSLKLALERAEELCSQVN 1393
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
759-815 3.03e-37

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212921 [Multi-domain]  Cd Length: 57  Bit Score: 134.23  E-value: 3.03e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  759 LVNYRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11988     1 LVNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1130-1183 2.14e-35

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 128.95  E-value: 2.14e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11996     1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54
SH3_Intersectin2_4 cd11994
Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1057-1115 1.27e-34

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212927  Cd Length: 59  Bit Score: 126.58  E-value: 1.27e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARGKKRQKGWFPASHVKLL 1115
Cdd:cd11994     1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQARGKKRQKGWFPASHVKLL 59
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
15-107 3.31e-34

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 127.01  E-value: 3.31e-34
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062     15 MWAITSEERTKHDRQFDNLKPSG-GYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQGQ 93
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQdGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80
                            90
                    ....*....|....
gi 966980062     94 QLPVVLPPIMKQPP 107
Cdd:smart00027   81 PIPASLPPSLIPPS 94
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
902-953 4.91e-34

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 124.77  E-value: 4.91e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11990     1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
985-1036 6.27e-34

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212925  Cd Length: 52  Bit Score: 124.35  E-value: 6.27e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11992     1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVRP 52
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
237-316 3.52e-29

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 112.37  E-value: 3.52e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062    237 EWAVPQPSRLKYRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLTDMAKAGQ 316
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80
C2 pfam00168
C2 domain;
1569-1658 3.45e-26

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 104.32  E-value: 3.45e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1569 GRLMVHVIEATELKACKPNGKSNPYCEISM--GSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDD 1646
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80
                           90
                   ....*....|..
gi 966980062  1647 FLGRTEIPVAKI 1658
Cdd:pfam00168   81 FIGEVRIPLSEL 92
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1570-1666 4.79e-25

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 101.02  E-value: 4.79e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1570 RLMVHVIEATELKACKPNGKSNPYCEISMG---SQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDD 1646
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80
                            90       100
                    ....*....|....*....|
gi 966980062   1647 FLGRTEIPVAKIRTEQESKG 1666
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEK 100
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
248-314 2.96e-24

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 97.29  E-value: 2.96e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  248 YRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLTDMAKA 314
Cdd:cd00052     1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
27-91 9.80e-24

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 95.75  E-value: 9.80e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   27 DRQFDNLKPSG-GYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQ 91
Cdd:cd00052     2 DQIFRSLDPDGdGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
1128-1182 2.06e-20

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 86.05  E-value: 2.06e-20
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   1128 PVCQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN-GVTGLFPSNYVK 1182
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
762-814 2.12e-16

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 74.50  E-value: 2.12e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 966980062    762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 814
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKS--DDGWWKGRLGrGKEGLFPSNYVE 56
SH3_9 pfam14604
Variant SH3 domain;
1134-1182 2.93e-16

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 74.19  E-value: 2.93e-16
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 966980062  1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
982-1035 2.50e-15

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 71.80  E-value: 2.50e-15
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062    982 VGEEYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGD-RSGIFPSNYVK 1035
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKsDDGWWKGRLGRgKEGLFPSNYVE 56
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
902-952 1.18e-14

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 69.87  E-value: 1.18e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 966980062    902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGR-GWFPKSYVK 952
Cdd:smart00326    4 QVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKGRLGRGKeGLFPSNYVE 56
PTZ00121 PTZ00121
MAEBL; Provisional
346-756 3.07e-14

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 78.64  E-value: 3.07e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  346 SYQKIQEEEPQKKLpvtfEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKR 425
Cdd:PTZ00121 1298 AEEKKKADEAKKKA----EEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKK 1373
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  426 LEKQRELErqreeerrkeierreAAKQELERQRRLE------------WERIRRQELLNQKNRE----QEEIVRLNSKKK 489
Cdd:PTZ00121 1374 EEAKKKAD---------------AAKKKAEEKKKADeakkkaeedkkkADELKKAAAAKKKADEakkkAEEKKKADEAKK 1438
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  490 SLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCD--LEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKN 567
Cdd:PTZ00121 1439 KAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEeaKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKA 1518
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  568 MQFSNTPDSGVSLLHKKS--LEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFL 645
Cdd:PTZ00121 1519 EEAKKADEAKKAEEAKKAdeAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVM 1598
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  646 LLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKE-----NLWKENLRREEEEKQKRLQ 720
Cdd:PTZ00121 1599 KLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKaeeenKIKAAEEAKKAEEDKKKAE 1678
                         410       420       430
                  ....*....|....*....|....*....|....*..
gi 966980062  721 EEKTQEkiqEEERKAEEK-QRKDKDTLKVEEKQRETA 756
Cdd:PTZ00121 1679 EAKKAE---EDEKKAAEAlKKEAEEAKKAEELKKKEA 1712
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
902-954 3.45e-13

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 65.31  E-value: 3.45e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966980062   902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 954
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGRVGLVPSTAVEEI 54
DUF5401 pfam17380
Family of unknown function (DUF5401); This is a family of unknown function found in ...
335-754 4.40e-13

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.


Pssm-ID: 375164 [Multi-domain]  Cd Length: 722  Bit Score: 74.39  E-value: 4.40e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   335 KQIDSINGTLPSYQKIQ---EEEPQKKLPVTFEDKRKANYERGNM-ELEKRRQAL-VEQQQREAERKAQKEKEEWERKQR 409
Cdd:pfam17380  221 KEVQGMPHTLAPYEKMErrkESFNLAEDVTTMTPEYTVRYNGQTMtENEFLNQLLhIVQHQKAVSERQQQEKFEKMEQER 300
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   410 ELQEQEwKKQLELEKRleKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQKNR-EQEEIVRLNSKK 488
Cdd:pfam17380  301 LRQEKE-EKAREVERR--RKLEEAEKARQAEMDRQAAIYAEQERMAMERERELERIRQEERKRELERiRQEEIAMEISRM 377
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   489 KslhlELEALNGKHQQISGRLQ---DVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQnkliylvpEKQLLNERI 565
Cdd:pfam17380  378 R----ELERLQMERQQKNERVRqelEAARKVKILEEERQRKIQQQKVEMEQIRAEQEEARQRE--------VRRLEEERA 445
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   566 KNMQfsntpdsgvsLLHKKSLEKQELCQRLKEQldalEKETASKLSEMDsynnqlkcgnmddsvlqcllsllsclnnlfl 645
Cdd:pfam17380  446 REME----------RVRLEEQERQQQVERLRQQ----EEERKRKKLELE------------------------------- 480
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   646 llKELREtcntQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDeaaRKAKQGKENLWKENLRREEEEKQKRLQEEKTQ 725
Cdd:pfam17380  481 --KEKRD----RKRAEEQRRKILEKELEERKQAMIEEERKRKLLE---KEMEERQKAIYEEERRREAEEERRKQQEMEER 551
                          410       420
                   ....*....|....*....|....*....
gi 966980062   726 EKIQEEERKAEEKQRKdkdtLKVEEKQRE 754
Cdd:pfam17380  552 RRIQEQMRKATEERSR----LEAMERERE 576
SH3_9 pfam14604
Variant SH3 domain;
764-814 7.35e-13

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 64.56  E-value: 7.35e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 966980062   764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEES--EDGWWEGINTGRTGLVPANYVE 49
EF-hand_4 pfam12763
Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin ...
30-86 1.02e-12

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.


Pssm-ID: 289529  Cd Length: 104  Bit Score: 65.86  E-value: 1.02e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062    30 FDNLKPSGGYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLI 86
Cdd:pfam12763   16 FSGLKPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLI 72
EF-hand_4 pfam12763
Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin ...
247-311 1.86e-12

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.


Pssm-ID: 289529  Cd Length: 104  Bit Score: 65.09  E-value: 1.86e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   247 KYRQKFNSLdKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLT-DM 311
Cdd:pfam12763   11 KYWEIFSGL-KPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIfDL 75
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
987-1031 1.81e-11

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 60.29  E-value: 1.81e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966980062   987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTG-SIGDRSGIFPS 1031
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKsEDGWWKGrNKGGKEGLIPS 47
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
1054-1113 2.92e-11

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 60.24  E-value: 2.92e-11
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1054 KPEIAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELqargKKRQKGWFPASHVK 1113
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL----GRGKEGLFPSNYVE 56
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
452-739 5.04e-11

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 68.16  E-value: 5.04e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   452 QELERQ-RRLEWERIRRQELLNQKNREQE--------EIVRLNSKKKSLHLELEALNGKHQQISGRLQdvrlKKQTQKTE 522
Cdd:TIGR02168  196 NELERQlKSLERQAEKAERYKELKAELRElelallvlRLEELREELEELQEELKEAEEELEELTAELQ----ELEEKLEE 271
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   523 LEVLDKQCDLEIMEIKQLQQELQEYQNKliyLVPEKQLLNERIKNMQFSNTPDSGVSLLHKKSL-EKQELCQRLKEQLDA 601
Cdd:TIGR02168  272 LRLEVSELEEEIEELQKELYALANEISR---LEQQKQILRERLANLERQLEELEAQLEELESKLdELAEELAELEEKLEE 348
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   602 LEKETASKLSEMDSYNNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNTQQLALEQLYKIK--RDKLKEIERKR 679
Cdd:TIGR02168  349 LKEELESLEAELEELEAELE--ELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEdrRERLQQEIEEL 426
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062   680 LELIQKKKLEDEAARKA--KQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQ 739
Cdd:TIGR02168  427 LKKLEEAELKELQAELEelEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQ 488
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
377-771 9.36e-11

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 66.88  E-value: 9.36e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  377 ELEKRRQALveqqQREAErKAqkekeeweRKQRELQEQEwkKQLELEKRLekqrelerqreeerrkeierreaakqeler 456
Cdd:COG1196   197 ELERQLEPL----ERQAE-KA--------ERYRELKEEL--KELEAELLL------------------------------ 231
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  457 qRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIME 536
Cdd:COG1196   232 -LKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEER 310
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  537 IKQLQQelqeyqnkliylvpEKQLLNERIKnmqfsntpdsgvSLLHKKSLEKQELcQRLKEQLDALEKETASKLSEMDSY 616
Cdd:COG1196   311 RRELEE--------------RLEELEEELA------------ELEEELEELEEEL-EELEEELEEAEEELEEAEAELAEA 363
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  617 NNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELREtcntQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKA 696
Cdd:COG1196   364 EEALL--EAEAELAEAEEELEELAEELLEALRAAAE----LAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEE 437
                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  697 KQGKENLwkenLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASVLVNYRALYPFEAR 771
Cdd:COG1196   438 EEEEEAL----EEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLE 508
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
1207-1461 1.37e-10

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 66.45  E-value: 1.37e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1207 ERKRQGYIHELIQTEERYMADLQLVVEVFQKRMAESGFLTEGE----MALIFVNWKELIMSNTKLLKALRVRKKTggeKM 1282
Cdd:COG5422   482 EIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQCL---SP 558
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1283 PVQMVGDILAAELSHMQAYIRFCSCQLNGAALLQQKTDEDTDFKEF--LKKLASDPRCKGmpLSSFLLKPMQRITRYPLL 1360
Cdd:COG5422   559 IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFdhEVERLDESRKLE--LDGYLTKPTTRLARYPLL 636
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1361 IRSILENTPESHADHSSLKLALERAEELCSQVNEGVREKENsdRLEWIQahvqcegLAEQLIFNSLTNCLG----PRKLL 1436
Cdd:COG5422   637 LEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEN--RGDLFH-------LNQQLLFKPEYVNLGlndeYRKII 707
                         250       260       270
                  ....*....|....*....|....*....|..
gi 966980062 1437 HSGKLYKTKSNK-------ELHGFLFNDFLLL 1461
Cdd:COG5422   708 FKGVLKRKAKSKtdgslrgDIQFFLLDNMLLF 739
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1569-1669 2.90e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 59.00  E-value: 2.90e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGSQS-YTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDF 1647
Cdd:COG5038  1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSvYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDL 1119
                          90       100
                  ....*....|....*....|....
gi 966980062 1648 LGRTEIPVAKIRTEQE--SKGPVT 1669
Cdd:COG5038  1120 LGTAEIDLSKLEPGGTtnSNIPLD 1143
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
1063-1109 7.20e-08

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 50.28  E-value: 7.20e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966980062  1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELqargKKRQKGWFPA 1109
Cdd:pfam00018    5 DYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRN----KGGKEGLIPS 47
TOPEUc smart00435
DNA Topoisomerase I (eukaryota); DNA Topoisomerase I (eukaryota), DNA topoisomerase V, Vaccina ...
654-747 9.83e-05

DNA Topoisomerase I (eukaryota); DNA Topoisomerase I (eukaryota), DNA topoisomerase V, Vaccina virus topoisomerase, Variola virus topoisomerase, Shope fibroma virus topoisomeras


Pssm-ID: 214661 [Multi-domain]  Cd Length: 391  Bit Score: 46.57  E-value: 9.83e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062    654 CNTQQLA----LEQLYKIKrDKLKEIERKRLELiQKKKLEDEAARKAK---QGKENLWKENLRREEEEKQKRLQ-EEKTQ 725
Cdd:smart00435  265 CNHQRTVskthEKSMEKLQ-EKIKALKYQLKRL-KKMILLFEMISDLKrklKSKFERDNEKLDAEVKEKKKEKKkEEKKK 342
                            90       100
                    ....*....|....*....|....
gi 966980062    726 EKIQEEERKAE--EKQRKDKDTLK 747
Cdd:smart00435  343 KQIERLEERIEklEVQATDKEENK 366
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
249-307 3.09e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 42.47  E-value: 3.09e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062  249 RQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMH 307
Cdd:COG5126    72 RAAFDLLDTDGDGKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAVR 130
KLF3_N cd21577
N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called ...
91-184 1.06e-03

N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called Krueppel-like factor 3 and originally called Basic Kruppel-like Factor/BKLF), was the third member of the KLF family of zinc finger transcription factors to be discovered. KLF3 possesses a wide range of biological impacts on regulating apoptosis, differentiation, and proliferation in various tissues during the entire progression process. It has been proposed as a tumor suppressor in colorectal cancer. It appears to function predominantly as a repressor of transcription, turning genes off by recruiting the C-terminal Binding Protein co-repressors CtBP1 and CtBP2. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, through the Proline-X-Aspartate-Leucine-Serine (PXDLS) motif. CtBP in turn recruits histone modifying enzymes to alter chromatin and repress gene expression. KLF3 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF3.


Pssm-ID: 410554 [Multi-domain]  Cd Length: 214  Bit Score: 42.33  E-value: 1.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   91 QGQQLPVVL-------PPimkqPPMFSPLISARFGMGSMPNLSIPQP---LPPAAPITSLSSATSGTnLPPLMMPAPLVP 160
Cdd:cd21577    16 HSQLEPVDLslskrssPP----SSSSSSSSSSSSSSSPSSRASPPSPyskSSPPSPPQQRPLSPPLS-LPPPVAPPPLSP 90
                          90       100
                  ....*....|....*....|....
gi 966980062  161 SVSTSSLPNGTASLIQPLSIPYSS 184
Cdd:cd21577    91 GSVPGGLPVISPVMVQPVPVLYPP 114
UDM1_RNF168 cd22265
UDM1 (ubiquitin-dependent DSB recruitment module 1) domain found in RING finger protein 168; ...
691-746 1.90e-03

UDM1 (ubiquitin-dependent DSB recruitment module 1) domain found in RING finger protein 168; RING finger protein 168 (RNF168) is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. Together with RNF8, RNF168 functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates such as H2A and H2AX. With H2AK13/15 ubiquitylation, it facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. In addition, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. This model corresponds to the UDM1 (ubiquitin-dependent double-strand break [DSB] recruitment module 1) domain of RNF168, which comprises LRM1 (LR motif 1), UMI (ubiquitin-interacting motif [UIM]- and MIU-related UBD) and MIU1 (motif interacting with ubiquitin 1). Mutations of Ub-interacting residues in UDM1 have little effect on the accumulation of RNF168 to DSB sites, suggesting that it may not be the main site of binding ubiquitylated and polyubiquitylated targets.


Pssm-ID: 409018 [Multi-domain]  Cd Length: 73  Bit Score: 38.69  E-value: 1.90e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  691 EAARKAKQGKENlwkenlRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTL 746
Cdd:cd22265    19 EAERRALEEEEN------RASEEYIQKLLAEEEEEEKLAEERRRAEEEQLKEDEEL 68
PTZ00184 PTZ00184
calmodulin; Provisional
247-306 6.88e-03

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 38.97  E-value: 6.88e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062  247 KYRQKFNSLDKSMSGYLSGFQARNAL--LQSNLSQTQLATIWTLADIDGDGQLKAEEFILAM 306
Cdd:PTZ00184   85 EIKEAFKVFDRDGNGFISAAELRHVMtnLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
 
Name Accession Description Interval E-value
PH_13 pfam16652
Pleckstrin homology domain;
1412-1555 2.47e-85

Pleckstrin homology domain;


Pssm-ID: 465218  Cd Length: 143  Bit Score: 275.04  E-value: 2.47e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1412 VQCEGLAEQLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKT 1491
Cdd:pfam16652    1 VQCEGLSEQLVFNSLTNCLGPRKLLHSGKLYKVKSNKELVGFLFNDFLLLTQPVKPLS-SAGTDKLFSSKSNIQYKMYKT 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062  1492 PIFLNEVLVKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKKKRE 1555
Cdd:pfam16652   80 PIFLNEVMVKLPTDPSSSEPTFQLSHIDRVYTLKAESPNERTAWVKKIKEASELYIETEKKKRE 143
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
1555-1689 5.02e-82

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 265.02  E-value: 5.02e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1555 EKAYQARSQKTSGIGRLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCL 1634
Cdd:cd08375     1 EKAYLARSQRASGIGRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCI 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1635 TLFDRDQFSPDDFLGRTEIPVAKIRTE-QESKGPVTRRLLLHEVPTGEVWVRFDLQ 1689
Cdd:cd08375    81 TVFDRDFFSPDDFLGRTEIRVADILKEtKESKGPITKRLLLHEVPTGEVVVKLDLQ 136
PH_ITSN cd13264
Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in ...
1420-1552 1.69e-73

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270084  Cd Length: 132  Bit Score: 240.82  E-value: 1.69e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1420 QLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKTPIFLNEVL 1499
Cdd:cd13264     1 QLIFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQPIKPLG-SSGNDFVFDNKANIQYKMYKTPIFLNEVL 79
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1500 VKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKK 1552
Cdd:cd13264    80 VKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 132
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
1214-1394 6.53e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 160.93  E-value: 6.53e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1214 IHELIQTEERYMADLQLVVEVFQKRM-AESGFLTEGEMALIFVNWKELIMSNTKLLKALRVRKKTggEKMPVQMVGDILA 1292
Cdd:smart00325    2 LKELLQTERNYVRDLKLLVEVFLKPLkKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEE--WDDSVERIGDVFL 79
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1293 AELSHMQAYIRFCSCQLNGAALLQQKtDEDTDFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTPESH 1372
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158
                           170       180
                    ....*....|....*....|..
gi 966980062   1373 ADHSSLKLALERAEELCSQVNE 1394
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
1210-1393 7.89e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 160.54  E-value: 7.89e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1210 RQGYIHELIQTEERYMADLQLVVEVFQKRMAESG-FLTEGEMALIFVNWKELIMSNTKLLKALRVRKKTGGekMPVQMVG 1288
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELlPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1289 DILAAELSHMQAYIRFCSCQLNGAALLQQKTDEDTDFKEFLKKLasDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENT 1368
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156
                         170       180
                  ....*....|....*....|....*
gi 966980062 1369 PESHADHSSLKLALERAEELCSQVN 1393
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
1214-1393 5.18e-44

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 157.85  E-value: 5.18e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1214 IHELIQTEERYMADLQLVVEVFQKRMAESGFLTEGEMALIFVNWKELIMSNTKLLkaLRVRKKtggEKMPVQMVGDILAA 1293
Cdd:pfam00621    2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLK---EWISIQRIGDIFLK 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1294 ELSHMQAYIRFCSCQLNGAALLQQKTDEDTDFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTPESHA 1373
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156
                          170       180
                   ....*....|....*....|
gi 966980062  1374 DHSSLKLALERAEELCSQVN 1393
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
759-815 3.03e-37

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212921 [Multi-domain]  Cd Length: 57  Bit Score: 134.23  E-value: 3.03e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  759 LVNYRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11988     1 LVNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1130-1183 2.14e-35

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 128.95  E-value: 2.14e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11996     1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54
SH3_Intersectin2_4 cd11994
Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1057-1115 1.27e-34

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212927  Cd Length: 59  Bit Score: 126.58  E-value: 1.27e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARGKKRQKGWFPASHVKLL 1115
Cdd:cd11994     1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQARGKKRQKGWFPASHVKLL 59
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
15-107 3.31e-34

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 127.01  E-value: 3.31e-34
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062     15 MWAITSEERTKHDRQFDNLKPSG-GYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQGQ 93
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQdGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80
                            90
                    ....*....|....
gi 966980062     94 QLPVVLPPIMKQPP 107
Cdd:smart00027   81 PIPASLPPSLIPPS 94
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
902-953 4.91e-34

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 124.77  E-value: 4.91e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11990     1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
985-1036 6.27e-34

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212925  Cd Length: 52  Bit Score: 124.35  E-value: 6.27e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11992     1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVRP 52
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
985-1036 4.91e-31

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 116.36  E-value: 4.91e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11838     1 EYIALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
1131-1183 7.87e-31

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 115.59  E-value: 7.87e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11840     1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
1057-1114 1.18e-30

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 115.51  E-value: 1.18e-30
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARGKKRQKGWFPASHVKL 1114
Cdd:cd11839     1 IAQVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARGKKRQIGWFPANYVKL 58
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
762-815 1.26e-30

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 115.15  E-value: 1.26e-30
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11836     2 YRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANYVEK 55
SH3_Intersectin1_4 cd11993
Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1053-1117 1.24e-29

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212926  Cd Length: 65  Bit Score: 112.90  E-value: 1.24e-29
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1053 KKPEIAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARGKKRQKGWFPASHVKLLGP 1117
Cdd:cd11993     1 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSP 65
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
237-316 3.52e-29

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 112.37  E-value: 3.52e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062    237 EWAVPQPSRLKYRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLTDMAKAGQ 316
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
1571-1664 3.53e-27

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 107.15  E-value: 3.53e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKPNGKSNPYCEISMGS-QSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDFLG 1649
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFLG 80
                          90
                  ....*....|....*
gi 966980062 1650 RTEIPVAKIRTEQES 1664
Cdd:cd00030    81 EVEIPLSELLDSGKE 95
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1130-1183 4.65e-27

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 105.04  E-value: 4.65e-27
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11995     1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 54
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
902-953 3.08e-26

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 102.44  E-value: 3.08e-26
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGR-GWFPKSYVKI 953
Cdd:cd11837     1 TATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEGGEeGWFPKSYVKE 53
C2 pfam00168
C2 domain;
1569-1658 3.45e-26

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 104.32  E-value: 3.45e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  1569 GRLMVHVIEATELKACKPNGKSNPYCEISM--GSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDD 1646
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80
                           90
                   ....*....|..
gi 966980062  1647 FLGRTEIPVAKI 1658
Cdd:pfam00168   81 FIGEVRIPLSEL 92
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1570-1666 4.79e-25

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 101.02  E-value: 4.79e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1570 RLMVHVIEATELKACKPNGKSNPYCEISMG---SQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDD 1646
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80
                            90       100
                    ....*....|....*....|
gi 966980062   1647 FLGRTEIPVAKIRTEQESKG 1666
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEK 100
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
248-314 2.96e-24

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 97.29  E-value: 2.96e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  248 YRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLTDMAKA 314
Cdd:cd00052     1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
27-91 9.80e-24

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 95.75  E-value: 9.80e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   27 DRQFDNLKPSG-GYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQ 91
Cdd:cd00052     2 DQIFRSLDPDGdGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
985-1036 9.03e-23

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212924  Cd Length: 52  Bit Score: 92.74  E-value: 9.03e-23
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11991     1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52
SH3_Intersectin1_1 cd11987
First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
762-815 1.30e-22

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212920 [Multi-domain]  Cd Length: 55  Bit Score: 92.37  E-value: 1.30e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11987     2 YRALYPFEARSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 55
SH3_Intersectin1_2 cd11989
Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
902-953 3.52e-22

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212922 [Multi-domain]  Cd Length: 52  Bit Score: 90.93  E-value: 3.52e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11989     1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 52
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
1569-1682 6.71e-21

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 89.66  E-value: 6.71e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKAcKPN-------GKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQ 1641
Cdd:cd08391     1 GVLRIHVIEAQDLVA-KDKfvgglvkGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDP 79
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 966980062 1642 fSPDDFLGRTEIPVAKIRTEQESKGPVTrrllLHEVPTGEV 1682
Cdd:cd08391    80 -DKDDFLGRLSIDLGSVEKKGFIDEWLP----LEDVKSGRL 115
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
1569-1688 1.71e-20

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 89.02  E-value: 1.71e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATEL--KACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDD 1646
Cdd:cd04024     1 GVLRVHVVEAKDLaaKDRSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKD 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062 1647 FLGRTEIPVAKIRTEQESKGPVT------RRLLLHEVPTGEVWVRFDL 1688
Cdd:cd04024    81 YLGEFDIALEEVFADGKTGQSDKwitlksTRPGKTSVVSGEIHLQFSW 128
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
1128-1182 2.06e-20

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 86.05  E-value: 2.06e-20
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   1128 PVCQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN-GVTGLFPSNYVK 1182
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
1569-1659 7.27e-20

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 86.58  E-value: 7.27e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYqDVLCLTLFDRDQFSPDDFL 1648
Cdd:cd08377     1 GFLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIH-DVLEVTVYDEDKDKKPEFL 79
                          90
                  ....*....|.
gi 966980062 1649 GRTEIPVAKIR 1659
Cdd:cd08377    80 GKVAIPLLSIK 90
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
1131-1180 3.04e-19

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 82.51  E-value: 3.04e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN-GVTGLFPSNY 1180
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 51
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
1132-1181 5.01e-19

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 81.98  E-value: 5.01e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11826     2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 51
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
1131-1182 1.52e-18

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 80.75  E-value: 1.52e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
1134-1181 4.16e-18

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 79.31  E-value: 4.16e-18
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11823     4 ALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYV 51
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
1571-1663 3.19e-17

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 79.15  E-value: 3.19e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKPNGKSNPYCEISM-GSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDFLG 1649
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDLLG 80
                          90
                  ....*....|....
gi 966980062 1650 RTEIPVAKIRTEQE 1663
Cdd:cd04040    81 SAYIDLSDLEPEET 94
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
1568-1671 1.28e-16

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 78.52  E-value: 1.28e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1568 IGRLMVHVIEATELKACKPNGkSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLyQDVLCLTLFDRDQFSPDDF 1647
Cdd:cd04038     1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNP-MAPLKLEVFDKDTFSKDDS 78
                          90       100       110
                  ....*....|....*....|....*....|
gi 966980062 1648 LGRTEI------PVAKIRTEQESKGPVTRR 1671
Cdd:cd04038    79 MGEAEIdleplvEAAKLDHLRDTPGGTQIK 108
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
762-814 2.12e-16

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 74.50  E-value: 2.12e-16
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 966980062    762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 814
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKS--DDGWWKGRLGrGKEGLFPSNYVE 56
SH3_9 pfam14604
Variant SH3 domain;
1134-1182 2.93e-16

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 74.19  E-value: 2.93e-16
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 966980062  1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
1131-1182 7.29e-16

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 73.12  E-value: 7.29e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVK 52
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
1131-1182 7.37e-16

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 73.51  E-value: 7.37e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11972     4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVE 55
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
1134-1181 7.51e-16

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 73.10  E-value: 7.51e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11772     4 ALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
1133-1181 7.69e-16

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 73.16  E-value: 7.69e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKD-DPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11804     3 VAKHDFKATAEDELSFKKGSILKVLNMEdDPNWYKAELDGKEGLIPKNYI 52
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
982-1035 2.50e-15

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 71.80  E-value: 2.50e-15
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062    982 VGEEYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGD-RSGIFPSNYVK 1035
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKsDDGWWKGRLGRgKEGLFPSNYVE 56
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
1134-1182 2.85e-15

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 71.61  E-value: 2.85e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11875     4 VLFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNGKRGVFPDNFVE 54
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
762-814 3.98e-15

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 70.81  E-value: 3.98e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEG--GWWEGTLNGKTGWFPSNYVK 52
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
1129-1183 5.92e-15

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 70.57  E-value: 5.92e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062 1129 VCQViaMYDYAANNEDELSFSKGQLINVMNKDDPD--WWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12142     1 YCRV--LFDYNPVAPDELALKKGDVIEVISKETEDegWWEGELNGRRGFFPDNFVMP 55
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
1132-1182 6.40e-15

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 70.25  E-value: 6.40e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11949     2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
1132-1181 6.97e-15

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 70.21  E-value: 6.97e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11951     2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
1131-1186 8.37e-15

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 69.98  E-value: 8.37e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVkmTTD 1186
Cdd:cd11964     2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV--TAD 55
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
902-952 1.18e-14

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 69.87  E-value: 1.18e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 966980062    902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGR-GWFPKSYVK 952
Cdd:smart00326    4 QVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKGRLGRGKeGLFPSNYVE 56
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
1132-1181 1.33e-14

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 69.46  E-value: 1.33e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEI-NGVTGLFPSNYV 1181
Cdd:cd11812     2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLvNGQQGYFPANYV 52
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
1131-1182 2.37e-14

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 68.65  E-value: 2.37e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11820     2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
1131-1182 2.39e-14

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212904 [Multi-domain]  Cd Length: 59  Bit Score: 68.89  E-value: 2.39e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11971     1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
1133-1178 2.44e-14

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 68.38  E-value: 2.44e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966980062  1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE-INGVTGLFPS 1178
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRnKGGKEGLIPS 47
PTZ00121 PTZ00121
MAEBL; Provisional
346-756 3.07e-14

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 78.64  E-value: 3.07e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  346 SYQKIQEEEPQKKLpvtfEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKR 425
Cdd:PTZ00121 1298 AEEKKKADEAKKKA----EEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKK 1373
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  426 LEKQRELErqreeerrkeierreAAKQELERQRRLE------------WERIRRQELLNQKNRE----QEEIVRLNSKKK 489
Cdd:PTZ00121 1374 EEAKKKAD---------------AAKKKAEEKKKADeakkkaeedkkkADELKKAAAAKKKADEakkkAEEKKKADEAKK 1438
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  490 SLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCD--LEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKN 567
Cdd:PTZ00121 1439 KAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEeaKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKA 1518
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  568 MQFSNTPDSGVSLLHKKS--LEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFL 645
Cdd:PTZ00121 1519 EEAKKADEAKKAEEAKKAdeAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVM 1598
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  646 LLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKE-----NLWKENLRREEEEKQKRLQ 720
Cdd:PTZ00121 1599 KLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKaeeenKIKAAEEAKKAEEDKKKAE 1678
                         410       420       430
                  ....*....|....*....|....*....|....*..
gi 966980062  721 EEKTQEkiqEEERKAEEK-QRKDKDTLKVEEKQRETA 756
Cdd:PTZ00121 1679 EAKKAE---EDEKKAAEAlKKEAEEAKKAEELKKKEA 1712
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1130-1183 3.52e-14

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 68.39  E-value: 3.52e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1130 CQVIamYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12057     2 CKVL--FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKL 55
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
987-1035 3.74e-14

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 68.22  E-value: 3.74e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDG---EWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11842     3 VALYDFAGEQPGDLAFQKGDIITILKKSDsqnDWWTGRIGGREGIFPANYVE 54
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
1131-1182 4.16e-14

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 68.22  E-value: 4.16e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDP--DWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqnDWWTGRIGGREGIFPANYVE 54
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
1132-1182 4.28e-14

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 68.06  E-value: 4.28e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
986-1033 4.38e-14

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 67.87  E-value: 4.38e-14
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                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGD-RSGIFPSNY 1033
Cdd:cd00174     2 ARALYDYEAQDDDELSFKKGDIITVLEKdDDGWWEGELNGgREGLFPANY 51
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
1132-1182 5.43e-14

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 67.79  E-value: 5.43e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12061     2 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVR 52
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
1131-1181 5.69e-14

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 67.68  E-value: 5.69e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYV 51
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
1131-1182 7.05e-14

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 67.54  E-value: 7.05e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11950     1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
1131-1181 8.86e-14

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 67.05  E-value: 8.86e-14
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11827     1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYV 51
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
1128-1181 9.06e-14

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 67.28  E-value: 9.06e-14
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gi 966980062 1128 PVCQviAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11803     1 PCCR--ALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYV 52
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
1130-1183 9.47e-14

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 66.97  E-value: 9.47e-14
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                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIamYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11874     2 CKVL--FSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
762-812 1.11e-13

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 66.72  E-value: 1.11e-13
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gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN-FGWFPCNY 812
Cdd:cd00174     2 ARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGELNGGrEGLFPANY 51
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
1134-1178 1.69e-13

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 66.65  E-value: 1.69e-13
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPD----WWQGEINGVTGLFPS 1178
Cdd:cd11762     4 ALYDYEAQSDEELSFPEGAIIRILRKDDNGvddgWWEGEFNGRVGVFPS 52
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
902-950 1.80e-13

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 66.33  E-value: 1.80e-13
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGR-GWFPKSY 950
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDdDGWWEGELNGGReGLFPANY 51
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
1133-1183 1.80e-13

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 66.29  E-value: 1.80e-13
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11959     3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 53
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
988-1036 2.12e-13

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 66.11  E-value: 2.12e-13
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11805     4 ALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYVQP 53
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
1132-1183 2.73e-13

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 65.62  E-value: 2.73e-13
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gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
1131-1182 2.89e-13

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212815 [Multi-domain]  Cd Length: 54  Bit Score: 65.78  E-value: 2.89e-13
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLI-NVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11882     1 RARALYACKAEDESELSFEPGQIItNVQPSDEPGWLEGTLNGRTGLIPENYVE 53
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
1131-1186 2.90e-13

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 65.81  E-value: 2.90e-13
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVkmTTD 1186
Cdd:cd11963     3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV--TTD 56
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
1133-1182 2.93e-13

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 65.51  E-value: 2.93e-13
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVmNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11838     3 IALYPYESNEPGDLTFNAGDVILV-TKKDGEWWTGTIGDRTGIFPSNYVR 51
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
1129-1181 3.09e-13

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 65.63  E-value: 3.09e-13
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                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1129 VCQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11956     1 EVEAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYI 53
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
1132-1182 3.26e-13

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 65.43  E-value: 3.26e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLI-NVMnKDDPDWWQGEING-VTGLFPSNYVK 1182
Cdd:cd11825     2 VKALYDYRAQRPDELSFCKHAIItNVE-KEDGGWWRGDYGGkKQKWFPANYVE 53
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
902-954 3.45e-13

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 65.31  E-value: 3.45e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966980062   902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 954
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGRVGLVPSTAVEEI 54
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
1133-1182 3.65e-13

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 65.47  E-value: 3.65e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11824     3 SVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLE 52
DUF5401 pfam17380
Family of unknown function (DUF5401); This is a family of unknown function found in ...
335-754 4.40e-13

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.


Pssm-ID: 375164 [Multi-domain]  Cd Length: 722  Bit Score: 74.39  E-value: 4.40e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   335 KQIDSINGTLPSYQKIQ---EEEPQKKLPVTFEDKRKANYERGNM-ELEKRRQAL-VEQQQREAERKAQKEKEEWERKQR 409
Cdd:pfam17380  221 KEVQGMPHTLAPYEKMErrkESFNLAEDVTTMTPEYTVRYNGQTMtENEFLNQLLhIVQHQKAVSERQQQEKFEKMEQER 300
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   410 ELQEQEwKKQLELEKRleKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQKNR-EQEEIVRLNSKK 488
Cdd:pfam17380  301 LRQEKE-EKAREVERR--RKLEEAEKARQAEMDRQAAIYAEQERMAMERERELERIRQEERKRELERiRQEEIAMEISRM 377
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   489 KslhlELEALNGKHQQISGRLQ---DVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQnkliylvpEKQLLNERI 565
Cdd:pfam17380  378 R----ELERLQMERQQKNERVRqelEAARKVKILEEERQRKIQQQKVEMEQIRAEQEEARQRE--------VRRLEEERA 445
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   566 KNMQfsntpdsgvsLLHKKSLEKQELCQRLKEQldalEKETASKLSEMDsynnqlkcgnmddsvlqcllsllsclnnlfl 645
Cdd:pfam17380  446 REME----------RVRLEEQERQQQVERLRQQ----EEERKRKKLELE------------------------------- 480
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   646 llKELREtcntQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDeaaRKAKQGKENLWKENLRREEEEKQKRLQEEKTQ 725
Cdd:pfam17380  481 --KEKRD----RKRAEEQRRKILEKELEERKQAMIEEERKRKLLE---KEMEERQKAIYEEERRREAEEERRKQQEMEER 551
                          410       420
                   ....*....|....*....|....*....
gi 966980062   726 EKIQEEERKAEEKQRKdkdtLKVEEKQRE 754
Cdd:pfam17380  552 RRIQEQMRKATEERSR----LEAMERERE 576
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
1134-1183 4.40e-13

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 65.17  E-value: 4.40e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD-----DPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12059     4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYVTS 58
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
1570-1666 4.58e-13

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 67.51  E-value: 4.58e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDFLG 1649
Cdd:cd04025     1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80
                          90
                  ....*....|....*..
gi 966980062 1650 RTEIPVAKIRTEQESKG 1666
Cdd:cd04025    81 KVVFSIQTLQQAKQEEG 97
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
986-1036 4.76e-13

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 65.01  E-value: 4.76e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVT-QKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEGDLLYISdKSDPNWWKATCGGKTGLIPSNYVEE 53
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
1132-1182 4.80e-13

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 64.92  E-value: 4.80e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVE 52
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
763-814 5.62e-13

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 65.06  E-value: 5.62e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11823     3 KALYSYTANREDELSLQPGDIIEVHEK--QDDGWWLGELNGKKGIFPATYVE 52
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1131-1182 5.71e-13

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 64.92  E-value: 5.71e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12052     1 EAIVEFDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVR 52
SH3_9 pfam14604
Variant SH3 domain;
764-814 7.35e-13

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 64.56  E-value: 7.35e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 966980062   764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEES--EDGWWEGINTGRTGLVPANYVE 49
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
1133-1183 8.20e-13

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 64.26  E-value: 8.20e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN-GVTGLFPSNYVKM 1183
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAkGQKGLFPANYVEL 54
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
988-1035 9.07e-13

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212775  Cd Length: 54  Bit Score: 64.34  E-value: 9.07e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILV---TQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11841     4 ALYSFEGQQPCDLSFQAGDRITVltrTDSQFDWWEGRLRGRVGIFPANYVS 54
EF-hand_4 pfam12763
Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin ...
30-86 1.02e-12

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.


Pssm-ID: 289529  Cd Length: 104  Bit Score: 65.86  E-value: 1.02e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062    30 FDNLKPSGGYITGDQARNFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLI 86
Cdd:pfam12763   16 FSGLKPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLI 72
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
762-814 1.02e-12

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 64.24  E-value: 1.02e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEGDLLYISDKS--DPNWWKATCGGKTGLIPSNYVE 52
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
1134-1181 1.13e-12

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 64.07  E-value: 1.13e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD-----DPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDKVGIFPSNYV 56
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
1134-1181 1.24e-12

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 64.19  E-value: 1.24e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD-----DPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 56
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1132-1180 1.28e-12

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 63.87  E-value: 1.28e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEING---VTGLFPSNY 1180
Cdd:cd11821     2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGdpsRRGVFPVSF 53
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
1132-1181 1.37e-12

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 63.95  E-value: 1.37e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11806     2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1131-1183 1.52e-12

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212924  Cd Length: 52  Bit Score: 63.85  E-value: 1.52e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDpDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11991     1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDG-DWWTGTVGDKTGVFPSNYVRP 52
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
1132-1182 1.70e-12

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 63.87  E-value: 1.70e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12060     4 VKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
1131-1180 1.72e-12

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 63.37  E-value: 1.72e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNY 1180
Cdd:cd11845     1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARhlSTGKEGYIPSNY 52
EF-hand_4 pfam12763
Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin ...
247-311 1.86e-12

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.


Pssm-ID: 289529  Cd Length: 104  Bit Score: 65.09  E-value: 1.86e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   247 KYRQKFNSLdKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMHLT-DM 311
Cdd:pfam12763   11 KYWEIFSGL-KPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIfDL 75
PTZ00121 PTZ00121
MAEBL; Provisional
349-789 2.76e-12

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 72.48  E-value: 2.76e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  349 KIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQ--EQEWKKQLELEKRL 426
Cdd:PTZ00121 1348 AKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKADELKkaAAAKKKADEAKKKA 1427
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  427 EKQRELERQREEERRKEIERReaAKQELERQRRLE-----WERIRRQELLNQKNREQEEIVRLN-----SKKKSLHLELE 496
Cdd:PTZ00121 1428 EEKKKADEAKKKAEEAKKADE--AKKKAEEAKKAEeakkkAEEAKKADEAKKKAEEAKKADEAKkkaeeAKKKADEAKKA 1505
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  497 ALNGKHQQISGRLQDVRLKKQTQKTElevlDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTPDS 576
Cdd:PTZ00121 1506 AEAKKKADEAKKAEEAKKADEAKKAE----EAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALR 1581
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  577 GVSLLHKKSLEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKcgnMDDSVLQCLLSLLSCLNNLFLLLKELRETCNT 656
Cdd:PTZ00121 1582 KAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELK---KAEEEKKKVEQLKKKEAEEKKKAEELKKAEEE 1658
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  657 QQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKEnlwKENLRREEEEKQKRLQEEKTQEKIQ----EEE 732
Cdd:PTZ00121 1659 NKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKK---AEELKKKEAEEKKKAEELKKAEEENkikaEEA 1735
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  733 RKAEEKQRKDKDTLKVEEKQRETASVLVNYRALYPFEARNHDEMSFNSGdiiqVDEK 789
Cdd:PTZ00121 1736 KKEAEEDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEE----LDEE 1788
PTZ00121 PTZ00121
MAEBL; Provisional
352-759 3.76e-12

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 72.10  E-value: 3.76e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  352 EEEPQKKLPVTFEDKRKANYERGNMEL--EKRRQAlVEQQQREAERKAQK-EKEEWERKQRELQE--QEWKKQLELEKRL 426
Cdd:PTZ00121 1246 EEERNNEEIRKFEEARMAHFARRQAAIkaEEARKA-DELKKAEEKKKADEaKKAEEKKKADEAKKkaEEAKKADEAKKKA 1324
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  427 EKQRELERQREEERRKEIERREAAKQELERQRRlEWERIRRQELLNQKNREQEEIVRLNSKKKSLHL-ELEALNGKHQQI 505
Cdd:PTZ00121 1325 EEAKKKADAAKKKAEEAKKAAEAAKAEAEAAAD-EAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKkKADEAKKKAEED 1403
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  506 SGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTPDSG-------- 577
Cdd:PTZ00121 1404 KKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAkkkaeeak 1483
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  578 -VSLLHKKSLEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNT 656
Cdd:PTZ00121 1484 kADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEK 1563
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  657 QQlaLEQLYKIKRDK---------LKEIERKRLELIQK-----KKLEDEAARKAKQGKENlwKENLRREEEEKQK----- 717
Cdd:PTZ00121 1564 KK--AEEAKKAEEDKnmalrkaeeAKKAEEARIEEVMKlyeeeKKMKAEEAKKAEEAKIK--AEELKKAEEEKKKveqlk 1639
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  718 -------------RLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASVL 759
Cdd:PTZ00121 1640 kkeaeekkkaeelKKAEEENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEAL 1694
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
1132-1180 3.91e-12

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212712 [Multi-domain]  Cd Length: 51  Bit Score: 62.52  E-value: 3.91e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPD-WWQGEINGVTGLFPSNY 1180
Cdd:cd11778     2 VEALYDYEAQGDDEISIRVGDRIAVIRGDDGSgWTYGEINGVKGLFPTSY 51
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1132-1180 6.01e-12

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 61.73  E-value: 6.01e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
1132-1182 6.60e-12

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 61.94  E-value: 6.60e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNK--DDPDWWQGE-INGVTGLFPSNYVK 1182
Cdd:cd11767     2 VVALYPFTGENDEELSFEKGERLEIIEKpeDDPDWWKARnALGTTGLVPRNYVE 55
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
1129-1184 7.65e-12

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 61.77  E-value: 7.65e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1129 VCQViAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKMT 1184
Cdd:cd12073     1 ICAV-ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
1569-1672 8.11e-12

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 63.43  E-value: 8.11e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPN-GKSNPYCEISM---GSQSYTTRTIQDTLNPKWNfnCQFFIKDLYQDV-----LCLTLFDR 1639
Cdd:cd04041     1 GVLVVTIHRATDLPKADFGtGSSDPYVTASFakfGKPLYSTRIIRKDLNPVWE--ETWFVLVTPDEVkagerLSCRLWDS 78
                          90       100       110
                  ....*....|....*....|....*....|...
gi 966980062 1640 DQFSPDDFLGRTEIPVAKIrteQESKGPVTRRL 1672
Cdd:cd04041    79 DRFTADDRLGRVEIDLKEL---IEDRNWMGRRE 108
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
763-814 8.34e-12

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212815 [Multi-domain]  Cd Length: 54  Bit Score: 61.54  E-value: 8.34e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIqVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11882     3 RALYACKAEDESELSFEPGQII-TNVQPSDEPGWLEGTLNGRTGLIPENYVE 53
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
762-814 8.72e-12

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 61.60  E-value: 8.72e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFVE 54
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
762-815 8.84e-12

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212723 [Multi-domain]  Cd Length: 55  Bit Score: 61.56  E-value: 8.84e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVEK 815
Cdd:cd11789     2 YRAMYDYAAADDDEVSFQEGDVI-INVEIIDD-GWMEGTVQrtGQSGMLPANYVEL 55
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
987-1036 1.03e-11

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 61.28  E-value: 1.03e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKD-GEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11840     3 IALFPYTAQNEDELSFQKGDIINVLSKDdPDWWRGELNGQTGLFPSNYVEP 53
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
1131-1183 1.12e-11

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212879 [Multi-domain]  Cd Length: 56  Bit Score: 61.19  E-value: 1.12e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKD-DPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11946     2 EAIAKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIEM 55
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
1132-1180 1.19e-11

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 61.14  E-value: 1.19e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEING-----VTGLFPSNY 1180
Cdd:cd11883     2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISssgkvKRGWFPSNY 55
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
1545-1649 1.25e-11

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 64.65  E-value: 1.25e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1545 QYIDTEKkkrekaYQARSQKTSGIGRLMVHVIEATELKACKPNGKSNPYCEISM--GSQSYT---TRTIQDTLNPKWN-- 1617
Cdd:cd04020     9 KYVPPES------EGALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLlpDKSKKSkqkTPVVKKSVNPVWNht 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 966980062 1618 --FNcQFFIKDLYQDVLCLTLFDRDQFSPDDFLG 1649
Cdd:cd04020    83 fvYD-GVSPEDLSQACLELTVWDHDKLSSNDFLG 115
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
1134-1181 1.59e-11

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 60.99  E-value: 1.59e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd12056     6 ALFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNGKEGVFPDNFV 55
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
1568-1691 1.71e-11

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 62.96  E-value: 1.71e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1568 IGRLMVHVIEATELKAC-KPNGKSNPYCEISMGSQSYT--TRTIQDTLNPKWNfNCQFFIKDLYQDVLCLTLFDRDQFSP 1644
Cdd:cd04044     1 IGVLAVTIKSARGLKGSdIIGGTVDPYVTFSISNRRELarTKVKKDTSNPVWN-ETKYILVNSLTEPLNLTVYDFNDKRK 79
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062 1645 DDFLGRTEIPVAKIRTEQESKGpVTRRLLLHEVPTGEvwVRFDLQLF 1691
Cdd:cd04044    80 DKLIGTAEFDLSSLLQNPEQEN-LTKNLLRNGKPVGE--LNYDLRFF 123
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
987-1031 1.81e-11

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 60.29  E-value: 1.81e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966980062   987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTG-SIGDRSGIFPS 1031
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKsEDGWWKGrNKGGKEGLIPS 47
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
1571-1675 1.87e-11

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 63.14  E-value: 1.87e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKPNGKSNPYCEISM-------GSQSYTTRTIQDTLNPKWnfNCQFFIK-DLYQDVLCLTLFDRDQF 1642
Cdd:cd04033     2 LRVKVLAGIDLAKKDIFGASDPYVKISLydpdgngEIDSVQTKTIKKTLNPKW--NEEFFFRvNPREHRLLFEVFDENRL 79
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 966980062 1643 SPDDFLGRTEIPVAKIRTEQE--SKGPVTRRLLLH 1675
Cdd:cd04033    80 TRDDFLGQVEVPLNNLPTETPgnERRYTFKDYLLR 114
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
1133-1181 2.12e-11

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212743 [Multi-domain]  Cd Length: 53  Bit Score: 60.49  E-value: 2.12e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11809     3 TAQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYI 51
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
1132-1182 2.37e-11

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 60.24  E-value: 2.37e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEING-VTGLFPSNYVK 1182
Cdd:cd11969     2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGkVQHYFPSNYVE 53
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
763-814 2.58e-11

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 60.12  E-value: 2.58e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11840     3 IALFPYTAQNEDELSFQKGDIINVLSKD--DPDWWRGELNGQTGLFPSNYVE 52
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
1555-1664 2.92e-11

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 63.16  E-value: 2.92e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1555 EKAYQARSQKTSGIGRLMVHVIEATELKACKPNGKSNPYCEIS----------------MGSQS-------------YTT 1605
Cdd:cd08676    14 EALLERVREAEPPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGivpasrernsekskkrKSHRKkavlkdtvpaksiKVT 93
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1606 RTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDqfspDDFLGRTEIPVAKIRTEQES 1664
Cdd:cd08676    94 EVKPQTLNPVWNETFRFEVEDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSCGLD 148
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
1054-1113 2.92e-11

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 60.24  E-value: 2.92e-11
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   1054 KPEIAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELqargKKRQKGWFPASHVK 1113
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL----GRGKEGLFPSNYVE 56
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
1131-1182 3.09e-11

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 59.82  E-value: 3.09e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12046     1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
1132-1181 3.11e-11

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212837 [Multi-domain]  Cd Length: 57  Bit Score: 60.04  E-value: 3.11e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNK--DDPDWWQ-GEINGVTGLFPSNYV 1181
Cdd:cd11904     3 VQALYPFSSSNDEELNFEKGEVMDVIEKpeNDPEWWKcRKANGQVGLVPKNYV 55
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
1133-1182 3.25e-11

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 59.95  E-value: 3.25e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNK-DDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIYNKkGQQGWWRGEINGRIGWFPSTYVE 53
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
987-1036 3.43e-11

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212820 [Multi-domain]  Cd Length: 60  Bit Score: 60.05  E-value: 3.43e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTG----SIGDR-SGIFPSNYVKP 1036
Cdd:cd11887     5 KALYPYESDHEDDLNFDVGQLITVTEEeDADWYFGeyvdSNGNTkEGIFPKNFVEV 60
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
1057-1111 3.45e-11

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 59.78  E-value: 3.45e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQargkKRQKGWFPASH 1111
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELN----GGREGLFPANY 51
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
1133-1181 3.74e-11

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 59.68  E-value: 3.74e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd12006     4 VALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
1132-1181 4.00e-11

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212777 [Multi-domain]  Cd Length: 53  Bit Score: 59.74  E-value: 4.00e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVM-NKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11843     2 VRALYDYEGQESDELSFKAGDILTKLeEEDEQGWCKGRLDGRVGLYPANYV 52
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
452-739 5.04e-11

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 68.16  E-value: 5.04e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   452 QELERQ-RRLEWERIRRQELLNQKNREQE--------EIVRLNSKKKSLHLELEALNGKHQQISGRLQdvrlKKQTQKTE 522
Cdd:TIGR02168  196 NELERQlKSLERQAEKAERYKELKAELRElelallvlRLEELREELEELQEELKEAEEELEELTAELQ----ELEEKLEE 271
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   523 LEVLDKQCDLEIMEIKQLQQELQEYQNKliyLVPEKQLLNERIKNMQFSNTPDSGVSLLHKKSL-EKQELCQRLKEQLDA 601
Cdd:TIGR02168  272 LRLEVSELEEEIEELQKELYALANEISR---LEQQKQILRERLANLERQLEELEAQLEELESKLdELAEELAELEEKLEE 348
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   602 LEKETASKLSEMDSYNNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNTQQLALEQLYKIK--RDKLKEIERKR 679
Cdd:TIGR02168  349 LKEELESLEAELEELEAELE--ELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEdrRERLQQEIEEL 426
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062   680 LELIQKKKLEDEAARKA--KQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQ 739
Cdd:TIGR02168  427 LKKLEEAELKELQAELEelEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQ 488
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
1134-1182 5.21e-11

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 59.30  E-value: 5.21e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11786     4 ALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
763-813 5.24e-11

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 59.45  E-value: 5.24e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd12056     5 KALFHYEGTNEDELDFKEGEIILIISKDTGEPGWWKGELNGKEGVFPDNFV 55
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
1132-1182 5.41e-11

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212827  Cd Length: 56  Bit Score: 59.57  E-value: 5.41e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPD---WWQGEINGVTGLFPSNYVK 1182
Cdd:cd11894     2 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFNGRIGVFPSVLVE 55
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
1130-1182 6.93e-11

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 59.21  E-value: 6.93e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1130 CQViaMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12054     3 CKV--LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
1131-1182 7.16e-11

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212775  Cd Length: 54  Bit Score: 58.94  E-value: 7.16e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDP--DWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11841     1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRGRVGIFPANYVS 54
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
762-814 7.90e-11

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 58.81  E-value: 7.90e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11803     3 CRALYDFEPENEGELGFKEGDIItltnQIDEN------WYEGMVNGQSGFFPVNYVE 53
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
763-816 8.51e-11

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 58.93  E-value: 8.51e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd12061     3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTHNGRTGWFPSNYVREI 54
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
1569-1657 8.97e-11

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 61.11  E-value: 8.97e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISM---GSQSYT--TRTIQDTLNPKWNfncQFFI------KDLYQDVLCLTLF 1637
Cdd:cd04031    16 SQLIVTVLQARDLPPRDDGSLRNPYVKVYLlpdRSEKSKrrTKTVKKTLNPEWN---QTFEysnvrrETLKERTLEVTVW 92
                          90       100
                  ....*....|....*....|
gi 966980062 1638 DRDQFSPDDFLGRTEIPVAK 1657
Cdd:cd04031    93 DYDRDGENDFLGEVVIDLAD 112
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
377-771 9.36e-11

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 66.88  E-value: 9.36e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  377 ELEKRRQALveqqQREAErKAqkekeeweRKQRELQEQEwkKQLELEKRLekqrelerqreeerrkeierreaakqeler 456
Cdd:COG1196   197 ELERQLEPL----ERQAE-KA--------ERYRELKEEL--KELEAELLL------------------------------ 231
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  457 qRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIME 536
Cdd:COG1196   232 -LKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEER 310
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  537 IKQLQQelqeyqnkliylvpEKQLLNERIKnmqfsntpdsgvSLLHKKSLEKQELcQRLKEQLDALEKETASKLSEMDSY 616
Cdd:COG1196   311 RRELEE--------------RLEELEEELA------------ELEEELEELEEEL-EELEEELEEAEEELEEAEAELAEA 363
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  617 NNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELREtcntQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKA 696
Cdd:COG1196   364 EEALL--EAEAELAEAEEELEELAEELLEALRAAAE----LAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEE 437
                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  697 KQGKENLwkenLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASVLVNYRALYPFEAR 771
Cdd:COG1196   438 EEEEEAL----EEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLE 508
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1130-1182 9.72e-11

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 58.47  E-value: 9.72e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1130 CQViaMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12055     2 CQV--AFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 52
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
1131-1183 1.09e-10

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 58.53  E-value: 1.09e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDpDWWQGEINGVT-GLFPSNYVKM 1183
Cdd:cd11837     1 TATALYPWRAKKENHLSFAKGDIITVLEQQE-MWWFGELEGGEeGWFPKSYVKE 53
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
1057-1111 1.11e-10

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 58.45  E-value: 1.11e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARGKKRQKGWFPASH 1111
Cdd:cd11883     1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVKRGWFPSNY 55
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
1136-1181 1.21e-10

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 58.51  E-value: 1.21e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062 1136 YDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
348-755 1.35e-10

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 66.50  E-value: 1.35e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  348 QKIQEEEPQKKLpvtfEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKE------EWERKQRELQEQEWKKQLE 421
Cdd:COG1196   295 AELARLEQDIAR----LEERRRELEERLEELEEELAELEEELEELEEELEELEEEleeaeeELEEAEAELAEAEEALLEA 370
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  422 LEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGK 501
Cdd:COG1196   371 EAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEE 450
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  502 HQQISGRLQDVRLKKQTQKTELEVLDKQcdleimeikqlqqeLQEYQNKLIYLVPEKQLLNERIKNMQFsntPDSGVSLL 581
Cdd:COG1196   451 EAELEEEEEALLELLAELLEEAALLEAA--------------LAELLEELAEAAARLLLLLEAEADYEG---FLEGVKAA 513
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  582 HKKSLEK---------------------------------------QELCQRLKEQLDA------LEKETASKLSEMDSY 616
Cdd:COG1196   514 LLLAGLRglagavavligveaayeaaleaalaaalqnivveddevaAAAIEYLKAAKAGratflpLDKIRARAALAAALA 593
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  617 NNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKEL----RETCNTQQLALEQLYKIKRDKLKEIE-RKRLELIQKKKLEDE 691
Cdd:COG1196   594 RGAIGAAVDLVASDLREADARYYVLGDTLLGRTLvaarLEAALRRAVTLAGRLREVTLEGEGGSaGGSLTGGSRRELLAA 673
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062  692 AARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRET 755
Cdd:COG1196   674 LLEAEAELEELAERLAEEELELEEALLAEEEEERELAEAEEERLEEELEEEALEEQLEAEREEL 737
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
1207-1461 1.37e-10

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 66.45  E-value: 1.37e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1207 ERKRQGYIHELIQTEERYMADLQLVVEVFQKRMAESGFLTEGE----MALIFVNWKELIMSNTKLLKALRVRKKTggeKM 1282
Cdd:COG5422   482 EIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQCL---SP 558
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1283 PVQMVGDILAAELSHMQAYIRFCSCQLNGAALLQQKTDEDTDFKEF--LKKLASDPRCKGmpLSSFLLKPMQRITRYPLL 1360
Cdd:COG5422   559 IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFdhEVERLDESRKLE--LDGYLTKPTTRLARYPLL 636
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1361 IRSILENTPESHADHSSLKLALERAEELCSQVNEGVREKENsdRLEWIQahvqcegLAEQLIFNSLTNCLG----PRKLL 1436
Cdd:COG5422   637 LEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEN--RGDLFH-------LNQQLLFKPEYVNLGlndeYRKII 707
                         250       260       270
                  ....*....|....*....|....*....|..
gi 966980062 1437 HSGKLYKTKSNK-------ELHGFLFNDFLLL 1461
Cdd:COG5422   708 FKGVLKRKAKSKtdgslrgDIQFFLLDNMLLF 739
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
763-814 1.41e-10

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212817 [Multi-domain]  Cd Length: 56  Bit Score: 58.11  E-value: 1.41e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQV-DEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11884     3 VAVRAYITRDQTLLSFHKGDVIKLlPKEGPLDPGWLFGTLDGRSGAFPKEYVQ 55
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
1570-1688 1.42e-10

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 60.63  E-value: 1.42e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWN----FNcQFFI----KDLYQD--VLCLTLFDR 1639
Cdd:cd04017     2 QLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDqtliFD-EVELygspEEIAQNppLVVVELFDQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1640 DQFSPDDFLGRTEI-PVAKIRTEQESKGPvtrrLLLHEV-----PTGEVWVRFDL 1688
Cdd:cd04017    81 DSVGKDEFLGRSVAkPLVKLDLEEDFPPK----LQWFPIykggqSAGELLAAFEL 131
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
1131-1183 1.44e-10

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 58.12  E-value: 1.44e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1131 QVIAmyDYAANNEDELSFSKGQLINVMNKDDPDWWQGEING-----VTGLFPSNYVKM 1183
Cdd:cd11839     3 QVIA--PFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQArgkkrQIGWFPANYVKL 58
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
987-1034 1.53e-10

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 58.10  E-value: 1.53e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYV 1034
Cdd:cd11826     3 VALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
1131-1181 1.63e-10

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 58.11  E-value: 1.63e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPD-WWQGE-INGVTGLFPSNYV 1181
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGRnSRGEVGLFPSSYV 53
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1134-1180 1.66e-10

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 57.88  E-value: 1.66e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11818     4 ALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
1132-1181 1.70e-10

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212820 [Multi-domain]  Cd Length: 60  Bit Score: 58.12  E-value: 1.70e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEI---NGVT--GLFPSNYV 1181
Cdd:cd11887     4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYvdsNGNTkeGIFPKNFV 58
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
902-953 1.74e-10

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 57.71  E-value: 1.74e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEgGWWEGTLNGKTGWFPSNYVKE 53
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
762-815 1.93e-10

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 57.66  E-value: 1.93e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11766     2 AVVKFNYEAQREDELSLRKGDRVLVLEKS--SDGWWRGECNGQVGWFPSNYVTE 53
SMC_N pfam02463
RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...
341-750 2.21e-10

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.


Pssm-ID: 426784 [Multi-domain]  Cd Length: 1161  Bit Score: 65.76  E-value: 2.21e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   341 NGTLPSYQKIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQL 420
Cdd:pfam02463  625 VEGILKDTELTKLKESAKAKESGLRKGVSLEEGLAEKSEVKASLSELTKELLEIQELQEKAESELAKEEILRRQLEIKKK 704
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   421 ELEKRLEKQRELERQREEERRKEIERREAAKQELERQR------RLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLE 494
Cdd:pfam02463  705 EQREKEELKKLKLEAEELLADRVQEAQDKINEELKLLKqkideeEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTE 784
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   495 LEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTp 574
Cdd:pfam02463  785 KLKVEEEKEEKLKAQEEELRALEEELKEEAELLEEEQLLIEQEEKIKEEELEELALELKEEQKLEKLAEEELERLEEEI- 863
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   575 dsgvsLLHKKSLEKQELCQRLKEQLDALEKETASKLSEMDsynNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELREtc 654
Cdd:pfam02463  864 -----TKEELLQELLLKEEELEEQKLKDELESKEEKEKEE---KKELEEESQKLNLLEEKENEIEERIKEEAEILLKY-- 933
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   655 NTQQlalEQLYKIKRDKLKEIERKRLELIQKKKLEDEAarKAKQGKENLwkeNLRREEEEKQKRLQEEKTQEKIQEEERK 734
Cdd:pfam02463  934 EEEP---EELLLEEADEKEKEENNKEEEEERNKRLLLA--KEELGKVNL---MAIEEFEEKEERYNKDELEKERLEEEKK 1005
                          410
                   ....*....|....*.
gi 966980062   735 AEEKQRKDKDTLKVEE 750
Cdd:pfam02463 1006 KLIRAIIEETCQRLKE 1021
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
1132-1183 2.30e-10

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 57.41  E-value: 2.30e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG-EINGVTGLFPSNYVKM 1183
Cdd:cd11960     2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGtGPDGTYGLFPANYVEL 54
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
1131-1182 2.39e-10

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 57.26  E-value: 2.39e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11856     1 SYVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
1130-1182 2.40e-10

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 57.69  E-value: 2.40e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGL-FPSNYVK 1182
Cdd:cd11970     4 CAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 57
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
1134-1181 2.50e-10

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 57.37  E-value: 2.50e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDD--PDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11836     4 ALYAFEARNPDEISFQPGDIIQVDESQVaePGWLAGELKGKTGWFPANYV 53
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
1570-1690 2.53e-10

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 59.58  E-value: 2.53e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEISMGSQS---YTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFsPDD 1646
Cdd:cd04036     1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASdekKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 966980062 1647 FLGRTEIPVAKIRTEQeskgPVTRRLLLHEVPTGEVWVRFDLQL 1690
Cdd:cd04036    80 HLGTVLFDVSKLKLGE----KVRVTFSLNPQGKEELEVEFLLEL 119
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
1131-1183 2.55e-10

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212881 [Multi-domain]  Cd Length: 54  Bit Score: 57.52  E-value: 2.55e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMN-KDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11948     1 EAVALYSFQATESDELPFQKGDILKILNmEDDQNWYKAELQGREGYIPKNYIKV 54
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
903-953 2.62e-10

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 57.37  E-value: 2.62e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11786     2 AKALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYVQV 53
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
763-815 2.70e-10

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 57.42  E-value: 2.70e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11827     3 KALYAYDAQDTDELSFNEGDIIEILKEDPS--GWWTGRLRGKEGLFPGNYVEK 53
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
762-814 2.72e-10

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 57.48  E-value: 2.72e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12142     2 CRVLFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFVM 54
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
763-814 2.74e-10

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 57.35  E-value: 2.74e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIyirrQIDKN------WYEGEHNGRVGIFPASYVE 52
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
1133-1183 2.87e-10

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 57.35  E-value: 2.87e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 53
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
1573-1686 3.28e-10

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 59.39  E-value: 3.28e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1573 VHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLY-----QDVLCLTLFDRDQFSPDDF 1647
Cdd:cd08682     3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFELPGLLsgngnRATLQLTVMHRNLLGLDKF 82
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062 1648 LGRTEIPvakIRTEQESKG-PVTRRLLLHEVPT------GEVWVRF 1686
Cdd:cd08682    83 LGQVSIP---LNDLDEDKGrRRTRWFKLESKPGkddkerGEIEVDI 125
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
1134-1183 4.04e-10

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212862  Cd Length: 54  Bit Score: 56.87  E-value: 4.04e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11929     5 ALCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 54
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
1131-1183 4.12e-10

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212723 [Multi-domain]  Cd Length: 55  Bit Score: 56.94  E-value: 4.12e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLI-NVMNKDDpDWWQG--EINGVTGLFPSNYVKM 1183
Cdd:cd11789     1 RYRAMYDYAAADDDEVSFQEGDVIiNVEIIDD-GWMEGtvQRTGQSGMLPANYVEL 55
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
986-1036 4.25e-10

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 56.75  E-value: 4.25e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGE------WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11876     2 WTALFDYDARGEDELTLRRGQPVEVLSKDAAvsgdegWWTGKIGDKVGIFPSNYVAP 58
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
1569-1658 4.80e-10

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 58.75  E-value: 4.80e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISM-GSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQdVLCLTLFDRDQFSPDDF 1647
Cdd:cd04045     1 GVLRLHIRKANDLKNLEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPVTSPNQ-KITLEVMDYEKVGKDRS 79
                          90
                  ....*....|.
gi 966980062 1648 LGRTEIPVAKI 1658
Cdd:cd04045    80 LGSVEINVSDL 90
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
762-815 4.87e-10

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212714 [Multi-domain]  Cd Length: 55  Bit Score: 56.54  E-value: 4.87e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQ--GNFGWFPCNYVEK 815
Cdd:cd11780     2 YRALYSYTPQNEDELELREGDIVYVMEKC--DDGWFVGTSErtGLFGTFPGNYVAR 55
SH3_Nebulette_C cd11935
C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a ...
762-814 4.92e-10

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212868 [Multi-domain]  Cd Length: 58  Bit Score: 56.55  E-value: 4.92e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVE 814
Cdd:cd11935     3 YRAMYDYSAQDEDEVSFRDGDYI-VNVQPIDE-GWMYGTVQrtGRTGMLPANYIE 55
PTZ00121 PTZ00121
MAEBL; Provisional
364-754 5.14e-10

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 64.78  E-value: 5.14e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  364 EDKRKANYERGNMELEKRRQALVEQQQREAE--RKAQK-EKEEWERKQRELQE-QEWKKQLELEKRLEK-QRELERQREE 438
Cdd:PTZ00121 1179 EAARKAEEVRKAEELRKAEDARKAEAARKAEeeRKAEEaRKAEDAKKAEAVKKaEEAKKDAEEAKKAEEeRNNEEIRKFE 1258
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  439 ERRKEIERREAAKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEA--LNGKHQQISGRLQDVRLKK 516
Cdd:PTZ00121 1259 EARMAHFARRQAAIKAEEARKADELKKAEEKKKADEAKKAEEKKKADEAKKKAEEAKKAdeAKKKAEEAKKKADAAKKKA 1338
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  517 QTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLiylVPEKQLLNERIKNMQFSNTPDSgvslLHKKSLEKQELCQRLK 596
Cdd:PTZ00121 1339 EEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKK---EEAKKKADAAKKKAEEKKKADE----AKKKAEEDKKKADELK 1411
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  597 EQLDALEK-ETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNTQQLALEQLYKIKRDKLK-- 673
Cdd:PTZ00121 1412 KAAAAKKKaDEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKkk 1491
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  674 -EIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEkQRKDKDTLKVEEKQ 752
Cdd:PTZ00121 1492 aEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEE-LKKAEEKKKAEEAK 1570

                  ..
gi 966980062  753 RE 754
Cdd:PTZ00121 1571 KA 1572
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
763-815 5.20e-10

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 56.49  E-value: 5.20e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11976     3 KARYDFCARDRSELSLKEGDIIKILNKK-GQQGWWRGEIYGRVGWFPANYVEE 54
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
763-814 5.46e-10

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 56.18  E-value: 5.46e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11826     3 VALYDYTADKDDELSFQEGDIIYVTKKN--DDGWYEGVLNGVTGLFPGNYVE 52
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
905-951 5.85e-10

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 56.20  E-value: 5.85e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 951
Cdd:cd11823     4 ALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
1571-1663 5.88e-10

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 58.50  E-value: 5.88e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKPNGKSNPYCEISM---GSQSYTTRTIQDTLNPKWNFNCQF--F-IKDLYQDVLCLTLFDRDQFSP 1644
Cdd:cd08386    18 LTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFegFpYEKLQQRVLYLQVLDYDRFSR 97
                          90
                  ....*....|....*....
gi 966980062 1645 DDFLGRTEIPVAKIRTEQE 1663
Cdd:cd08386    98 NDPIGEVSLPLNKVDLTEE 116
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
762-816 6.05e-10

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212867 [Multi-domain]  Cd Length: 59  Bit Score: 56.54  E-value: 6.05e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVEKM 816
Cdd:cd11934     5 YRAVYDYNAADEDEVSFQDGDTI-VNVQQIDD-GWMYGTVErtGDTGMLPANYVEAI 59
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
1133-1181 6.40e-10

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 56.58  E-value: 6.40e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd12007     4 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 54
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
1570-1662 6.70e-10

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 58.44  E-value: 6.70e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEISM-GSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLcLTLFDRDQFSPDDFL 1648
Cdd:cd04042     1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPIEDVTQPLY-IKVFDYDRGLTDDFM 79
                          90
                  ....*....|....
gi 966980062 1649 GRTEIPVAKIRTEQ 1662
Cdd:cd04042    80 GSAFVDLSTLELNK 93
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
986-1034 7.10e-10

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212767 [Multi-domain]  Cd Length: 53  Bit Score: 55.97  E-value: 7.10e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11833     2 YVALYKFKPQENEDLEMRPGDKITLLDdSNEDWWKGKIEDRVGFFPANFV 51
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1133-1181 7.57e-10

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 55.88  E-value: 7.57e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11816     3 VARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51
SH3_RIM-BP_2 cd12012
Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs ...
1133-1182 7.61e-10

Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212945  Cd Length: 62  Bit Score: 56.15  E-value: 7.61e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1133 IAMYDYAANN--------EDELSFSKGQLINVMNKDDPD-WWQGEINGVTGLFPSNYVK 1182
Cdd:cd12012     3 VALFDYDPLTmspnpdaaEEELPFKEGQLIKVYGDKDADgFYLGEINGRRGLVPCNMVS 61
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
1132-1183 8.85e-10

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 55.85  E-value: 8.85e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11828     2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
1131-1180 8.96e-10

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 55.84  E-value: 8.96e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDD----PDWWQGEINGVTGLFPSNY 1180
Cdd:cd11800     1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDlkgnPEWWLVEDRGKQGYVPSNY 54
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
1575-1662 9.45e-10

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 57.65  E-value: 9.45e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1575 VIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDFLGRTEIP 1654
Cdd:cd08376     6 LVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEFIGRCEID 85

                  ....*...
gi 966980062 1655 VAKIRTEQ 1662
Cdd:cd08376    86 LSALPREQ 93
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
1131-1183 1.22e-09

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 55.46  E-value: 1.22e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPD---WWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11807     2 VVYALFDYEAENGDELSFREGDELTVLRKGDDDeteWWWARLNDKEGYVPRNLLGL 57
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
347-732 1.33e-09

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 63.42  E-value: 1.33e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  347 YQKIQEEEpqkklpvtfeDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRL 426
Cdd:COG1196   215 YRELKEEL----------KELEAELLLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELR-LELEELELEL 283
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  427 EKQRELERQREeerrkeierreAAKQELERQRRLEweRIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQIS 506
Cdd:COG1196   284 EEAQAEEYELL-----------AELARLEQDIARL--EERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAE 350
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  507 GRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQqelqeyqnkliylvpeKQLLNERiknmqfsntpdsgvsllhKKSL 586
Cdd:COG1196   351 EELEEAEAELAEAEEALLEAEAELAEAEEELEELA----------------EELLEAL------------------RAAA 396
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  587 EKQELCQRLKEQLDALEKETASKLSEmdsynnqlkcgnmddsvlqcllsllsclnnlflllkelRETCNTQQLALEQLYK 666
Cdd:COG1196   397 ELAAQLEELEEAEEALLERLERLEEE--------------------------------------LEELEEALAELEEEEE 438
                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  667 IKRDKLKEIERKRLELiQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEE 732
Cdd:COG1196   439 EEEEALEEAAEEEAEL-EEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADY 503
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
388-758 1.49e-09

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 63.15  E-value: 1.49e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   388 QQQREAERKAQKEKEEWERKQ---RELqeqewKKQLeleKRLEKQRElerqreeerrkeierreAAK--QELERQRR--- 459
Cdd:TIGR02168  172 ERRKETERKLERTRENLDRLEdilNEL-----ERQL---KSLERQAE-----------------KAEryKELKAELRele 226
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   460 -----LEWERIRRQ--ELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQcdl 532
Cdd:TIGR02168  227 lallvLRLEELREEleELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEISRLEQQ--- 303
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   533 eIMEIKqlqqelqeyqNKLIYLVPEKQLLNERIKNMQfsntpdsgvsllhKKSLEKQELCQRLKEQLDALEKETASKLSE 612
Cdd:TIGR02168  304 -KQILR----------ERLANLERQLEELEAQLEELE-------------SKLDELAEELAELEEKLEELKEELESLEAE 359
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   613 MDSYNNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNTQQLAleqlykikRDKLKEIERKRLELIQKKKLEDEA 692
Cdd:TIGR02168  360 LEELEAELE--ELESRLEELEEQLETLRSKVAQLELQIASLNNEIERL--------EARLERLEDRRERLQQEIEELLKK 429
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   693 ARKAKQGKENLWKENLRREEEEKQKRLqEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASV 758
Cdd:TIGR02168  430 LEEAELKELQAELEELEEELEELQEEL-ERLEEALEELREELEEAEQALDAAERELAQLQARLDSL 494
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
1134-1182 1.52e-09

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 55.34  E-value: 1.52e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPD-WWQGEINGVTGLFPSNYVK 1182
Cdd:cd11976     4 ARYDFCARDRSELSLKEGDIIKILNKKGQQgWWRGEIYGRVGWFPANYVE 53
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
1136-1181 1.61e-09

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 55.01  E-value: 1.61e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062 1136 YDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
902-951 1.69e-09

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 54.95  E-value: 1.69e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 951
Cdd:cd11964     2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDpNWWKGETPQGTGLFPSNFV 52
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
764-815 1.76e-09

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 54.94  E-value: 1.76e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKtIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11830     4 ARYDFCARDMRELSLKEGDVVKIYNK-KGQQGWWRGEINGRIGWFPSTYVEE 54
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
987-1033 1.91e-09

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 54.79  E-value: 1.91e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNY 1033
Cdd:cd11817     3 VALYDFTGETEEDLSFQRGDRILVTEHlDAEWSRGRLNGREGIFPRAF 50
DUF4670 pfam15709
Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins ...
336-524 1.94e-09

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.


Pssm-ID: 464815 [Multi-domain]  Cd Length: 522  Bit Score: 62.28  E-value: 1.94e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   336 QIDSINGTLPSYQKIQEEEPQKKLPVTFEdKRKANYERGNMELEKRRQALVEQQQREAE--RKAQKEKEEWERKQRELQE 413
Cdd:pfam15709  301 QTFVVTGNMESEEERSEEDPSKALLEKRE-QEKASRDRLRAERAEMRRLEVERKRREQEeqRRLQQEQLERAEKMREELE 379
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   414 QEWKKQLElEKRLEKQREL-ERQREEERRKEIERREAAKQELERQRRLEWERiRRQELlnQKNREQEEIVRLNSKKKSLH 492
Cdd:pfam15709  380 LEQQRRFE-EIRLRKQRLEeERQRQEEEERKQRLQLQAAQERARQQQEEFRR-KLQEL--QRKKQQEEAERAEAEKQRQK 455
                          170       180       190
                   ....*....|....*....|....*....|..
gi 966980062   493 LELEALNGKHQQISGRLQDVRLKKQTQKTELE 524
Cdd:pfam15709  456 ELEMQLAEEQKRLMEMAEEERLEYQRQKQEAE 487
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
988-1035 2.00e-09

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 54.68  E-value: 2.00e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11786     4 ALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYVQ 52
SMC_N pfam02463
RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...
376-758 2.13e-09

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.


Pssm-ID: 426784 [Multi-domain]  Cd Length: 1161  Bit Score: 62.68  E-value: 2.13e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   376 MELEKRRQALVEQQQREA-------ERKAQKEKEEWERKQrELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERRE 448
Cdd:pfam02463  169 RKKKEALKKLIEETENLAeliidleELKLQELKLKEQAKK-ALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLLQELLR 247
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   449 AAKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKhQQISGRLQDVRLKKQTQKTELEVLDK 528
Cdd:pfam02463  248 DEQEEIESSKQEIEKEEEKLAQVLKENKEEEKEKKLQEEELKLLAKEEEELKS-ELLKLERRKVDDEEKLKESEKEKKKA 326
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   529 QcdleiMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMqfsntpdsgvsllhkkSLEKQELCQRLKEQLDALEKETAS 608
Cdd:pfam02463  327 E-----KELKKEKEEIEELEKELKELEIKREAEEEEEEEL----------------EKLQEKLEQLEEELLAKKKLESER 385
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   609 KLSEMDSYNNQLKCGNMDDSVLQcllsllsclnnlflLLKELREtcntQQLALEQLYKIKRDKLKEIERKRLELIQKKKL 688
Cdd:pfam02463  386 LSSAAKLKEEELELKSEEEKEAQ--------------LLLELAR----QLEDLLKEEKKEELEILEEEEESIELKQGKLT 447
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   689 EDEAARKAKQGKENLWKENLRREEEEKQkRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASV 758
Cdd:pfam02463  448 EEKEELEKQELKLLKDELELKKSEDLLK-ETQLVKLQEQLELLLSRQKLEERSQKESKARSGLKVLLALI 516
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
762-816 2.52e-09

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212866 [Multi-domain]  Cd Length: 58  Bit Score: 54.63  E-value: 2.52e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVEKM 816
Cdd:cd11933     4 FRAMYDYRAADDDEVSFKDGDTI-VNVQTIDE-GWMYGTVQrtGKTGMLPANYVEAI 58
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
1592-1675 2.58e-09

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 56.93  E-value: 2.58e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1592 PYCEISM-GSQSYTTRTIQDTLNPKWNFNCQFFIKDlyQDVLCLTLFDRDQFSPDD--FLGRTEIPVAKIrteQESKGPV 1668
Cdd:cd08382    23 PFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVGP--SSIITIQVFDQKKFKKKDqgFLGCVRIRANAV---LPLKDTG 97

                  ....*..
gi 966980062 1669 TRRLLLH 1675
Cdd:cd08382    98 YQRLDLR 104
SH3_SH3RF1_1 cd11927
First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ...
1134-1183 2.63e-09

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212860  Cd Length: 54  Bit Score: 54.57  E-value: 2.63e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11927     5 ALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 54
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
762-813 2.63e-09

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 54.29  E-value: 2.63e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKtigEPGWLYGSFQ-GNFGWFPCNYV 813
Cdd:cd11837     2 ATALYPWRAKKENHLSFAKGDIITVLEQ---QEMWWFGELEgGEEGWFPKSYV 51
SH3_Lyn cd12004
Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of ...
987-1034 2.76e-09

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212937 [Multi-domain]  Cd Length: 56  Bit Score: 54.61  E-value: 2.76e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGS--IGDRSGIFPSNYV 1034
Cdd:cd12004     3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
763-814 2.82e-09

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212777 [Multi-domain]  Cd Length: 53  Bit Score: 54.35  E-value: 2.82e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQ--VDEKtigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11843     3 RALYDYEGQESDELSFKAGDILTklEEED---EQGWCKGRLDGRVGLYPANYVE 53
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
1134-1182 3.05e-09

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 54.25  E-value: 3.05e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11920     5 AVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 53
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
1133-1182 3.10e-09

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 54.26  E-value: 3.10e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPD-WWQGEINGVTGLFPSNYVK 1182
Cdd:cd11978     4 IARYDFCARDMRELSLLKGDVVKIYTKMSTNgWWRGEVNGRVGWFPSTYVE 54
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
988-1034 3.15e-09

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 54.34  E-value: 3.15e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYV 1034
Cdd:cd11827     4 ALYAYDAQDTDELSFNEGDIIEILKEDPSgWWTGRLRGKEGLFPGNYV 51
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
1134-1183 3.27e-09

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 54.35  E-value: 3.27e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1134 AMYDYAANNED--ELSFSKGQLINVmnKDDP-DWWQGEI-NGVTGLFPSNYVKM 1183
Cdd:cd11855     4 ALYPYDASPDDpnELSFEKGEILEV--SDTSgKWWQARKsNGETGICPSNYLQL 55
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
903-952 3.40e-09

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 54.07  E-value: 3.40e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11949     2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDpNWWKGACHGQTGMFPRNYVT 52
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
988-1034 3.47e-09

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 54.27  E-value: 3.47e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYV 1034
Cdd:cd11823     4 ALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
904-950 3.50e-09

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 54.21  E-value: 3.50e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGG-----RGWFPKSY 950
Cdd:cd11883     3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSgWWDGVIISSsgkvkRGWFPSNY 55
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
762-815 3.60e-09

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 54.18  E-value: 3.60e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11856     2 YVAIADYEAQGDDEISLQEGEVVEVLEK--NDSGWWYVRKGDKEGWVPASYLEP 53
SH3_Sla1p_2 cd11774
Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
1131-1181 3.71e-09

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212708 [Multi-domain]  Cd Length: 52  Bit Score: 54.01  E-value: 3.71e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT-GLFPSNYV 1181
Cdd:cd11774     1 QAKALYDYDKQTEEELSFNEGDTLDVYDDSDSDWILVGFNGTQfGFVPANYI 52
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
902-952 3.76e-09

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 54.17  E-value: 3.76e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYVQ 52
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
986-1036 3.88e-09

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 53.91  E-value: 3.88e-09
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSI-GDRSGIFPSNYVKP 1036
Cdd:cd11837     2 ATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELeGGEEGWFPKSYVKE 53
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
763-810 3.97e-09

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 53.75  E-value: 3.97e-09
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                   ....*....|....*....|....*....|....*....|....*....
gi 966980062   763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYG-SFQGNFGWFPC 810
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKS--EDGWWKGrNKGGKEGLIPS 47
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
1573-1653 4.25e-09

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 56.02  E-value: 4.25e-09
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gi 966980062 1573 VHVIEATELKACKPNGKSNPYCEISMGSQSYTTR--TIQDTLNPKwnFNCQFFIK-DLYQD-VLCLTLFDRDQFSPDDFL 1648
Cdd:cd04037     4 VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRdnYIPNTLNPV--FGKMFELEaTLPGNsILKISVMDYDLLGSDDLI 81

                  ....*
gi 966980062 1649 GRTEI 1653
Cdd:cd04037    82 GETVI 86
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
763-814 4.29e-09

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 54.06  E-value: 4.29e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11950     3 RALYDFEALEDDELGFNSGDVIEVLDSS--NPSWWKGRLHGKLGLFPANYVA 52
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
902-953 4.35e-09

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212747  Cd Length: 53  Bit Score: 54.04  E-value: 4.35e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11813     1 RAKALLDFERHDDDELGFRKNDIITIISQKdEHCWVGELNGLRGWFPAKFVEL 53
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
902-953 4.35e-09

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 54.01  E-value: 4.35e-09
                          10        20        30        40        50
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11820     2 KVRALYDFEAAEDNELTFKAGEIITVLDDSdPNWWKGSNHRGEGLFPANFVTA 54
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
1134-1181 4.46e-09

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 54.20  E-value: 4.46e-09
                          10        20        30        40        50
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gi 966980062 1134 AMYDYA-ANNEDELSFSKGQLINVMNKDDP-----DWWQGEI-NGVTGLFPSNYV 1181
Cdd:cd11771     4 ALYDFTpENPEMELSLKKGDIVAVLSKTDPlgrdsEWWKGRTrDGRIGWFPSNYV 58
SH3_Stac2_C cd11985
C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); ...
986-1035 4.75e-09

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212918  Cd Length: 53  Bit Score: 53.80  E-value: 4.75e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11985     2 YVALYKFLPQENNDLPLQPGDRVMVVDDSNEdWWKGKSGDRVGFFPANFVQ 52
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
1131-1181 4.84e-09

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212730  Cd Length: 51  Bit Score: 53.51  E-value: 4.84e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11796     1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
1133-1183 4.91e-09

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 53.65  E-value: 4.91e-09
                          10        20        30        40        50
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE-INGVTGLFPSNYVKM 1183
Cdd:cd11962     3 VVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTnSKGESGLFPSNYVEL 54
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
1131-1182 4.92e-09

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 53.82  E-value: 4.92e-09
                          10        20        30        40        50
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG-EINGVTGLFPSNYVK 1182
Cdd:cd11768     1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRArDKNGNEGYIPSNYVT 53
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
1570-1686 5.38e-09

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 55.81  E-value: 5.38e-09
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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFI---KDLYQDVLCLTLFDRDQFSP-D 1645
Cdd:cd04022     1 KLVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVsdpSRLSNLVLEVYVYNDRRSGRrR 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 966980062 1646 DFLGRTEIPVAKIRTEQESKG---PVTRRLLLHEVpTGEVWVRF 1686
Cdd:cd04022    81 SFLGRVRISGTSFVPPSEAVVqryPLEKRGLFSRV-RGEIGLKV 123
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
1134-1180 5.49e-09

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 53.58  E-value: 5.49e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT-------GLFPSNY 1180
Cdd:cd11773     4 ALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKVKLKVNSsdddepvGLVPATY 57
SH3_GRAP2_N cd11947
N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
1134-1181 5.62e-09

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212880 [Multi-domain]  Cd Length: 52  Bit Score: 53.65  E-value: 5.62e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDpDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11947     4 GKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFV 50
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
763-818 5.80e-09

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 53.85  E-value: 5.80e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEktIGEPGWLYGSFQGNFGWFPCNYVEKMPS 818
Cdd:cd12060     5 KARFNFKQTNEDELSVCKGDIIYVTR--VEEGGWWEGTLNGKTGWFPSNYVREIKS 58
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
1570-1665 5.86e-09

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 55.75  E-value: 5.86e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEI-----SMGSQSYTTRTIQDTLNPKWNFNCQFF---IKDLYQDVLCLTLFDRDQ 1641
Cdd:cd04035    16 ALHCTIIRAKGLKAMDANGLSDPYVKLnllpgASKATKLRTKTVHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLDEDR 95
                          90       100
                  ....*....|....*....|....
gi 966980062 1642 FSpDDFLGRTEIPVAKIRTEQESK 1665
Cdd:cd04035    96 FG-NDFLGETRIPLKKLKPNQTKQ 118
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
1059-1112 5.87e-09

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 53.62  E-value: 5.87e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1059 QVTSAYVASGSEQLSLAPGQLILILKKNT--SGWWQGELQARgkkrqKGWFPASHV 1112
Cdd:cd12142     3 RVLFDYNPVAPDELALKKGDVIEVISKETedEGWWEGELNGR-----RGFFPDNFV 53
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
985-1035 6.09e-09

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 53.42  E-value: 6.09e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11873     1 EVIVEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52
SH3_Stac3_1 cd11986
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 ...
986-1034 6.94e-09

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212919 [Multi-domain]  Cd Length: 53  Bit Score: 53.37  E-value: 6.94e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11986     2 FVALYRFKALEKDDLDFHPGERITVIDdSNEEWWRGKIGEKTGYFPMNFI 51
SH3_srGAP1-3 cd11955
Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called ...
1131-1181 7.19e-09

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212888 [Multi-domain]  Cd Length: 53  Bit Score: 53.41  E-value: 7.19e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11955     1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYI 51
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
986-1036 7.38e-09

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 53.28  E-value: 7.38e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGEWW------TGsigdRSGIFPSNYVKP 1036
Cdd:cd12009     2 VIAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWlaksltTG----KEGYIPSNYVAR 54
SH3_MPP cd11862
Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) ...
1134-1178 7.67e-09

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212796  Cd Length: 61  Bit Score: 53.35  E-value: 7.67e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1134 AMYDYAANNEDE-------LSFSKGQLINVMNKDDPDWWQ----GEINGVTGLFPS 1178
Cdd:cd11862     4 ALFDYDPEEDPLipckeagLSFKKGDILQIVNQDDPNWWQarkvGDPNGRAGLIPS 59
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
988-1036 7.73e-09

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 53.12  E-value: 7.73e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE---WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11875     4 VLFDYEAENEDELTLREGDIVTILSKDCEdkgWWKGELNGKRGVFPDNFVEP 55
SH3_Noxa1_C cd12047
C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox ...
1131-1181 7.99e-09

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212980  Cd Length: 53  Bit Score: 53.28  E-value: 7.99e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd12047     1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
1133-1182 8.24e-09

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212798  Cd Length: 58  Bit Score: 53.02  E-value: 8.24e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKD----DPDWWQGEINGVT-GLFPSNYVK 1182
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprVRGWLLATVDGQKiGLVPANYVK 57
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
1058-1112 8.28e-09

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212727 [Multi-domain]  Cd Length: 55  Bit Score: 53.11  E-value: 8.28e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGElqaRGKKRQKGWFPASHV 1112
Cdd:cd11793     2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGE---RLRDGERGWFPSSYT 53
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
988-1036 8.31e-09

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 53.09  E-value: 8.31e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11877     4 AKFNFEGTNEDELSFDKGDIITVTQVvEGGWWEGTLNGKTGWFPSNYVKE 53
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
1131-1182 9.19e-09

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212986  Cd Length: 56  Bit Score: 52.92  E-value: 9.19e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLI-NVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12053     1 EYIVEYDYDAVHEDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVK 53
SH3_GRAF2 cd12065
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also ...
763-814 9.41e-09

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212998 [Multi-domain]  Cd Length: 54  Bit Score: 53.07  E-value: 9.41e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQvDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12065     3 KAVYPCEAEHSSELSFEVGAIFE-DVTLSREPGWLEGTLNGKRGLIPENYVE 53
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
988-1034 1.05e-08

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 52.65  E-value: 1.05e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11803     5 ALYDFEPENEGELGFKEGDIItLTNQIDENWYEGMVNGQSGFFPVNYV 52
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
762-813 1.06e-08

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 53.02  E-value: 1.06e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd12058     2 WTALYDYEASGEDELSLRRGDVVEVlsqDAAVSGDDGWWAGKIRHRLGIFPANYV 56
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
1132-1182 1.11e-08

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212724 [Multi-domain]  Cd Length: 64  Bit Score: 53.10  E-value: 1.11e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPD-----WWQG--EINGVTGLFPSNYVK 1182
Cdd:cd11790     5 VRATHDYTAEDTDELTFEKGDVILVIPFDDPEeqdegWLMGvkESTGCRGVFPENFTE 62
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
1131-1182 1.21e-08

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 52.74  E-value: 1.21e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11782     1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
905-952 1.30e-08

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 52.42  E-value: 1.30e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11840     4 ALFPYTAQNEDELSFQKGDIINVLSKDDpDWWRGELNGQTGLFPSNYVE 52
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
1131-1182 1.54e-08

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212930 [Multi-domain]  Cd Length: 56  Bit Score: 52.27  E-value: 1.54e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKG-QLINVMNKDDPDWWQGEI-NGVTGLFPSNYVK 1182
Cdd:cd11997     3 RVRALYDYTGQEADELSFKAGeELLKIGEEDEQGWCKGRLlSGRIGLYPANYVE 56
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
347-621 1.70e-08

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 59.69  E-value: 1.70e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   347 YQKIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRqalVEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRL 426
Cdd:TIGR02168  215 YKELKAELRELELALLVLRLEELREELEELQEELKE---AEEELEELTAELQELEEKLEELRLEVSELE-EEIEELQKEL 290
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   427 EkqrelerqreeerrkeierreAAKQELER-QRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEA-------L 498
Cdd:TIGR02168  291 Y---------------------ALANEISRlEQQKQILRERLANLERQLEELEAQLEELESKLDELAEELAEleekleeL 349
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   499 NGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTpdsgv 578
Cdd:TIGR02168  350 KEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEDRRERLQQEIE----- 424
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 966980062   579 slLHKKSLEKQELcQRLKEQLDALEKETASKLSEMDSYNNQLK 621
Cdd:TIGR02168  425 --ELLKKLEEAEL-KELQAELEELEEELEELQEELERLEEALE 464
SH3_Alpha_Spectrin cd11808
Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red ...
1132-1182 1.82e-08

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212742 [Multi-domain]  Cd Length: 53  Bit Score: 52.10  E-value: 1.82e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11808     2 VVALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYVK 52
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
764-815 1.87e-08

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212910 [Multi-domain]  Cd Length: 58  Bit Score: 52.32  E-value: 1.87e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11977     5 ARYNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVEE 56
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1131-1181 2.07e-08

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 51.88  E-value: 2.07e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEING---VTGLFPSNYV 1181
Cdd:cd11966     1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGeptRRGAFPVSFV 54
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
988-1033 2.10e-08

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 51.93  E-value: 2.10e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVT-QKDGEWWTGSI---GDRSGIFPSNY 1033
Cdd:cd11821     4 ALYDCQADNDDELTFSEGEIIVVTgEEDDEWWEGHIegdPSRRGVFPVSF 53
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
988-1036 2.12e-08

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 51.75  E-value: 2.12e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11950     4 ALYDFEALEDDELGFNSGDVIEVLDSsNPSWWKGRLHGKLGLFPANYVAP 53
PTZ00121 PTZ00121
MAEBL; Provisional
349-753 2.16e-08

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 59.38  E-value: 2.16e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  349 KIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRQAlveQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEK 428
Cdd:PTZ00121 1110 KAEEARKAEEAKKKAEDARKAEEARKAEDARKAEEA---RKAEDAKRVEIARKAEDARKAEEARKAEDAKKAEAARKAEE 1186
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  429 QRELERQREEERRKEIERREAAKQE--LERQRRLEWER----IRRQELLNQKNRE--QEEIVRLNSKKKSLHlELEALNG 500
Cdd:PTZ00121 1187 VRKAEELRKAEDARKAEAARKAEEErkAEEARKAEDAKkaeaVKKAEEAKKDAEEakKAEEERNNEEIRKFE-EARMAHF 1265
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  501 KHQQISGRLQDVRLKKQTQKTElevldkqcdleimEIKQLQQELQEYqnkliylvpEKQLLNERIKNMQFSNTPDSgvsl 580
Cdd:PTZ00121 1266 ARRQAAIKAEEARKADELKKAE-------------EKKKADEAKKAE---------EKKKADEAKKKAEEAKKADE---- 1319
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  581 LHKKSLEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNnlflllKELRETCNTQQLA 660
Cdd:PTZ00121 1320 AKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKA------DAAKKKAEEKKKA 1393
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  661 LEQLYKIKRDKLKEIERKRLEliQKKKLEDEAARKAKQGKEnlwKENLRREEEEKQKRLQEEKTQE---KIQEEERKAEE 737
Cdd:PTZ00121 1394 DEAKKKAEEDKKKADELKKAA--AAKKKADEAKKKAEEKKK---ADEAKKKAEEAKKADEAKKKAEeakKAEEAKKKAEE 1468
                         410
                  ....*....|....*.
gi 966980062  738 KQRKDKDTLKVEEKQR 753
Cdd:PTZ00121 1469 AKKADEAKKKAEEAKK 1484
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
985-1035 2.17e-08

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 51.91  E-value: 2.17e-08
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gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDG-EWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11996     2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVK 53
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
986-1036 2.30e-08

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 52.08  E-value: 2.30e-08
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGE------WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd12059     2 WTAVFDYEASAEDELTLRRGDRVEVLSKDSAvsgdegWWTGKINDRVGIFPSNYVTS 58
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
763-814 2.34e-08

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 51.93  E-value: 2.34e-08
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gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEktigepGWLYGSF-QGNFGWFPCNYVE 814
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIItqieQIDE------GWWLGVNaKGQKGLFPANYVE 53
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
902-951 2.40e-08

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 51.94  E-value: 2.40e-08
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 951
Cdd:cd11963     3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDaNWWKGENHRGVGLFPSNFV 53
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
1064-1112 2.43e-08

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 51.62  E-value: 2.43e-08
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gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHV 1112
Cdd:cd11806     8 FVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNG-----CCGYIPASHL 51
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
763-814 2.54e-08

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 51.82  E-value: 2.54e-08
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVK 54
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
763-815 2.56e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 51.47  E-value: 2.56e-08
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11805     3 QALYDFNPQEPGELEFRRGDIITVLDSS--DPDWWKGELRGRVGIFPANYVQP 53
SH3_Eve1_2 cd11815
Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1133-1182 2.76e-08

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212749 [Multi-domain]  Cd Length: 52  Bit Score: 51.41  E-value: 2.76e-08
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11815     3 VVLHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGIFPANHVK 52
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
1134-1183 2.82e-08

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212747  Cd Length: 53  Bit Score: 51.73  E-value: 2.82e-08
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11813     4 ALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1569-1669 2.90e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 59.00  E-value: 2.90e-08
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gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGSQS-YTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDF 1647
Cdd:COG5038  1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSvYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDL 1119
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gi 966980062 1648 LGRTEIPVAKIRTEQE--SKGPVT 1669
Cdd:COG5038  1120 LGTAEIDLSKLEPGGTtnSNIPLD 1143
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
758-816 3.04e-08

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212724 [Multi-domain]  Cd Length: 64  Bit Score: 51.94  E-value: 3.04e-08
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gi 966980062  758 VLVNYRALYPFEARNHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGN--FGWFPCNYVEKM 816
Cdd:cd11790     1 VLYKVRATHDYTAEDTDELTFEKGDVILVipfDDPEEQDEGWLMGVKESTgcRGVFPENFTERI 64
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
763-814 3.25e-08

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 51.51  E-value: 3.25e-08
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gi 966980062  763 RALYPFEARNHD-EMSFNSGDIIQVDEKT--IGEP-GWLYGSFQ-GNFGWFPCNYVE 814
Cdd:cd11771     3 RALYDFTPENPEmELSLKKGDIVAVLSKTdpLGRDsEWWKGRTRdGRIGWFPSNYVE 59
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
1134-1182 3.41e-08

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212714 [Multi-domain]  Cd Length: 55  Bit Score: 51.53  E-value: 3.41e-08
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG--EINGVTGLFPSNYVK 1182
Cdd:cd11780     4 ALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGtsERTGLFGTFPGNYVA 54
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
1569-1663 3.47e-08

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 53.42  E-value: 3.47e-08
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gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISM---GSQSYTTRTIQDTLNPKwnFNCQFFIKDLYQDV----LCLTLFDRDQ 1641
Cdd:cd08385    16 NQLTVGIIQAADLPAMDMGGTSDPYVKVYLlpdKKKKFETKVHRKTLNPV--FNETFTFKVPYSELgnktLVFSVYDFDR 93
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gi 966980062 1642 FSPDDFLGRTEIPVAKIRTEQE 1663
Cdd:cd08385    94 FSKHDLIGEVRVPLLTVDLGHV 115
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1131-1183 3.51e-08

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212898 [Multi-domain]  Cd Length: 57  Bit Score: 51.55  E-value: 3.51e-08
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGV---TGLFPSNYVKM 1183
Cdd:cd11965     1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 56
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
762-815 3.56e-08

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 51.19  E-value: 3.56e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIgePGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12076     3 YTVIYPYTARDQDEINLEKGAVVEVIQKNL--EGWWKIRYQGKEGWAPASYLKK 54
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
763-814 3.78e-08

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 51.25  E-value: 3.78e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEktigepGWLYGSFQ-GNFGWFPCNYVE 814
Cdd:cd11960     3 RALYDYQAADDTEISFDPGDIItdieQIDE------GWWRGTGPdGTYGLFPANYVE 53
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
1132-1181 3.79e-08

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212817 [Multi-domain]  Cd Length: 56  Bit Score: 51.17  E-value: 3.79e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNK---DDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11884     2 VVAVRAYITRDQTLLSFHKGDVIKLLPKegpLDPGWLFGTLDGRSGAFPKEYV 54
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
903-952 3.87e-08

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 51.37  E-value: 3.87e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEfVDDDWWLGECHGSRGLFPSNYVE 52
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
903-954 3.99e-08

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 51.11  E-value: 3.99e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 954
Cdd:cd11803     3 CRALYDFEPENEGELGFKEGDIITLTNQiDENWYEGMVNGQSGFFPVNYVEVL 55
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
1569-1686 4.06e-08

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 53.02  E-value: 4.06e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELkackPN----GKSNPYCEISMGSQSYTTRTI----QdtlNPKWNFNCQFFIKDLYQDVLCLTLFDrD 1640
Cdd:cd08681     1 GTLVVVVLKARNL----PNkrklDKQDPYCVLRIGGVTKKTKTDfrggQ---HPEWDEELRFEITEDKKPILKVAVFD-D 72
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062 1641 QFSPDDFLGRTEIPVAKIRTEQESKGPVTrrLLLHEVPTGEVWVRF 1686
Cdd:cd08681    73 DKRKPDLIGDTEVDLSPALKEGEFDDWYE--LTLKGRYAGEVYLEL 116
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
1573-1656 4.25e-08

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 53.44  E-value: 4.25e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1573 VHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLcLTLFDRDQFSpDDFLGRTE 1652
Cdd:cd04046     7 VHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIK-IQVWNSNLLC-DEFLGQAT 84

                  ....
gi 966980062 1653 IPVA 1656
Cdd:cd04046    85 LSAD 88
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
1134-1183 4.32e-08

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 51.08  E-value: 4.32e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11928     5 ALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 54
PTZ00121 PTZ00121
MAEBL; Provisional
348-762 4.45e-08

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 58.61  E-value: 4.45e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  348 QKIQEEEPQKKLPVTFEDKRKANYERGNMElEKRRQALVEQQQREAERKAQK-EKEEWERKQRELQE-QEWKKQLELEKR 425
Cdd:PTZ00121 1464 KKAEEAKKADEAKKKAEEAKKADEAKKKAE-EAKKKADEAKKAAEAKKKADEaKKAEEAKKADEAKKaEEAKKADEAKKA 1542
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  426 LEKQRELERQREEERRKEIERREAAKQELERQRRLEWERiRRQELLNQKNREQEEIVRLNSKKKSLHLElEALNGKHQQI 505
Cdd:PTZ00121 1543 EEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALR-KAEEAKKAEEARIEEVMKLYEEEKKMKAE-EAKKAEEAKI 1620
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  506 sgRLQDVRlKKQTQKTELEVLDKQcdlEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQfsntpdsgvsllhkkS 585
Cdd:PTZ00121 1621 --KAEELK-KAEEEKKKVEQLKKK---EAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAE---------------E 1679
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  586 LEKQELCQRLKEQLDALEKETASKLSEMDSynnqlkcgnmddsvlqcllsllsclnnlflllKELRETCNTQQLAleqly 665
Cdd:PTZ00121 1680 AKKAEEDEKKAAEALKKEAEEAKKAEELKK--------------------------------KEAEEKKKAEELK----- 1722
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  666 kikrdklKEIERKRLELIQKKKLEDEAARKAkqgkenlwkENLRREEEEKQKRLQEEKTQEKIQEEERKAE----EKQRK 741
Cdd:PTZ00121 1723 -------KAEEENKIKAEEAKKEAEEDKKKA---------EEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKeaviEEELD 1786
                         410       420
                  ....*....|....*....|.
gi 966980062  742 DKDTLKVEEKQRETASVLVNY 762
Cdd:PTZ00121 1787 EEDEKRRMEVDKKIKDIFDNF 1807
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
1569-1681 4.56e-08

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 53.11  E-value: 4.56e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDT-LNPKWNFNCQFFIKDLYQDV---LCLTLFDRDQFSP 1644
Cdd:cd04049     1 GTLEVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDgRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKDNFSD 80
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 966980062 1645 DDFLGRTEIPVAKIRTEQESKGpvtrrlLLHEVPTGE 1681
Cdd:cd04049    81 DDFIGEATIHLKGLFEEGVEPG------TAELVPAKY 111
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
1132-1181 4.70e-08

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 50.97  E-value: 4.70e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMnKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd12009     2 VIAQYDFVPSNERDLQLKKGEKLQVL-KSDGEWWLAKslTTGKEGYIPSNYV 52
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
1588-1682 4.72e-08

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 52.60  E-value: 4.72e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1588 GKSNPYCEISMGSQS-YTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDrDQFSPDDFLGRTEIPVAKI--RTEQes 1664
Cdd:cd04052    11 GLLSPYAELYLNGKLvYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKD-DRDRHDPVLGSVSISLNDLidATSV-- 87
                          90
                  ....*....|....*...
gi 966980062 1665 kgpVTRRLLLHEVPTGEV 1682
Cdd:cd04052    88 ---GQQWFPLSGNGQGRI 102
SH3_p67phox-like_C cd11870
C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; ...
1131-1182 4.88e-08

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212803 [Multi-domain]  Cd Length: 53  Bit Score: 50.99  E-value: 4.88e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11870     1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
988-1035 4.99e-08

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 50.99  E-value: 4.99e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11961     4 ALYDYDAAEDNELSFFENDKIInIEFVDDDWWLGECHGSRGLFPSNYVE 52
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
985-1036 5.21e-08

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 50.71  E-value: 5.21e-08
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gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11856     1 SYVAIADYEAQGDDEISLQEGEVVEVLEKnDSGWWYVRKGDKEGWVPASYLEP 53
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
988-1036 5.57e-08

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 50.57  E-value: 5.57e-08
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11951     4 AQYDFSAEDPSQLSFRRGDIIEVLDCpDPNWWRGRISGRVGFFPRNYVHP 53
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
1133-1181 6.02e-08

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212941 [Multi-domain]  Cd Length: 56  Bit Score: 50.88  E-value: 6.02e-08
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd12008     3 VALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHslTTGQTGYIPSNYV 53
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
763-815 6.19e-08

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212713 [Multi-domain]  Cd Length: 57  Bit Score: 50.78  E-value: 6.19e-08
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVdekTIGEP--GWLYGSFQGN--FGWFPCNYVEK 815
Cdd:cd11779     4 KALYPHAAGGETQLSFEEGDVITL---LGPEPrdGWHYGENERSgrRGWFPIAYTEP 57
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
905-951 6.79e-08

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 50.59  E-value: 6.79e-08
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gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGE-VHGGRGWFPKSYV 951
Cdd:cd11812     4 ALYDYTANRSDELTIHRGDIIRVLYKdNDNWWFGSlVNGQQGYFPANYV 52
SH3_Sorbs1_3 cd11916
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), ...
759-814 6.80e-08

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212849 [Multi-domain]  Cd Length: 59  Bit Score: 50.76  E-value: 6.80e-08
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gi 966980062  759 LVNYRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN--FGWFPCNYVE 814
Cdd:cd11916     1 AYSYQALYSYAPQNDDELELRDGDIVDVMEKC--DDGWFVGTSRRTkqFGTFPGNYVK 56
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
988-1036 6.93e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 50.61  E-value: 6.93e-08
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11949     4 ALFDFDPQEDGELGFRRGDFIeVMDNSDPNWWKGACHGQTGMFPRNYVTP 53
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
1132-1180 7.04e-08

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 50.70  E-value: 7.04e-08
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gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11952     3 VYALWDYSAEFPDELSFKEGDMVTVLRKDgeGTDWWWASLCGREGYVPRNY 53
SH3_PACSIN1-2 cd11998
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) ...
1131-1182 7.14e-08

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212931 [Multi-domain]  Cd Length: 56  Bit Score: 50.72  E-value: 7.14e-08
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKG-QLINVMNKDDPDWWQGEI-NGVTGLFPSNYVK 1182
Cdd:cd11998     2 RVRALYDYDGQEQDELSFKAGdELTKLEDEDEQGWCKGRLdSGQVGLYPANYVE 55
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
1063-1109 7.20e-08

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 50.28  E-value: 7.20e-08
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gi 966980062  1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELqargKKRQKGWFPA 1109
Cdd:pfam00018    5 DYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRN----KGGKEGLIPS 47
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
904-952 7.63e-08

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 50.31  E-value: 7.63e-08
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gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11928     4 KALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQ 53
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
1569-1649 7.81e-08

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 52.74  E-value: 7.81e-08
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gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEIS----MGSQS-YTTRTIQDTLNPKWNFNCQFFIK--DLYQDVLCLTLFDRDQ 1641
Cdd:cd08384    13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYlkpdAGKKSkHKTQVKKKTLNPEFNEEFFYDIKhsDLAKKTLEITVWDKDI 92

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gi 966980062 1642 FSPDDFLG 1649
Cdd:cd08384    93 GKSNDYIG 100
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
763-814 7.95e-08

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 50.44  E-value: 7.95e-08
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gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11786     3 KALYNYEGKEPGDLSFKKGDIIllrkRIDEN------WYHGECNGKQGFFPASYVQ 52
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
1569-1658 8.47e-08

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 52.41  E-value: 8.47e-08
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gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISM---GSQSYTTRTIQDTLNPKW--NFNCQFFIKDLYQDVLCLTLFDRDQFS 1643
Cdd:cd08387    16 GILNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIHKKTLNPEFdeSFVFEVPPQELPKRTLEVLLYDFDQFS 95
                          90
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gi 966980062 1644 PDDFLGRTEIPVAKI 1658
Cdd:cd08387    96 RDECIGVVELPLAEV 110
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
764-813 8.48e-08

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 50.20  E-value: 8.48e-08
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gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVlskDAAVSGDEGWWTGKIGDKVGIFPSNYV 56
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
1134-1182 8.75e-08

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212867 [Multi-domain]  Cd Length: 59  Bit Score: 50.38  E-value: 8.75e-08
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG--EINGVTGLFPSNYVK 1182
Cdd:cd11934     7 AVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGtvERTGDTGMLPANYVE 57
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
986-1035 9.51e-08

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 50.01  E-value: 9.51e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWW-TGSIGDRSGIFPSNYVK 1035
Cdd:cd11849     2 YRALYDFKSAEPNTLSFSEGETFLLLERsNAHWWlVTNHSGETGYVPANYVK 53
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
1131-1182 1.00e-07

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 49.99  E-value: 1.00e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMN-KDDPDWWQGE-INGVTGLFPSNYVK 1182
Cdd:cd11769     3 ECIAKYNFNGASEEDLPFKKGDILTIVAvTKDPNWYKAKnKDGREGMIPANYVQ 56
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
988-1035 1.01e-07

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 50.16  E-value: 1.01e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11820     5 ALYDFEAAEDNELTFKAGEIITVLDdSDPNWWKGSNHRGEGLFPANFVT 53
SH3_Nebulette_C cd11935
C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a ...
1134-1183 1.01e-07

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212868 [Multi-domain]  Cd Length: 58  Bit Score: 50.00  E-value: 1.01e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEI--NGVTGLFPSNYVKM 1183
Cdd:cd11935     5 AMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
988-1034 1.03e-07

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 50.02  E-value: 1.03e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILV-TQKDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11963     6 ALYDFEAVEDNELTFKHGEIIIVlDDSDANWWKGENHRGVGLFPSNFV 53
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
1571-1659 1.07e-07

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 52.37  E-value: 1.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELkACKPNGKSNPYCEISMG----SQSYTTRTIQDTLNPKWNFNcqfFIKDLYQD---------------- 1630
Cdd:cd08675     1 LSVRVLECRDL-ALKSNGTCDPFARVTLNysskTDTKRTKVKKKTNNPRFDEA---FYFELTIGfsyekksfkveeedle 76
                          90       100       110
                  ....*....|....*....|....*....|.
gi 966980062 1631 --VLCLTLFDRDQFSPDDFLGRTEIPVAKIR 1659
Cdd:cd08675    77 ksELRVELWHASMVSGDDFLGEVRIPLQGLQ 107
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
909-953 1.07e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 49.95  E-value: 1.07e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062  909 WTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11995     9 YTAQNDDELAFSKGQIINVLNKEDpDWWKGELNGQVGLFPSNYVKL 54
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
1132-1181 1.10e-07

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 50.05  E-value: 1.10e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE-INGVTGLFPSNYV 1181
Cdd:cd11758     3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARnSEGKTGMIPVPYV 53
SH3_Sorbs1_3 cd11916
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), ...
1134-1183 1.12e-07

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212849 [Multi-domain]  Cd Length: 59  Bit Score: 49.99  E-value: 1.12e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT--GLFPSNYVKM 1183
Cdd:cd11916     6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSRRTKqfGTFPGNYVKL 57
SH3_Tks_2 cd12016
Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
762-815 1.16e-07

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212949  Cd Length: 54  Bit Score: 49.76  E-value: 1.16e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIgePGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12016     3 YITTQAYKAENEDEIGFETGVVVEVIQKNL--DGWWKIRYQGKEGWAPATYLKK 54
SH3_p40phox cd11869
Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil ...
1134-1183 1.17e-07

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212802  Cd Length: 54  Bit Score: 49.80  E-value: 1.17e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11869     4 ALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKI 53
SMC_N pfam02463
RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...
351-754 1.26e-07

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.


Pssm-ID: 426784 [Multi-domain]  Cd Length: 1161  Bit Score: 56.90  E-value: 1.26e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   351 QEEEPQKKLPVTFEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQR 430
Cdd:pfam02463  342 KELKELEIKREAEEEEEEELEKLQEKLEQLEEELLAKKKLESERLSSAAKLKEEELELKSEEEKEAQLLLELARQLEDLL 421
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   431 ELERQREEERRKEIERreaAKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALN----------- 499
Cdd:pfam02463  422 KEEKKEELEILEEEEE---SIELKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQEQLElllsrqkleer 498
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   500 -----------------------GKHQQISGRLQDVRLKKQTQK----TELEVLDKQCDLEIMEIKQLQQELQEYQNKLI 552
Cdd:pfam02463  499 sqkeskarsglkvllalikdgvgGRIISAHGRLGDLGVAVENYKvaisTAVIVEVSATADEVEERQKLVRALTELPLGAR 578
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   553 YLVPEKQLL-NERIKNMQFSNTPDSGVSLLHKKSLEKQE-------LCQRLKEQLDALEKETASKLSEMDSYNNQLKCGN 624
Cdd:pfam02463  579 KLRLLIPKLkLPLKSIAVLEIDPILNLAQLDKATLEADEddkrakvVEGILKDTELTKLKESAKAKESGLRKGVSLEEGL 658
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   625 MDDSVLQCLLSLLSCLNNLFLLLKELRETCNT-------------QQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDE 691
Cdd:pfam02463  659 AEKSEVKASLSELTKELLEIQELQEKAESELAkeeilrrqleikkKEQREKEELKKLKLEAEELLADRVQEAQDKINEEL 738
                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062   692 AARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQ----RKDKDTLKVEEKQRE 754
Cdd:pfam02463  739 KLLKQKIDEEEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKLkveeEKEEKLKAQEEELRA 805
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
764-814 1.29e-07

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 49.72  E-value: 1.29e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11959     4 ALYDYQAADDDEISFDPDDII-TNIEMIDE-GWWRGVCRGKYGLFPANYVE 52
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
1134-1181 1.29e-07

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 49.74  E-value: 1.29e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNK--DDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11866     4 GLWDCSGNEPDELSFKRGDLIYIISKeyDSFGWWVGELNGKVGLVPKDYL 53
SH3_SH3RF1_1 cd11927
First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ...
988-1035 1.29e-07

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212860  Cd Length: 54  Bit Score: 49.56  E-value: 1.29e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILV-TQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11927     5 ALYNYEGKEPGDLKFSKGDIIILrRQVDENWYHGEVNGIHGFFPTNFVQ 53
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
987-1036 1.41e-07

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 49.42  E-value: 1.41e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd12046     3 VALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVED 53
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
1133-1182 1.45e-07

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212910 [Multi-domain]  Cd Length: 58  Bit Score: 49.63  E-value: 1.45e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNK--DDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11977     4 VARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETNGRIGWFPSTYVE 55
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
1134-1182 1.45e-07

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212866 [Multi-domain]  Cd Length: 58  Bit Score: 49.62  E-value: 1.45e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN--GVTGLFPSNYVK 1182
Cdd:cd11933     6 AMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQrtGKTGMLPANYVE 56
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
902-953 1.51e-07

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212862  Cd Length: 54  Bit Score: 49.55  E-value: 1.51e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11929     2 RAKALCNYRGHNPGDLKFNKGDVILLRRQlDENWYLGEINGVSGIFPASSVEV 54
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
1133-1181 1.53e-07

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212767 [Multi-domain]  Cd Length: 53  Bit Score: 49.42  E-value: 1.53e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11833     3 VALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
763-815 1.55e-07

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 49.39  E-value: 1.55e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11820     4 RALYDFEAAEDNELTFKAGEIITVLDDS--DPNWWKGSNHRGEGLFPANFVTA 54
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
902-951 1.56e-07

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 49.66  E-value: 1.56e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 951
Cdd:cd11836     1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAepgWLAGELKGKTGWFPANYV 53
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
1131-1181 1.68e-07

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212727 [Multi-domain]  Cd Length: 55  Bit Score: 49.26  E-value: 1.68e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd11793     1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYT 53
SH3_Nck2_3 cd11903
Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
1132-1181 1.72e-07

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212836 [Multi-domain]  Cd Length: 59  Bit Score: 49.67  E-value: 1.72e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNK--DDPDWWQGE-INGVTGLFPSNYV 1181
Cdd:cd11903     3 VQTLYPFSSVTEEELNFEKGETMEVIEKpeNDPEWWKCKnSRGQVGLVPKNYV 55
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
763-814 1.72e-07

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 49.34  E-value: 1.72e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11842     3 VALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVE 54
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
902-951 1.84e-07

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 49.19  E-value: 1.84e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 951
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDgWWRGECNGQVGWFPSNYV 51
PTZ00121 PTZ00121
MAEBL; Provisional
352-753 1.88e-07

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 56.30  E-value: 1.88e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  352 EEEPQKKLPVTFEDKRKAnyergnmelEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKqre 431
Cdd:PTZ00121 1149 EDAKRVEIARKAEDARKA---------EEARKAEDAKKAEAARKAEEVRKAEELRKAEDARKAEAARKAEEERKAEE--- 1216
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  432 LERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRlqd 511
Cdd:PTZ00121 1217 ARKAEDAKKAEAVKKAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIKAEEARKADELKKAEEKKKAD--- 1293
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  512 vRLKKQTQKTELEVLDKQCD--LEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTPDSGVSLLHKKSLEKQ 589
Cdd:PTZ00121 1294 -EAKKAEEKKKADEAKKKAEeaKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKK 1372
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  590 ElcQRLKEQLDALEK---------ETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNTQQL- 659
Cdd:PTZ00121 1373 K--EEAKKKADAAKKkaeekkkadEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAk 1450
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  660 -ALEQLYKIKRDKLKEIERKRLELIQKKKLE----DEAARKAKQGKENlwKENLRREEEEKQKRLQEEKTQEKIQEEERK 734
Cdd:PTZ00121 1451 kKAEEAKKAEEAKKKAEEAKKADEAKKKAEEakkaDEAKKKAEEAKKK--ADEAKKAAEAKKKADEAKKAEEAKKADEAK 1528
                         410
                  ....*....|....*....
gi 966980062  735 AEEKQRKDKDTLKVEEKQR 753
Cdd:PTZ00121 1529 KAEEAKKADEAKKAEEKKK 1547
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
987-1035 1.92e-07

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 49.23  E-value: 1.92e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTG--SIGDRsGIFPSNYVK 1035
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIITqIEQIDEGWWLGvnAKGQK-GLFPANYVE 53
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
1063-1112 1.93e-07

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 49.26  E-value: 1.93e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELqaRGKkrqKGWFPASHV 1112
Cdd:cd11823     7 SYTANREDELSLQPGDIIEVHEKQDDGWWLGEL--NGK---KGIFPATYV 51
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
988-1034 1.99e-07

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212822  Cd Length: 53  Bit Score: 49.03  E-value: 1.99e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGS-IGDR-SGIFPSNYV 1034
Cdd:cd11889     4 AVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKlRRNGaEGIFPSNFV 53
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
377-742 2.02e-07

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 56.22  E-value: 2.02e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   377 ELEKRRQALVEQQQREAErkAQKEKEEWERKQRELQEQEWKKQLELEkRLEKQRElerqreeerrkeierreAAKQELER 456
Cdd:TIGR02168  678 EIEELEEKIEELEEKIAE--LEKALAELRKELEELEEELEQLRKELE-ELSRQIS-----------------ALRKDLAR 737
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   457 QRRleweriRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIME 536
Cdd:TIGR02168  738 LEA------EVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAE 811
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   537 IKQLQQELQEYQNKLIYLVPEKQLLNERIKNM--QFSNTPDSGVSLlhKKSLEK-QELCQRLKEQLDALEKETASKLSEM 613
Cdd:TIGR02168  812 LTLLNEEAANLRERLESLERRIAATERRLEDLeeQIEELSEDIESL--AAEIEElEELIEELESELEALLNERASLEEAL 889
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   614 DSYNNQLkcGNMDDSVLQCLLSLLSCLNnlflLLKELRETCNTQQLALEQLyKIKRDKLKEIERKRLELiqkkkLEDEAA 693
Cdd:TIGR02168  890 ALLRSEL--EELSEELRELESKRSELRR----ELEELREKLAQLELRLEGL-EVRIDNLQERLSEEYSL-----TLEEAE 957
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062   694 RKAKQgkenlwKENLRREEEEKQKRLQEEKTQ------EKIQEEErkaEEKQRKD 742
Cdd:TIGR02168  958 ALENK------IEDDEEEARRRLKRLENKIKElgpvnlAAIEEYE---ELKERYD 1003
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
986-1033 2.08e-07

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 49.12  E-value: 2.08e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWW------TGsigdRSGIFPSNY 1033
Cdd:cd11845     2 YVALYDYEARTDDDLSFKKGDRLQILDDsDGDWWlarhlsTG----KEGYIPSNY 52
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
1569-1658 2.12e-07

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 51.49  E-value: 2.12e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISM-----GSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDV-LCLTLFDRDQF 1642
Cdd:cd04026    13 NKLTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRrLSIEVWDWDRT 92
                          90
                  ....*....|....*.
gi 966980062 1643 SPDDFLGRTEIPVAKI 1658
Cdd:cd04026    93 TRNDFMGSLSFGVSEL 108
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
989-1035 2.24e-07

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 49.13  E-value: 2.24e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  989 LYPYSSVEPGDLTFTEGEEILVTQK---DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12057     5 LFPYEAQNEDELTIKEGDIVTLISKdciDAGWWEGELNGRRGVFPDNFVK 54
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
763-814 2.27e-07

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 48.93  E-value: 2.27e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIG--EPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11762     3 RALYDYEAQSDEELSFPEGAIIRILRKDDNgvDDGWWEGEFNGRVGVFPSLVVE 56
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
1060-1113 2.29e-07

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 48.79  E-value: 2.29e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1060 VTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGElqargKKRQKGWFPASHVK 1113
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVR-----KGDKEGWVPASYLE 52
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
988-1033 2.35e-07

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 49.16  E-value: 2.35e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE---WWTGSIGDRSGIFPSNY 1033
Cdd:cd11952     5 ALWDYSAEFPDELSFKEGDMVTVLRKDGEgtdWWWASLCGREGYVPRNY 53
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
1068-1112 2.35e-07

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 49.05  E-value: 2.35e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 966980062 1068 GSEQLSLAPGQLILILKKNTSGWWQGElqargKKRQKGWFPASHV 1112
Cdd:cd11829    13 HQQGLSFEAGELIRVLQAPDGGWWEGE-----KDGLRGWFPASYV 52
SH3_9 pfam14604
Variant SH3 domain;
988-1035 2.36e-07

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 48.77  E-value: 2.36e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 966980062   988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYVK 1035
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDgWWEGINTGRTGLVPANYVE 49
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
904-947 2.40e-07

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 48.74  E-value: 2.40e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 966980062   904 QALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGR-GWFP 947
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEdGWWKGRNKGGKeGLIP 46
SH3_Stac3_1 cd11986
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 ...
1133-1181 2.63e-07

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212919 [Multi-domain]  Cd Length: 53  Bit Score: 48.75  E-value: 2.63e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11986     3 VALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
764-813 2.66e-07

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 48.99  E-value: 2.66e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd12059     4 AVFDYEASAEDELTLRRGDRVEVlskDSAVSGDEGWWTGKINDRVGIFPSNYV 56
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
1134-1183 3.02e-07

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212778  Cd Length: 56  Bit Score: 48.88  E-value: 3.02e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPD---WWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11844     4 ALYDNVAESPDELAFRRGDILTVLEQNTAGlegWWLCSLRGRQGIAPGNRLKL 56
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
903-952 3.04e-07

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 48.48  E-value: 3.04e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIIT-VLEQQENWWFGEVHGGR-GWFPKSYVK 952
Cdd:cd11825     2 VKALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKKqKWFPANYVE 53
SH3_9 pfam14604
Variant SH3 domain;
905-952 3.04e-07

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 48.38  E-value: 3.04e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 966980062   905 ALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 952
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDgWWEGINTGRTGLVPANYVE 49
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
764-814 3.14e-07

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212727 [Multi-domain]  Cd Length: 55  Bit Score: 48.49  E-value: 3.14e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYVE 814
Cdd:cd11793     4 CVHAYTAQQPDELTLEEGDVVNVLRKM--PDGWYEGErlRDGERGWFPSSYTE 54
SH3_p67phox-like_C cd11870
C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; ...
987-1036 3.14e-07

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212803 [Multi-domain]  Cd Length: 53  Bit Score: 48.68  E-value: 3.14e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILV-TQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11870     3 VALHRYEAQGPEDLGFREGDTIDVlSEVNEAWLEGHSDGRVGIFPKCFVVP 53
SH3_ASPP1 cd11954
Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates ...
1132-1179 3.35e-07

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212887 [Multi-domain]  Cd Length: 57  Bit Score: 48.86  E-value: 3.35e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDD---PDWWQGEINGVTGLFPSN 1179
Cdd:cd11954     3 VYALWDYEAQNADELSFQEGDAITILRRKDdseTEWWWARLNDKEGYVPKN 53
SH3_PACSIN1-2 cd11998
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) ...
760-814 3.46e-07

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212931 [Multi-domain]  Cd Length: 56  Bit Score: 48.79  E-value: 3.46e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  760 VNYRALYPFEARNHDEMSFNSGD-IIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 814
Cdd:cd11998     1 VRVRALYDYDGQEQDELSFKAGDeLTKLEDED--EQGWCKGRLDsGQVGLYPANYVE 55
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
374-551 3.52e-07

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 55.46  E-value: 3.52e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   374 GNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQE-----QEWKKQLE-LEKRLEKQRELERQREEERRKEIERR 447
Cdd:TIGR02169  301 AEIASLERSIAEKERELEDAEERLAKLEAEIDKLLAEIEElereiEEERKRRDkLTEEYAELKEELEDLRAELEEVDKEF 380
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   448 EAAKQEL-ERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVL 526
Cdd:TIGR02169  381 AETRDELkDYREKLEKLKREINELKRELDRLQEELQRLSEELADLNAAIAGIEAKINELEEEKEDKALEIKKQEWKLEQL 460
                          170       180
                   ....*....|....*....|....*
gi 966980062   527 DKQCDLEIMEIKQLQQELQEYQNKL 551
Cdd:TIGR02169  461 AADLSKYEQELYDLKEEYDRVEKEL 485
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
988-1031 3.56e-07

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 48.55  E-value: 3.56e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE-----WWTGSIGDRSGIFPS 1031
Cdd:cd11762     4 ALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFPS 52
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
988-1036 3.81e-07

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 48.48  E-value: 3.81e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTG--SIGDRsGIFPSNYVKP 1036
Cdd:cd11763     4 ALYDFDSQPSGELSLRAGEVLTITRQDVGdgWLEGrnSRGEV-GLFPSSYVEI 55
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
1571-1663 3.87e-07

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 49.87  E-value: 3.87e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPddfLGR 1650
Cdd:cd04050     2 LFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKS---LGS 78
                          90
                  ....*....|...
gi 966980062 1651 TEIPVAKIRTEQE 1663
Cdd:cd04050    79 LTLPLSELLKEPD 91
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
902-950 3.88e-07

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 48.25  E-value: 3.88e-07
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSY 950
Cdd:cd11818     1 KARALYDFTGENEDELSFKAGDIITELESiDEEWMSGELRGKSGIFPKNF 50
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
895-953 3.91e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 48.44  E-value: 3.91e-07
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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  895 GQVVenlkaqALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11996     1 CQVI------AMYDYTANNEDELSFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVKM 54
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
988-1033 3.98e-07

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 48.53  E-value: 3.98e-07
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                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDG----EWWTGSIGDRSGIFPSNY 1033
Cdd:cd11807     5 ALFDYEAENGDELSFREGDELTVLRKGDddetEWWWARLNDKEGYVPRNL 54
SH3_Vinexin_2 cd11924
Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 ...
1131-1183 4.01e-07

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212857  Cd Length: 56  Bit Score: 48.42  E-value: 4.01e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT--GLFPSNYVKM 1183
Cdd:cd11924     2 EAVAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGTGrqGIFPASYVQV 56
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
988-1035 4.20e-07

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 48.38  E-value: 4.20e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11928     5 ALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQ 53
SH3_RIM-BP cd11851
Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding ...
1132-1182 4.65e-07

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212785  Cd Length: 62  Bit Score: 48.47  E-value: 4.65e-07
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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1132 VIAMYDY-------AANNEDELSFSKGQLINVM-NKDDPDWWQGEINGV-TGLFPSNYVK 1182
Cdd:cd11851     2 MVALYDYnpetmspNDDPEEELSFHAGDVVRVYgPMDEDGFYYGELEGGrKGLVPSNFVQ 61
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
902-953 4.71e-07

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 48.10  E-value: 4.71e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11781     1 KARALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYVEI 53
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
902-952 4.84e-07

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212713 [Multi-domain]  Cd Length: 57  Bit Score: 48.09  E-value: 4.84e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGE--VHGGRGWFPKSYVK 952
Cdd:cd11779     2 RVKALYPHAAGGETQLSFEEGDVITLLgpEPRDGWHYGEneRSGRRGWFPIAYTE 56
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
763-816 4.98e-07

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 48.08  E-value: 4.98e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd11920     4 RAVYDFKAQTSKELSFKKGDTVYILRKI--DQNWYEGEHHGRVGIFPISYVEKL 55
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
986-1038 5.24e-07

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 48.11  E-value: 5.24e-07
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTG-SIGD-RSGIFPSNYVKPKD 1038
Cdd:cd12007     3 FVALYDYEARTTEDLSFKKGERFqIINNTEGDWWEArSIATgKNGYIPSNYVAPAD 58
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
903-951 5.31e-07

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 47.87  E-value: 5.31e-07
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 951
Cdd:cd11951     2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDpNWWRGRISGRVGFFPRNYV 51
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
763-815 5.31e-07

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 48.10  E-value: 5.31e-07
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQG-NFGWFPCNYVEK 815
Cdd:cd11825     3 KALYDYRAQRPDELSFCKHAIITNVEKEDG--GWWRGDYGGkKQKWFPANYVEE 54
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
988-1035 5.34e-07

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 48.14  E-value: 5.34e-07
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVT-QKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12061     4 AKFNFQQTNEDELSFSKGDVIHVTrVEEGGWWEGTHNGRTGWFPSNYVR 52
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
987-1035 5.36e-07

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 47.76  E-value: 5.36e-07
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gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11828     3 EALWDHVTMDPEELGFKAGDVIEVLDmSDKDWWWGSIRDEEGWFPASFVR 52
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
1134-1183 5.41e-07

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212907  Cd Length: 54  Bit Score: 48.14  E-value: 5.41e-07
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11974     5 ALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54
SH3_Vinexin_3 cd11918
Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain ...
762-813 5.53e-07

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212851 [Multi-domain]  Cd Length: 58  Bit Score: 48.03  E-value: 5.53e-07
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gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN--FGWFPCNYV 813
Cdd:cd11918     4 YKAVYQYRPQNEDELELREGDRVDVMQQC--DDGWFVGVSRRTqkFGTFPGNYV 55
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
764-815 5.58e-07

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 48.10  E-value: 5.58e-07
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gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11978     5 ARYDFCARDMRELSLLKGDVVKIYTKM-STNGWWRGEVNGRVGWFPSTYVEE 55
SH3_SH3RF1_1 cd11927
First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ...
903-953 5.63e-07

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212860  Cd Length: 54  Bit Score: 48.02  E-value: 5.63e-07
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11927     3 AKALYNYEGKEPGDLKFSKGDIIILRRQvDENWYHGEVNGIHGFFPTNFVQI 54
PH_PLEKHG7 cd13245
Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; ...
1434-1540 5.73e-07

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270065  Cd Length: 128  Bit Score: 50.35  E-value: 5.73e-07
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gi 966980062 1434 KLLHSGKLYKTKSNK--ELHGFLFNDFLLLTYMVKQFAVSSGSEKLFS---------SKSNAQFKMYKTPIFLNEVLVK- 1501
Cdd:cd13245     1 QLLHEGPLTLIESGKtlDVYLFLFDDMLLITKMKKNLKKKKSSDSENSmpsleltplIKEGGSYTVYKQPIPLDRLCLHd 80
                          90       100       110       120
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gi 966980062 1502 -LPTDPSSD--EPVFHISHIDR------VYTLRTDNINERTAWVQKIK 1540
Cdd:cd13245    81 vDPNEATANglKHAFVLVHLNRyqqvigVYTLQASSENTKQTWMSKLR 128
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
986-1036 5.83e-07

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 47.98  E-value: 5.83e-07
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gi 966980062   986 YIALYPYSSVEPGDLTFTEGEEILVTQKD-GEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDnDGWWEGETGGRVGLVPSTAVEE 53
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
987-1034 6.28e-07

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 47.89  E-value: 6.28e-07
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gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGD-RSGIFPSNYV 1034
Cdd:cd11812     3 VALYDYTANRSDELTIHRGDIIRVLYKDNDnWWFGSLVNgQQGYFPANYV 52
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
902-953 6.35e-07

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 47.80  E-value: 6.35e-07
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ---QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKsdsQNDWWTGRIGGREGIFPANYVEL 55
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
986-1036 6.41e-07

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212717 [Multi-domain]  Cd Length: 55  Bit Score: 47.77  E-value: 6.41e-07
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGS--IGDRSGIFPSNYVKP 1036
Cdd:cd11783     2 YVALYPYKPQKPDELELRKGEMYTVTEKcqDG-WFKGTslRTGQSGVFPGNYVQP 55
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
1132-1181 6.44e-07

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212822  Cd Length: 53  Bit Score: 47.88  E-value: 6.44e-07
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gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEI--NGVTGLFPSNYV 1181
Cdd:cd11889     2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 53
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
988-1034 6.45e-07

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 47.90  E-value: 6.45e-07
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKD-GE--WWTGSIGDRSGIFPSNYV 1034
Cdd:cd12056     6 ALFHYEGTNEDELDFKEGEIILIISKDtGEpgWWKGELNGKEGVFPDNFV 55
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
1134-1181 6.52e-07

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 47.55  E-value: 6.52e-07
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDP--DWWQGEINGVTGLFPSNYV 1181
Cdd:cd12044     4 GLWDCFGDNPDELSFQRGDLIYILSKEYNmyGWWVGELNGIVGIVPKDYL 53
SH3_Sorbs2_3 cd11917
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), ...
762-816 7.03e-07

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212850 [Multi-domain]  Cd Length: 61  Bit Score: 48.07  E-value: 7.03e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN--FGWFPCNYVEKM 816
Cdd:cd11917     7 FQALYNYMPRNEDELELREGDVIDVMEKC--DDGWFVGTSRRTkfFGTFPGNYVKRL 61
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
1131-1182 7.12e-07

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 47.70  E-value: 7.12e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMN-KDDPDWWQGEI--NGVTGLFPSNYVK 1182
Cdd:cd11775     2 RGKVLYDFDAQSDDELTVKEGDVVYILDdKKSKDWWMVENvsTGKEGVVPASYIE 56
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
763-813 7.25e-07

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 47.64  E-value: 7.25e-07
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                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11964     4 RAIYDFEAAEDNELTFKAGDIITILDDS--DPNWWKGETPQGTGLFPSNFV 52
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
763-816 7.52e-07

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 47.65  E-value: 7.52e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd12054     4 KVLFEYVPQNEDELELKVGDIIDINEEV--EEGWWSGTLNGKSGLFPSNFVKEL 55
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
917-951 7.63e-07

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 47.51  E-value: 7.63e-07
                          10        20        30
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gi 966980062  917 LNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 951
Cdd:cd11829    17 LSFEAGELIRVLQAPDGgWWEGEKDGLRGWFPASYV 52
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
985-1035 7.64e-07

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 47.34  E-value: 7.64e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11782     1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYVQ 52
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
903-953 7.66e-07

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 47.69  E-value: 7.66e-07
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                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGG-RGWFPKSYVKI 953
Cdd:cd11819     2 AKALYDYQAAEDNEISFVEGDIITQIEQiDEGWWLGVNAKGqKGLFPANYVEL 54
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
1057-1112 7.72e-07

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 47.65  E-value: 7.72e-07
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gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHV 1112
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNG-----QVGWFPSNYV 51
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
764-812 7.74e-07

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212712 [Multi-domain]  Cd Length: 51  Bit Score: 47.49  E-value: 7.74e-07
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gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGWLYGSFQGNFGWFPCNY 812
Cdd:cd11778     4 ALYDYEAQGDDEISIRVGDRIAVIRGDDGS-GWTYGEINGVKGLFPTSY 51
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
763-814 7.88e-07

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 47.53  E-value: 7.88e-07
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                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11949     3 QALFDFDPQEDGELGFRRGDFIEVMDNS--DPNWWKGACHGQTGMFPRNYVT 52
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
985-1036 8.12e-07

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 47.31  E-value: 8.12e-07
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gi 966980062  985 EYIALYPYSSVEPGDLTFTEGE--EILVTQKDGeWWTG--SIGDRsGIFPSNYVKP 1036
Cdd:cd11770     1 LYEALSDFQAEQEGDLSFKKGEvlRIISKRADG-WWLAenSKGNR-GLVPKTYLKV 54
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
985-1035 8.16e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 47.64  E-value: 8.16e-07
                          10        20        30        40        50
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gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11995     2 QVIGMYDYTAQNDDELAFSKGQIInVLNKEDPDWWKGELNGQVGLFPSNYVK 53
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
762-814 8.26e-07

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 47.32  E-value: 8.26e-07
                          10        20        30        40        50
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gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGWLYG-SFQGNFGWFPCNYVE 814
Cdd:cd11763     2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGD-GWLEGrNSRGEVGLFPSSYVE 54
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
987-1036 8.35e-07

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 47.27  E-value: 8.35e-07
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                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGD-RSGIFPSNYVKP 1036
Cdd:cd11768     3 VALYDFQPIEPGDLPLEKGEEYVVLDDSNEhWWRARDKNgNEGYIPSNYVTE 54
SH3_PACSIN_like cd11999
Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C ...
1131-1181 8.43e-07

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212932 [Multi-domain]  Cd Length: 56  Bit Score: 47.63  E-value: 8.43e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQ-LINVMNKDDPDWWQGEIN-GVTGLFPSNYV 1181
Cdd:cd11999     3 RVRAVYDYTGQEPDELSFKAGEeLLKVEDEDEQGWCKGVTDgGAVGLYPANYV 55
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
764-814 8.93e-07

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 47.52  E-value: 8.93e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  764 ALYPFEARNHDEMSFNSGDII----QVDEktigepGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12073     5 ALYDYQGEGDDEISFDPQETItdieMVDE------GWWKGTCHGHRGLFPANYVE 53
SH3_GRAF3 cd12066
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is ...
1131-1181 9.45e-07

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212999  Cd Length: 55  Bit Score: 47.36  E-value: 9.45e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLI-NVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd12066     1 QAKAMYSCKAEHSHELSFPQGAIFsNVYPSVEPGWLKATYEGKTGLVPENYV 52
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
988-1034 9.55e-07

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 47.25  E-value: 9.55e-07
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11964     5 AIYDFEAAEDNELTFKAGDIItILDDSDPNWWKGETPQGTGLFPSNFV 52
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
986-1036 9.59e-07

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 47.24  E-value: 9.59e-07
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGE------WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd12058     2 WTALYDYEASGEDELSLRRGDVVEVLSQDAAvsgddgWWAGKIRHRLGIFPANYVTR 58
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
764-814 9.65e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 47.28  E-value: 9.65e-07
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gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11996     5 AMYDYTANNEDELSFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 53
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
988-1034 9.74e-07

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 47.26  E-value: 9.74e-07
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVT-QKDGEWWTGSI-GD--RSGIFPSNYV 1034
Cdd:cd11966     4 ALYNCVADNPDELTFSEGEIIIVDgEEDKEWWIGHIdGEptRRGAFPVSFV 54
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
988-1035 1.01e-06

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212862  Cd Length: 54  Bit Score: 47.24  E-value: 1.01e-06
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILV-TQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11929     5 ALCNYRGHNPGDLKFNKGDVILLrRQLDENWYLGEINGVSGIFPASSVE 53
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
1058-1112 1.01e-06

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 47.31  E-value: 1.01e-06
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gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHV 1112
Cdd:cd11902     3 AFVKFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNG-----QIGWFPSNYV 52
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
1058-1115 1.04e-06

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 47.21  E-value: 1.04e-06
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gi 966980062  1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELqargkKRQKGWFPASHVKLL 1115
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGET-----GGRVGLVPSTAVEEI 54
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
761-815 1.05e-06

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 47.02  E-value: 1.05e-06
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gi 966980062  761 NYRALYPFEARNHDEMSFNSGDIIQVDEKTiGEpgWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11838     1 EYIALYPYESNEPGDLTFNAGDVILVTKKD-GE--WWTGTIGDRTGIFPSNYVRP 52
SH3_GRAF cd12064
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also ...
1134-1182 1.06e-06

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212997  Cd Length: 56  Bit Score: 47.42  E-value: 1.06e-06
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLI-NVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12064     5 ALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVE 54
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
988-1035 1.10e-06

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 47.30  E-value: 1.10e-06
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12060     6 ARFNFKQTNEDELSVCKGDIIYVTRvEEGGWWEGTLNGKTGWFPSNYVR 54
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
903-952 1.15e-06

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212775  Cd Length: 54  Bit Score: 47.00  E-value: 1.15e-06
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVL---EQQENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11841     2 VTALYSFEGQQPCDLSFQAGDRITVLtrtDSQFDWWEGRLRGRVGIFPANYVS 54
SH3_UBASH3 cd11791
Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called ...
762-815 1.17e-06

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212725 [Multi-domain]  Cd Length: 59  Bit Score: 47.30  E-value: 1.17e-06
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gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEP--GWLYGSFQ--GNFGWFPCNYVEK 815
Cdd:cd11791     2 LRVLYPYTPQEEDELELVPGDYIYVSPEELDSSsdGWVEGTSWltGCSGLLPENYTEK 59
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
763-812 1.17e-06

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 46.71  E-value: 1.17e-06
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gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNY 812
Cdd:cd11818     3 RALYDFTGENEDELSFKAGDIIteleSIDEE------WMSGELRGKSGIFPKNF 50
SH3_SH3RF2_3 cd11784
Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
1133-1181 1.23e-06

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212718  Cd Length: 55  Bit Score: 47.08  E-value: 1.23e-06
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd11784     3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLslVTGRVGIFPSNYV 53
SH3_Brk cd11847
Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called ...
986-1034 1.24e-06

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212781 [Multi-domain]  Cd Length: 58  Bit Score: 47.17  E-value: 1.24e-06
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDRS------GIFPSNYV 1034
Cdd:cd11847     2 YKALWDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRAggvvaqGFVPNNYL 56
SH3_Sorbs2_3 cd11917
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), ...
1134-1182 1.24e-06

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212850 [Multi-domain]  Cd Length: 61  Bit Score: 47.29  E-value: 1.24e-06
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT--GLFPSNYVK 1182
Cdd:cd11917     9 ALYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTKffGTFPGNYVK 59
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
902-953 1.28e-06

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 46.99  E-value: 1.28e-06
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11828     1 LAEALWDHVTMDPEELGFKAGDVIEVLDMSDkDWWWGSIRDEEGWFPASFVRL 53
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
1134-1181 1.32e-06

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 46.74  E-value: 1.32e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1134 AMYDYAANNEDE-LSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11829     4 TLYAFTGEQHQQgLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
335-756 1.42e-06

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 53.14  E-value: 1.42e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  335 KQIDSINGTLPSYQKIQEEEPQKKlpvtfedKRKANYERGNMELEKRRQAlVEQQQREAERKaQKEKEEWERKQRELQeq 414
Cdd:PRK03918  283 KELKELKEKAEEYIKLSEFYEEYL-------DELREIEKRLSRLEEEING-IEERIKELEEK-EERLEELKKKLKELE-- 351
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  415 ewKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQrrLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLE 494
Cdd:PRK03918  352 --KRLEELEERHELYEEAKAKKEELERLKKRLTGLTPEKLEKE--LEELEKAKEEIEEEISKITARIGELKKEIKELKKA 427
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  495 LEALNGKHQQ--ISGRLQDVRLKKQTQKT---ELEVLDKqcdlEIMEIKQLQQELQEYQNKL-IYLVPEKQLLNERIKNM 568
Cdd:PRK03918  428 IEELKKAKGKcpVCGRELTEEHRKELLEEytaELKRIEK----ELKEIEEKERKLRKELRELeKVLKKESELIKLKELAE 503
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  569 QFSNTPDSGVSLLHKKSLEKQELCQRLKEQLDALEKET---ASKLSEMDSYNNQLKCGN--MDDSVLQCLLSLLSCLNNL 643
Cdd:PRK03918  504 QLKELEEKLKKYNLEELEKKAEEYEKLKEKLIKLKGEIkslKKELEKLEELKKKLAELEkkLDELEEELAELLKELEELG 583
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  644 FLLLKELRETCNTqqlaLEQLYK--IK-RDKLKEIERKrLELIQKKKLEDEAARKAKQGKENLWKEnLRREEEEKQKRLQ 720
Cdd:PRK03918  584 FESVEELEERLKE----LEPFYNeyLElKDAEKELERE-EKELKKLEEELDKAFEELAETEKRLEE-LRKELEELEKKYS 657
                         410       420       430
                  ....*....|....*....|....*....|....*.
gi 966980062  721 EEKTQEKIQEEERKAEEKQRKDKDtLKVEEKQRETA 756
Cdd:PRK03918  658 EEEYEELREEYLELSRELAGLRAE-LEELEKRREEI 692
SH3_SH3RF_2 cd11787
Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
1131-1180 1.46e-06

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212721 [Multi-domain]  Cd Length: 53  Bit Score: 46.56  E-value: 1.46e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1131 QVIAMYDYAANNEDE---LSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11787     1 QCKALYDFEMKDEDEkdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53
SH3_FCHSD1_2 cd11895
Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain ...
1134-1182 1.54e-06

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212828  Cd Length: 58  Bit Score: 46.88  E-value: 1.54e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD----DPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11895     4 ALYSYTGQSPEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 56
SH3_EFS cd12003
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
1134-1183 1.57e-06

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212936  Cd Length: 62  Bit Score: 46.81  E-value: 1.57e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPD---WWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12003     5 ALYDNAAESPEELSFRRGDVLMVLKREHGSlpgWWLCSLHGQQGIAPANRLRL 57
SH3_RIM-BP_3 cd12013
Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs ...
1131-1182 1.61e-06

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212946  Cd Length: 61  Bit Score: 46.99  E-value: 1.61e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1131 QVIAMYDYAAN----NED---ELSFSKGQLINVMNKDDPD-WWQGEINGVTGLFPSNYVK 1182
Cdd:cd12013     1 RMVALFDYDPResspNVDaevELSFRAGDIITVFGEMDEDgFYYGELNGQRGLVPSNFLE 60
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
988-1035 1.67e-06

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 46.76  E-value: 1.67e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDR-SGIFPSNYVK 1035
Cdd:cd11969     4 ALYDYRAKRSDELSFCKGALIHnVSKETGGWWKGDYGGKvQHYFPSNYVE 53
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
376-741 1.69e-06

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 52.23  E-value: 1.69e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   376 MELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLElEKRLEKQRELERQREEerrkeierreaAKQELE 455
Cdd:pfam13868   38 EKEEERRLDEMMEEERERALEEEEEKEEERKEERKRYRQELEEQIE-EREQKRQEEYEEKLQE-----------REQMDE 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   456 RQRRLEWERIRRQELLNQKNR----EQEEIVRLNSKKKSLHLELEalngkhqqisgRLQDVRLKK-QTQKTELEVLDKQc 530
Cdd:pfam13868  106 IVERIQEEDQAEAEEKLEKQRqlreEIDEFNEEQAEWKELEKEEE-----------REEDERILEyLKEKAEREEEREA- 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   531 dlEIMEIKQlqqelqeyqnkliylvpEKQLLNERIknmqfsntpdsgvsllhkksLEKQELCQRLKEQLDAL-------E 603
Cdd:pfam13868  174 --EREEIEE-----------------EKEREIARL--------------------RAQQEKAQDEKAERDELraklyqeE 214
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   604 KETASKLSEMDSYNNQLKcgnMDDSVLQcllsllsclnnLFLLLKELRETCNTQQLALEQLYKIK-RDKLKEIERKRLEL 682
Cdd:pfam13868  215 QERKERQKEREEAEKKAR---QRQELQQ-----------AREEQIELKERRLAEEAEREEEEFERmLRKQAEDEEIEQEE 280
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 966980062   683 IQKKKledEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERK--AEEKQRK 741
Cdd:pfam13868  281 AEKRR---MKRLEHRRELEKQIEEREEQRAAEREEELEEGERLREEEAERREriEEERQKK 338
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
902-951 1.71e-06

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 46.69  E-value: 1.71e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ---ENWWFGEVHGGRGWFPKSYV 951
Cdd:cd12142     1 YCRVLFDYNPVAPDELALKKGDVIEVISKEtedEGWWEGELNGRRGFFPDNFV 53
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
1132-1183 1.71e-06

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 46.54  E-value: 1.71e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE-INGVTGLFPSNYVKM 1183
Cdd:cd11770     2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAEnSKGNRGLVPKTYLKV 54
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
902-951 1.75e-06

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 46.55  E-value: 1.75e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 951
Cdd:cd11826     1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51
SH3_MPP7 cd12033
Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); ...
1132-1180 1.75e-06

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212966  Cd Length: 61  Bit Score: 46.94  E-value: 1.75e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1132 VIAMYDYAAN-------NEDELSFSKGQLINVMNKDDPDWWQ----GEINGVTGLFPSNY 1180
Cdd:cd12033     2 IKALFDYNPNedkaipcKEAGLSFKKGDILQIMSQDDATWWQakheGDANPRAGLIPSKH 61
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
988-1035 1.78e-06

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 46.56  E-value: 1.78e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGE--EILVTQKDGeWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11874     4 VLFSYTPQNEDELELKVGDtiEVLGEVEEG-WWEGKLNGKVGVFPSNFVK 52
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
763-815 1.85e-06

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 46.56  E-value: 1.85e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN-----FGWFPCNYVEK 815
Cdd:cd11839     3 QVIAPFTATAENQLSLAVGQLVLVRKKS--PSGWWEGELQARgkkrqIGWFPANYVKL 58
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
763-813 1.86e-06

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 46.35  E-value: 1.86e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDE-MSFNSGDIIQVDEktIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11829     3 RTLYAFTGEQHQQgLSFEAGELIRVLQ--APDGGWWEGEKDGLRGWFPASYV 52
SH3_SH3RF2_3 cd11784
Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
986-1036 1.96e-06

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212718  Cd Length: 55  Bit Score: 46.31  E-value: 1.96e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGEWW-------TGsigdRSGIFPSNYVKP 1036
Cdd:cd11784     2 CVALHSYSAHRPEELELQKGEGVRVLGKFQEGWlrglslvTG----RVGIFPSNYVSP 55
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
763-814 1.96e-06

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 46.45  E-value: 1.96e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11928     4 KALYSYEGKEPGDLKFNKGDIIILRRKV--DENWYHGELNGCHGFLPASYIQ 53
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
762-815 2.08e-06

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 46.11  E-value: 2.08e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDIITNVKKM--EEGWWEGTLNGKRGMFPDNFVKV 53
SH3_Intersectin1_2 cd11989
Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
763-814 2.10e-06

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212922 [Multi-domain]  Cd Length: 52  Bit Score: 46.25  E-value: 2.10e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKtigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11989     3 QALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 51
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
914-952 2.13e-06

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 46.22  E-value: 2.13e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 966980062  914 DNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 952
Cdd:cd12061    13 EDELSFSKGDVIHVTRVEEGgWWEGTHNGRTGWFPSNYVR 52
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
763-816 2.14e-06

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 46.52  E-value: 2.14e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFG-WFPCNYVEKM 816
Cdd:cd11970     7 KALFDYKAQREDELTFTKNAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVEEI 59
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
988-1035 2.18e-06

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 46.17  E-value: 2.18e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDR-SGIFPSNYVK 1035
Cdd:cd11825     4 ALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKkQKWFPANYVE 53
SH3_Vinexin_3 cd11918
Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain ...
1134-1181 2.18e-06

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212851 [Multi-domain]  Cd Length: 58  Bit Score: 46.49  E-value: 2.18e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG--EINGVTGLFPSNYV 1181
Cdd:cd11918     6 AVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGvsRRTQKFGTFPGNYV 55
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
764-814 2.20e-06

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 46.10  E-value: 2.20e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11995     5 GMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGELNGQVGLFPSNYVK 53
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
1064-1114 2.20e-06

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 46.22  E-value: 2.20e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVKL 1114
Cdd:cd11828     8 HVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDE-----EGWFPASFVRL 53
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
377-741 2.23e-06

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 52.46  E-value: 2.23e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  377 ELEKRRQALVEQQQREAE-RKAQKEKEEWERKQRELQEQEWKKQLELEkRLEKQRELERQREEERrkeierreAAKQEL- 454
Cdd:COG4717    72 ELKELEEELKEAEEKEEEyAELQEELEELEEELEELEAELEELREELE-KLEKLLQLLPLYQELE--------ALEAELa 142
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  455 ---ERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKH-QQISGRLQDVRLKKQTQKTELEVLDKqc 530
Cdd:COG4717   143 elpERLEELEERLEELRELEEELEELEAELAELQEELEELLEQLSLATEEElQDLAEELEELQQRLAELEEELEEAQE-- 220
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  531 dleimEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFsntpdSGVSLLHKKSLEKQELCQRLKEQLDA--------- 601
Cdd:COG4717   221 -----ELEELEEELEQLENELEAAALEERLKEARLLLLIA-----AALLALLGLGGSLLSLILTIAGVLFLvlgllallf 290
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  602 --LEKETASKLSEMDSYNNQLKCGNMDD-SVLQCLLSLLSCLNNLFLLLKELRETCNTQQLALEQLYKIKRD-KLKEIER 677
Cdd:COG4717   291 llLAREKASLGKEAEELQALPALEELEEeELEELLAALGLPPDLSPEELLELLDRIEELQELLREAEELEEElQLEELEQ 370
                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  678 KRLELIQKKKLEDEAA----------RKAKQGKENLWKENLRR---EEEEKQKRLQEEKTQEKIQEEERKAEEKQRK 741
Cdd:COG4717   371 EIAALLAEAGVEDEEElraaleqaeeYQELKEELEELEEQLEEllgELEELLEALDEEELEEELEELEEELEELEEE 447
SH3_NoxO1_2 cd12024
Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox ...
1134-1182 2.25e-06

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212957  Cd Length: 53  Bit Score: 46.18  E-value: 2.25e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12024     4 ATRAYEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQ 52
ARGLU pfam15346
Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is ...
348-488 2.26e-06

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.


Pssm-ID: 405931 [Multi-domain]  Cd Length: 151  Bit Score: 49.28  E-value: 2.26e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   348 QKIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRQAlveQQQREAERKAQKEKEEWERKQRE----LQEQEWKKQLELE 423
Cdd:pfam15346   22 KRVEEELEKRKDEIEAEVERRVEEARKIMEKQVLEEL---EREREAELEEERRKEEEERKKREelerILEENNRKIEEAQ 98
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966980062   424 KRLEKQRELerqreeerrkeierreaakqELERQRRLEWERIRRQELLNQKNREQEEIVrLNSKK 488
Cdd:pfam15346   99 RKEAEERLA--------------------MLEEQRRMKEERQRREKEEEEREKREQQKI-LNKKN 142
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
762-815 2.26e-06

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 46.21  E-value: 2.26e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11824     2 YSVLYDYTAQEDDELSISKGDVVAVIEK--GEDGWWTVERNGQKGLVPGTYLEK 53
SH3_Noxa1_C cd12047
C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox ...
987-1036 2.31e-06

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212980  Cd Length: 53  Bit Score: 46.35  E-value: 2.31e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd12047     3 VAQHDYSAQGPEDLEFSQGDTIdILSEVNQEWLEGHCDGRIGIFPKCFAVR 53
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
905-952 2.31e-06

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 46.09  E-value: 2.31e-06
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gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 952
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDSgWWYVRKGDKEGWVPASYLE 52
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1064-1114 2.36e-06

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 46.13  E-value: 2.36e-06
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gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHVKL 1114
Cdd:cd11996     9 YTANNEDELSFSKGQLINVLNKDDPDWWQGEING-----VTGLFPSNYVKM 54
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
763-814 2.49e-06

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 46.15  E-value: 2.49e-06
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYG-SFQGNFGWFPCNYVE 814
Cdd:cd11767     3 VALYPFTGENDEELSFEKGERLEIIEKPEDDPDWWKArNALGTTGLVPRNYVE 55
SH3_Sorbs1_1 cd11919
First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; ...
1131-1183 2.89e-06

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212852 [Multi-domain]  Cd Length: 55  Bit Score: 46.11  E-value: 2.89e-06
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11919     2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1134-1182 2.91e-06

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212921 [Multi-domain]  Cd Length: 57  Bit Score: 46.02  E-value: 2.91e-06
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11988     6 ALYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
1063-1112 2.91e-06

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 45.87  E-value: 2.91e-06
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gi 966980062 1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELqaRGKkrqKGWFPASHV 1112
Cdd:cd11827     7 AYDAQDTDELSFNEGDIIEILKEDPSGWWTGRL--RGK---EGLFPGNYV 51
SH3_MPP1 cd12080
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); ...
1136-1178 3.02e-06

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213013  Cd Length: 62  Bit Score: 46.10  E-value: 3.02e-06
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gi 966980062 1136 YDYAANN-----EDELSFSKGQLINVMNKDDPDWWQGEINGV----TGLFPS 1178
Cdd:cd12080     8 YDPKKDNlipckEAGLKFQTGDIIQIINKDDSNWWQGRVEGSgeesAGLIPS 59
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
985-1035 3.21e-06

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 45.66  E-value: 3.21e-06
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gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12052     1 EAIVEFDYKAQHEDELTITVGDIITkIKKDDGGWWEGEIKGRRGLFPDNFVR 52
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
903-953 3.27e-06

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 45.87  E-value: 3.27e-06
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11959     2 AVALYDYQAADDDEISFDPDDIITNIEMiDEGWWRGVCRGKYGLFPANYVEL 53
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
764-813 3.38e-06

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212775  Cd Length: 54  Bit Score: 45.85  E-value: 3.38e-06
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gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11841     4 ALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANYV 53
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
903-952 3.41e-06

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 45.71  E-value: 3.41e-06
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ--QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11976     2 AKARYDFCARDRSELSLKEGDIIKILNKkgQQGWWRGEIYGRVGWFPANYVE 53
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
1132-1181 3.41e-06

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212839 [Multi-domain]  Cd Length: 55  Bit Score: 45.59  E-value: 3.41e-06
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gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG-EINGVTGLFPSNYV 1181
Cdd:cd11906     3 VVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRArDKNGREGYIPSNYV 53
SH3_SH3BP4 cd11757
Src Homology 3 domain of SH3 domain-binding protein 4; SH3 domain-binding protein 4 (SH3BP4) ...
1131-1182 3.45e-06

Src Homology 3 domain of SH3 domain-binding protein 4; SH3 domain-binding protein 4 (SH3BP4) is also called transferrin receptor trafficking protein (TTP). SH3BP4 is an endocytic accessory protein that interacts with endocytic proteins including clathrin and dynamin, and regulates the internalization of the transferrin receptor (TfR). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212691  Cd Length: 52  Bit Score: 45.78  E-value: 3.45e-06
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11757     1 EVVAIKDYCPTNFTTLKFSKGDHLYVLDTSGGEWWYAHNTTEMGYIPSSYVQ 52
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
905-953 3.55e-06

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212805 [Multi-domain]  Cd Length: 56  Bit Score: 45.65  E-value: 3.55e-06
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gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEV---HGGRGWFPKSYVKI 953
Cdd:cd11872     4 AIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGFSlrnKSLKGIFPKSYVHI 55
SH3_Bzz1_1 cd11912
First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
1134-1183 3.57e-06

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212845 [Multi-domain]  Cd Length: 55  Bit Score: 45.68  E-value: 3.57e-06
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQgEI---NGVTGLFPSNYVKM 1183
Cdd:cd11912     4 VLYDYTASGDDEVSISEGEEVTVLEPDDGSGWT-KVrngSGEEGLVPTSYIEI 55
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
1569-1663 3.66e-06

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 47.96  E-value: 3.66e-06
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gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISM---GSQSYT--TRTIQDTLNPKWnfNCQFFIK----DLYQDVLCLTLFDR 1639
Cdd:cd00276    14 ERLTVVVLKARNLPPSDGKGLSDPYVKVSLlqgGKKLKKkkTSVKKGTLNPVF--NEAFSFDvpaeQLEEVSLVITVVDK 91
                          90       100
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gi 966980062 1640 DQFSPDDFLGRTEIPVAKIRTEQE 1663
Cdd:cd00276    92 DSVGRNEVIGQVVLGPDSGGEELE 115
SH3_Intersectin1_2 cd11989
Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1131-1183 3.83e-06

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212922 [Multi-domain]  Cd Length: 52  Bit Score: 45.48  E-value: 3.83e-06
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPdWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11989     1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 52
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
903-953 3.89e-06

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 45.59  E-value: 3.89e-06
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd12073     3 AVALYDYQGEGDDEISFDPQETITDIEMvDEGWWKGTCHGHRGLFPANYVEL 54
SH3_Intersectin1_1 cd11987
First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1134-1182 4.09e-06

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212920 [Multi-domain]  Cd Length: 55  Bit Score: 45.38  E-value: 4.09e-06
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11987     4 ALYPFEARSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 54
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
902-953 4.19e-06

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 45.44  E-value: 4.19e-06
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11824     1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYLEK 53
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
763-814 4.20e-06

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 45.59  E-value: 4.20e-06
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gi 966980062  763 RALYPFEARNHDEMSFNSGD-IIQVDektIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11961     3 KALYDYDAAEDNELSFFENDkIINIE---FVDDDWWLGECHGSRGLFPSNYVE 52
SH3_Shank1 cd11982
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also ...
1133-1181 4.27e-06

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212915 [Multi-domain]  Cd Length: 52  Bit Score: 45.39  E-value: 4.27e-06
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11982     4 MAVKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
1132-1182 4.30e-06

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212717 [Multi-domain]  Cd Length: 55  Bit Score: 45.46  E-value: 4.30e-06
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gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGE--INGVTGLFPSNYVK 1182
Cdd:cd11783     2 YVALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTslRTGQSGVFPGNYVQ 54
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
1433-1554 4.32e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 47.65  E-value: 4.32e-06
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gi 966980062 1433 RKLLHSGKLYKTkSNKEL---HGFLFNDFLLLTYMVKqfavssgseklfsskSNAQFKMYKTPIFLNeVLVKLPTDPS-S 1508
Cdd:cd13389    12 RKLIKEGELMKV-SRKEMqprYFFLFNDCLLYTTPVQ---------------SSGMLKLNNELPLSG-MKVKLPEDEEyS 74
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gi 966980062 1509 DEpvFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYidteKKKR 1554
Cdd:cd13389    75 NE--FQIISTKRSFTLIASSEEERDEWVKALSRAIEEH----TKKQ 114
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1134-1183 4.35e-06

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 45.42  E-value: 4.35e-06
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDpDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11990     4 ALCSWTAKKDNHLNFSKNDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKL 52
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
903-953 4.46e-06

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212907  Cd Length: 54  Bit Score: 45.44  E-value: 4.46e-06
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11974     3 AEALWDHVTMDDQELAFKAGDVIRVLEaSNKDWWWGRNEDREAWFPASFVRL 54
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
763-813 4.57e-06

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212837 [Multi-domain]  Cd Length: 57  Bit Score: 45.40  E-value: 4.57e-06
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLY-GSFQGNFGWFPCNYV 813
Cdd:cd11904     4 QALYPFSSSNDEELNFEKGEVMDVIEKPENDPEWWKcRKANGQVGLVPKNYV 55
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
763-815 4.69e-06

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212820 [Multi-domain]  Cd Length: 60  Bit Score: 45.41  E-value: 4.69e-06
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNF-----GWFPCNYVEK 815
Cdd:cd11887     5 KALYPYESDHEDDLNFDVGQLITVTEEEDAD--WYFGEYVDSNgntkeGIFPKNFVEV 60
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
763-814 4.75e-06

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 45.40  E-value: 4.75e-06
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11874     3 KVLFSYTPQNEDELELKVGDTIEVLGEV--EEGWWEGKLNGKVGVFPSNFVK 52
SH3_Stac2_C cd11985
C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); ...
1133-1182 5.10e-06

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212918  Cd Length: 53  Bit Score: 45.32  E-value: 5.10e-06
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd11985     3 VALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
903-952 5.24e-06

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 45.20  E-value: 5.24e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11950     2 VRALYDFEALEDDELGFNSGDVIEVLDSSNpSWWKGRLHGKLGLFPANYVA 52
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
1058-1112 5.42e-06

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 45.03  E-value: 5.42e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHV 1112
Cdd:cd11901     4 AYVKFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQ-----VGWFPSNYV 53
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
989-1036 5.44e-06

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 45.15  E-value: 5.44e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  989 LYPYSSVEPGDLTFTEGEEILVTQKDGE---WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd12142     5 LFDYNPVAPDELALKKGDVIEVISKETEdegWWEGELNGRRGFFPDNFVMP 55
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
763-814 5.52e-06

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212798  Cd Length: 58  Bit Score: 45.31  E-value: 5.52e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGE--PGWLYGSFQG-NFGWFPCNYVE 814
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDKLRLAPKELQPrvRGWLLATVDGqKIGLVPANYVK 57
SH3_GRAP2_N cd11947
N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
902-953 5.64e-06

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212880 [Multi-domain]  Cd Length: 52  Bit Score: 45.17  E-value: 5.64e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11947     1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFVDI 52
SH3_DNMBP_C2 cd12141
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
1134-1182 5.77e-06

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213017 [Multi-domain]  Cd Length: 57  Bit Score: 45.18  E-value: 5.77e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDD----PDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12141     4 AVYTFKARSPNELSVSANQRVRILEFSDltgnKEWWLAEANGQKGYVPSNYIR 56
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
1589-1680 6.54e-06

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 46.79  E-value: 6.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1589 KSNPYCEISM---GSQSYT----TRTIQDTLNPkwNFNCQFFIKDLYQDV--LCLTLFDRDQFSPD----DFLGRTEIPV 1655
Cdd:cd04048    20 KSDPFVVVYVktgGSGQWVeigrTEVIKNNLNP--DFVTTFTVDYYFEEVqkLRFEVYDVDSKSKDlsdhDFLGEAECTL 97
                          90       100
                  ....*....|....*....|....*
gi 966980062 1656 AKIrteQESKGPVTRRLLLHEVPTG 1680
Cdd:cd04048    98 GEI---VSSPGQKLTLPLKGGKGKG 119
SH3_Sorbs1_2 cd11922
Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ...
1131-1183 6.72e-06

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212855 [Multi-domain]  Cd Length: 58  Bit Score: 44.98  E-value: 6.72e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT--GLFPSNYVKM 1183
Cdd:cd11922     2 EAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGTSrqGIFPITYVDV 56
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
988-1035 6.89e-06

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 44.70  E-value: 6.89e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGD-RSGIFPSNYVK 1035
Cdd:cd11960     4 ALYDYQAADDTEISFDPGDIITdIEQIDEGWWRGTGPDgTYGLFPANYVE 53
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
763-813 7.00e-06

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 44.71  E-value: 7.00e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKtIGEPgWLYGSFQGNFGWFPCNYV 813
Cdd:cd11816     3 VARFDFEGEQEDELSFSEGDVITLKEY-VGEE-WAKGELNGKIGIFPLNFV 51
SH3_Tks5_2 cd12077
Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
762-815 7.38e-06

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213010  Cd Length: 54  Bit Score: 44.64  E-value: 7.38e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIgePGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12077     3 YVTVQPYTSQGKDEIGFEKGVTVEVIQKNL--EGWWYIRYLGKEGWAPASYLKK 54
Mplasa_alph_rch TIGR04523
helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...
387-738 7.49e-06

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.


Pssm-ID: 275316 [Multi-domain]  Cd Length: 745  Bit Score: 50.79  E-value: 7.49e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   387 EQQQREAERKAQKEKEEWERKQRELQEQEWKKQlELEKRLEKQRELERQREEERrkeierreaakQELERQRRLEWERIr 466
Cdd:TIGR04523  362 QRELEEKQNEIEKLKKENQSYKQEIKNLESQIN-DLESKIQNQEKLNQQKDEQI-----------KKLQQEKELLEKEI- 428
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   467 rQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQE 546
Cdd:TIGR04523  429 -ERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRESLETQLKVLSRSINKIKQNLEQKQKELKSKEKELKKLNEEKKE 507
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   547 YQNKLIYLVPEKQLLNERIKNMqfsntpdsgvsllhkkSLEKQElcqrlkeqldaLEKETASKLSEMDSYNNQLKCGNMD 626
Cdd:TIGR04523  508 LEEKVKDLTKKISSLKEKIEKL----------------ESEKKE-----------KESKISDLEDELNKDDFELKKENLE 560
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   627 DSVLQCLLSLLSCLNNLFLLLKELREtcntqqlaLEQLYKIKRDKLKEIERKRLELIQKK-KLEDEaARKAKqgKENLWK 705
Cdd:TIGR04523  561 KEIDEKNKEIEELKQTQKSLKKKQEE--------KQELIDQKEKEKKDLIKEIEEKEKKIsSLEKE-LEKAK--KENEKL 629
                          330       340       350
                   ....*....|....*....|....*....|...
gi 966980062   706 ENLRREEEEKQKRLQEEKTQekIQEEERKAEEK 738
Cdd:TIGR04523  630 SSIIKNIKSKKNKLKQEVKQ--IKETIKEIRNK 660
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
1134-1182 7.50e-06

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 44.68  E-value: 7.50e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT--GLFPSNYVK 1182
Cdd:cd11858     4 ALYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESkeGWVPAAYLE 54
SH3_BAIAP2L2 cd11914
Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; ...
772-816 7.57e-06

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212847 [Multi-domain]  Cd Length: 59  Bit Score: 44.81  E-value: 7.57e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  772 NHDEMSFNSGDIIQVdekTIGEP--GWLYGSFQGNF--GWFPCNYVEKM 816
Cdd:cd11914    14 NPTLLRFNRGDIITV---LVPEArnGWLYGKLEGSSrqGWFPEAYVKAL 59
SH3_ARHGEF9 cd11975
Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also ...
1134-1183 7.66e-06

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212908  Cd Length: 62  Bit Score: 45.09  E-value: 7.66e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11975     9 AVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
762-815 7.82e-06

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 44.67  E-value: 7.82e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEK--TIGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11800     2 YYALYTFEARSPGELSVTEGQVVTVLEKhdLKGNPEWWLVEDRGKQGYVPSNYLAK 57
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
988-1034 8.24e-06

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 44.72  E-value: 8.24e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPY--SSVEPGDLTFTEGEEILVTQKDGEWWTGSIGD-RSGIFPSNYV 1034
Cdd:cd11855     4 ALYPYdaSPDDPNELSFEKGEILEVSDTSGKWWQARKSNgETGICPSNYL 53
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
909-953 8.37e-06

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 44.56  E-value: 8.37e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062  909 WTAKKDNHLNFSKHDIIT-VLEQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11873     8 YDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVKV 53
SH3_GRAF2 cd12065
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also ...
1134-1183 8.49e-06

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212998 [Multi-domain]  Cd Length: 54  Bit Score: 44.59  E-value: 8.49e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1134 AMYDYAANNEDELSFSKGQLI-NVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12065     4 AVYPCEAEHSSELSFEVGAIFeDVTLSREPGWLEGTLNGKRGLIPENYVEI 54
SH3_MPP1-like cd12035
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1) ...
1132-1178 8.63e-06

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212968  Cd Length: 62  Bit Score: 44.73  E-value: 8.63e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1132 VIAMYDYAANNED-------ELSFSKGQLINVMNKDDPDWWQ----GEINGVTGLFPS 1178
Cdd:cd12035     2 VRAQFDYDPSKDDlipcqqaGIAFKTGDILQIISKDDHNWWQarkpGASKEPAGLIPS 59
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
366-765 8.72e-06

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 50.83  E-value: 8.72e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  366 KRKANYERGNMELEKRRQAL--VEQQQREAER-KAQKEKEEWERKQRELQEQEwKKQLELEKRLEKqrelERQREEERRK 442
Cdd:PRK03918  345 KKLKELEKRLEELEERHELYeeAKAKKEELERlKKRLTGLTPEKLEKELEELE-KAKEEIEEEISK----ITARIGELKK 419
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  443 EIERREAAKQELERQRRL------EWERIRRQELLNQKNRE----QEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDV 512
Cdd:PRK03918  420 EIKELKKAIEELKKAKGKcpvcgrELTEEHRKELLEEYTAElkriEKELKEIEEKERKLRKELRELEKVLKKESELIKLK 499
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  513 RLKKQTQKTELEVldKQCDLEimEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQ-FSNTPDSGVSLLHKKSLEKQEL 591
Cdd:PRK03918  500 ELAEQLKELEEKL--KKYNLE--ELEKKAEEYEKLKEKLIKLKGEIKSLKKELEKLEeLKKKLAELEKKLDELEEELAEL 575
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  592 CQRLKEQLDALEKETASKLSEMDSYNNQlkcgnmddsvlqcllsllsclnnlFLLLK----ELRETCNTQQLALEQLYKI 667
Cdd:PRK03918  576 LKELEELGFESVEELEERLKELEPFYNE------------------------YLELKdaekELEREEKELKKLEEELDKA 631
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  668 KRD---KLKEIERKRLELIQ-KKKLEDEAARKAKQGKENLWKE--NLRREEEEKQKRLQE-EKTQEKIQEEERKAEEKQR 740
Cdd:PRK03918  632 FEElaeTEKRLEELRKELEElEKKYSEEEYEELREEYLELSRElaGLRAELEELEKRREEiKKTLEKLKEELEEREKAKK 711
                         410       420
                  ....*....|....*....|....*
gi 966980062  741 KDKDTLKVEEKQRETASVLVNYRAL 765
Cdd:PRK03918  712 ELEKLEKALERVEELREKVKKYKAL 736
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
1558-1669 8.79e-06

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 46.85  E-value: 8.79e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1558 YQARSQKtsgigrLMVHVIEATELKACKPNGKSNPYCEISM-------GSQSYTTRTIQDTLNPKWNFNCQFFIKD---- 1626
Cdd:cd04009    11 YRASEQS------LRVEILNARNLLPLDSNGSSDPFVKVELlprhlfpDVPTPKTQVKKKTLFPLFDESFEFNVPPeqcs 84
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062 1627 LYQDVLCLTLFDRDQFSPDDFLGRT-----EIPVAKIRTEQESKGPVT 1669
Cdd:cd04009    85 VEGALLLFTVKDYDLLGSNDFEGEAflplnDIPGVEDTSSAQGFGPLP 132
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
764-813 8.80e-06

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 44.42  E-value: 8.80e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSF-QGNFGWFPCNYV 813
Cdd:cd11812     4 ALYDYTANRSDELTIHRGDIIRVLYKD--NDNWWFGSLvNGQQGYFPANYV 52
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
986-1034 8.86e-06

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 44.66  E-value: 8.86e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKD-GE--WWTGSIGDRSGIFPSNYV 1034
Cdd:cd11836     2 YRALYAFEARNPDEISFQPGDIIQVDESQvAEpgWLAGELKGKTGWFPANYV 53
SH3_BAIAP2L2 cd11914
Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; ...
904-952 8.86e-06

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212847 [Multi-domain]  Cd Length: 59  Bit Score: 44.81  E-value: 8.86e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  904 QALCSWTAKKdNH--LNFSKHDIITVL--EQQENWWFGEVHGG--RGWFPKSYVK 952
Cdd:cd11914     4 RAIVSHPAGS-NPtlLRFNRGDIITVLvpEARNGWLYGKLEGSsrQGWFPEAYVK 57
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
1133-1182 9.17e-06

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 44.64  E-value: 9.17e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12076     4 TVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLK 53
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
1064-1114 9.17e-06

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 44.61  E-value: 9.17e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGElqarGKKRQKGWFPASHVKL 1114
Cdd:cd11819     8 YQAAEDNEISFVEGDIITQIEQIDEGWWLGV----NAKGQKGLFPANYVEL 54
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
1057-1114 9.66e-06

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 44.23  E-value: 9.66e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVKL 1114
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGK-----TGWFPSNYVKE 53
DUF4670 pfam15709
Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins ...
671-754 9.85e-06

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.


Pssm-ID: 464815 [Multi-domain]  Cd Length: 522  Bit Score: 50.34  E-value: 9.85e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   671 KLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERK-------AEEKQRKDK 743
Cdd:pfam15709  346 RRLEVERKRREQEEQRRLQQEQLERAEKMREELELEQQRRFEEIRLRKQRLEEERQRQEEEERKqrlqlqaAQERARQQQ 425
                           90
                   ....*....|...
gi 966980062   744 DTL--KVEEKQRE 754
Cdd:pfam15709  426 EEFrrKLQELQRK 438
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
902-953 1.06e-05

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 44.26  E-value: 1.06e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11782     1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYVQV 53
SH3_Sorbs2_2 cd11923
Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
1131-1183 1.06e-05

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212856 [Multi-domain]  Cd Length: 57  Bit Score: 44.52  E-value: 1.06e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVT--GLFPSNYVKM 1183
Cdd:cd11923     2 EAVAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGTNrqGIFPVSYVEV 56
SH3_ASPP2 cd11953
Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full ...
1132-1179 1.08e-05

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212886 [Multi-domain]  Cd Length: 57  Bit Score: 44.56  E-value: 1.08e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPD---WWQGEINGVTGLFPSN 1179
Cdd:cd11953     3 VYALWDYEGESDDELSFKEGDCMTILRREDEDeteWWWARLNDKEGYVPRN 53
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
760-814 1.13e-05

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212930 [Multi-domain]  Cd Length: 56  Bit Score: 44.18  E-value: 1.13e-05
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gi 966980062  760 VNYRALYPFEARNHDEMSFNSG-DIIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 814
Cdd:cd11997     2 VRVRALYDYTGQEADELSFKAGeELLKIGEED--EQGWCKGRLLsGRIGLYPANYVE 56
SH3_GRAF3 cd12066
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is ...
763-814 1.13e-05

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212999  Cd Length: 55  Bit Score: 44.28  E-value: 1.13e-05
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gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIgEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12066     3 KAMYSCKAEHSHELSFPQGAIFSNVYPSV-EPGWLKATYEGKTGLVPENYVV 53
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
1135-1181 1.16e-05

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212978  Cd Length: 53  Bit Score: 44.12  E-value: 1.16e-05
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gi 966980062 1135 MYDYAANNEDELSFSKGQLINVMNK--DDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd12045     5 LWDCTGDQPDELSFKRGDTIYILSKeyNRFGWWVGEMKGTIGLVPKAYI 53
SH3_CASS4 cd12000
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ...
1134-1179 1.18e-05

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212933  Cd Length: 57  Bit Score: 44.48  E-value: 1.18e-05
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPD---WWQGEINGVTGLFPSN 1179
Cdd:cd12000     5 ALYDNKADCSDELAFRRGDILTVLEQNVPGsegWWKCLLHGRQGLAPAN 53
SH3_ASEF cd11973
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ...
1134-1183 1.18e-05

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212906 [Multi-domain]  Cd Length: 73  Bit Score: 45.01  E-value: 1.18e-05
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11973    22 ALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71
SH3_TXK cd11907
Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a ...
1131-1181 1.18e-05

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212840 [Multi-domain]  Cd Length: 55  Bit Score: 44.17  E-value: 1.18e-05
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN-GVTGLFPSNYV 1181
Cdd:cd11907     2 QVKALYDFLPREPSNLALKRAEEYLILEQYDPHWWKARDRyGNEGLIPSNYV 53
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
761-812 1.19e-05

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 44.11  E-value: 1.19e-05
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gi 966980062  761 NYRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQ--GNFGWFPCNY 812
Cdd:cd11845     1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGD--WWLARHLstGKEGYIPSNY 52
SH3_ASEF cd11973
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ...
903-953 1.23e-05

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212906 [Multi-domain]  Cd Length: 73  Bit Score: 44.62  E-value: 1.23e-05
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11973    20 AEALWDHVTMDDQELGFKAGDVIEVMDaTNKEWWWGRVLDSEGWFPASFVRL 71
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
1567-1655 1.23e-05

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 46.49  E-value: 1.23e-05
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gi 966980062 1567 GIGRLMVHVIEATELkackpNG----KSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQ-DVLCLTLFDRDQ 1641
Cdd:cd04032    26 GLATLTVTVLRATGL-----WGdyftSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFGSVELSPgGKLRFEVWDRDN 100
                          90
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gi 966980062 1642 FSPDDFLGRTEIPV 1655
Cdd:cd04032   101 GWDDDLLGTCSVVP 114
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
999-1034 1.25e-05

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212898 [Multi-domain]  Cd Length: 57  Bit Score: 44.23  E-value: 1.25e-05
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gi 966980062  999 DLTFTEGEEILVT-QKDGEWWTGSIG---DRSGIFPSNYV 1034
Cdd:cd11965    15 ELTFVEGEVIIVTgEEDQEWWIGHIEgqpERKGVFPVSFV 54
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
987-1036 1.27e-05

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 43.87  E-value: 1.27e-05
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gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYVEI 53
CCDC47 pfam07946
PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of ...
682-754 1.29e-05

PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins. CCDC47 is required to maintain the stability of Asterix. CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis. It is also involved in the regulation of calcium ion homeostasis in the ER, being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway.


Pssm-ID: 462322  Cd Length: 323  Bit Score: 49.10  E-value: 1.29e-05
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gi 966980062   682 LIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAE----EKQRkdkdtlKVEEKQRE 754
Cdd:pfam07946  248 LAKRAKLRPEALKKAKKTREEEIEKIKKAAEEERAEEAQEKKEEAKKKEREEKLAklspEEQR------KYEEKERK 318
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
986-1036 1.33e-05

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212941 [Multi-domain]  Cd Length: 56  Bit Score: 44.33  E-value: 1.33e-05
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTG---SIGdRSGIFPSNYVKP 1036
Cdd:cd12008     2 FVALYDYESRTETDLSFKKGERLqIVNNTEGDWWLAhslTTG-QTGYIPSNYVAP 55
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
1063-1113 1.34e-05

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212713 [Multi-domain]  Cd Length: 57  Bit Score: 44.24  E-value: 1.34e-05
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gi 966980062 1063 AYVASGSEQLSLAPGQLI-LILKKNTSGWWQGELQargKKRQKGWFPASHVK 1113
Cdd:cd11779     8 PHAAGGETQLSFEEGDVItLLGPEPRDGWHYGENE---RSGRRGWFPIAYTE 56
SH3_BCAR1 cd12001
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ...
900-956 1.34e-05

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212934  Cd Length: 68  Bit Score: 44.65  E-value: 1.34e-05
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gi 966980062  900 NLKAQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKIIPG 956
Cdd:cd12001     2 NVLAKALYDNVAESPDELSFRKGDIMTVLERDtqglDGWWLCSLHGRQGIVPGNRLKILVG 62
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
901-952 1.36e-05

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 44.23  E-value: 1.36e-05
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gi 966980062  901 LKAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11920     1 LPARAVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYVE 53
SH3_Eve1_2 cd11815
Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
987-1035 1.41e-05

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212749 [Multi-domain]  Cd Length: 52  Bit Score: 44.09  E-value: 1.41e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11815     3 VVLHDFPAEHSDDLSLNSGEIVYLLEKiDTEWYRGKCKNTTGIFPANHVK 52
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
902-953 1.48e-05

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 43.88  E-value: 1.48e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLE---QQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11875     1 KARVLFDYEAENEDELTLREGDIVTILSkdcEDKGWWKGELNGKRGVFPDNFVEP 55
sbcc TIGR00618
exonuclease SbcC; All proteins in this family for which functions are known are part of an ...
362-740 1.49e-05

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129705 [Multi-domain]  Cd Length: 1042  Bit Score: 49.97  E-value: 1.49e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   362 TFEDKRKAnyeRGNMELEKRRQALV-----EQQQREAERKAQKEKE--EWERKQRELQEQEWKKQLELEK---RLEKQRE 431
Cdd:TIGR00618  185 EFAKKKSL---HGKAELLTLRSQLLtlctpCMPDTYHERKQVLEKElkHLREALQQTQQSHAYLTQKREAqeeQLKKQQL 261
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   432 LERQREEERRKEIERREAAKQELERQRRLEWERI-RRQELLNQKNREQEEI-VRLNSKKKSLHLELEALNGKHQQisgrl 509
Cdd:TIGR00618  262 LKQLRARIEELRAQEAVLEETQERINRARKAAPLaAHIKAVTQIEQQAQRIhTELQSKMRSRAKLLMKRAAHVKQ----- 336
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   510 qdvRLKKQTQKTELEVLDKQCDLeimeikqlqQELQEYQNKLIYLVPEKQL-LNERIKNMQFSNTPDsgvsllhkksLEK 588
Cdd:TIGR00618  337 ---QSSIEEQRRLLQTLHSQEIH---------IRDAHEVATSIREISCQQHtLTQHIHTLQQQKTTL----------TQK 394
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   589 QELCQRLKEQLDALEKETASKLSEmdsynnqlkcgnmdDSVLQCLlsllsclnnlfllLKELRETCNTQQLALEQlykik 668
Cdd:TIGR00618  395 LQSLCKELDILQREQATIDTRTSA--------------FRDLQGQ-------------LAHAKKQQELQQRYAEL----- 442
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966980062   669 rdKLKEIERKRLELIQKKKLEDEAARKAKQGKENLW-KENLRREEEEKQKrlQEEKTQEKIQEEERKAEEKQR 740
Cdd:TIGR00618  443 --CAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQtKEQIHLQETRKKA--VVLARLLELQEEPCPLCGSCI 511
SH3_Tec cd11905
Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a ...
1132-1181 1.52e-05

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212838 [Multi-domain]  Cd Length: 56  Bit Score: 44.03  E-value: 1.52e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG-EINGVTGLFPSNYV 1181
Cdd:cd11905     3 VVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKArDKYGKEGYIPSNYV 53
SH3_SH3RF1_1 cd11927
First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ...
763-814 1.54e-05

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212860  Cd Length: 54  Bit Score: 43.79  E-value: 1.54e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11927     4 KALYNYEGKEPGDLKFSKGDIIilrrQVDEN------WYHGEVNGIHGFFPTNFVQ 53
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
764-814 1.55e-05

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212881 [Multi-domain]  Cd Length: 54  Bit Score: 44.04  E-value: 1.55e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11948     4 ALYSFQATESDELPFQKGDILKILNME-DDQNWYKAELQGREGYIPKNYIK 53
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
764-813 1.55e-05

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 43.91  E-value: 1.55e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11828     4 ALWDHVTMDPEELGFKAGDVIEVLDMS--DKDWWWGSIRDEEGWFPASFV 51
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
903-952 1.55e-05

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 43.77  E-value: 1.55e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ--QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11830     2 AKARYDFCARDMRELSLKEGDVVKIYNKkgQQGWWRGEINGRIGWFPSTYVE 53
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
766-813 1.58e-05

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 43.87  E-value: 1.58e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  766 YPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKC--SDGWWRGSYNGQVGWFPSNYV 53
MAP7 pfam05672
MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is ...
379-481 1.61e-05

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.


Pssm-ID: 461709 [Multi-domain]  Cd Length: 153  Bit Score: 46.57  E-value: 1.61e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   379 EKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQR 458
Cdd:pfam05672   18 EKRRQAREQREREEQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQRKAEEEAEEREQREQEEQE 97
                           90       100
                   ....*....|....*....|....*..
gi 966980062   459 RLEWER----IRRQELLNQKNREQEEI 481
Cdd:pfam05672   98 RLQKQKeeaeAKAREEAERQRQEREKI 124
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
900-951 1.61e-05

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 43.87  E-value: 1.61e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  900 NLKAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11901     1 NLPAYVKFNYTAEREDELSLVKGTKVIVMEKcSDGWWRGSYNGQVGWFPSNYV 53
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
1569-1669 1.62e-05

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 45.32  E-value: 1.62e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSN----PYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDLYQDV-LCLTLFDRDQFS 1643
Cdd:cd04039     1 GVVFMEIKSITDLPPLKNMTRTGfdmdPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYPHEKNFdIQFKVLDKDKFS 80
                          90       100
                  ....*....|....*....|....*.
gi 966980062 1644 PDDFLGRTEIPVAKIRTEQESKGPVT 1669
Cdd:cd04039    81 FNDYVATGSLSVQELLNAAPQPDPET 106
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
987-1036 1.66e-05

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212817 [Multi-domain]  Cd Length: 56  Bit Score: 43.85  E-value: 1.66e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGE----WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11884     3 VAVRAYITRDQTLLSFHKGDVIKLLPKEGPldpgWLFGTLDGRSGAFPKEYVQP 56
SH3_Tec cd11905
Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a ...
984-1037 1.68e-05

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212838 [Multi-domain]  Cd Length: 56  Bit Score: 43.65  E-value: 1.68e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  984 EEYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSigDR---SGIFPSNYVKPK 1037
Cdd:cd11905     1 EIVVAMYDFQPTEPHDLRLETGEEYVILEKnDVHWWKAR--DKygkEGYIPSNYVTGK 56
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
1064-1112 1.68e-05

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 43.65  E-value: 1.68e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELqARGkkrQKGWFPASHV 1112
Cdd:cd11812     8 YTANRSDELTIHRGDIIRVLYKDNDNWWFGSL-VNG---QQGYFPANYV 52
SH3_MPP5 cd12036
Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); ...
1132-1178 1.73e-05

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212969  Cd Length: 63  Bit Score: 43.94  E-value: 1.73e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1132 VIAMYDYaaNNEDE---------LSFSKGQLINVMNKDDPDWWQGEING------VTGLFPS 1178
Cdd:cd12036     2 VRAHFDY--DPEDDpyipcrelgLSFQKGDILHVISQEDPNWWQAYREGeednqsLAGLIPS 61
SH3_MPP6 cd12038
Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); ...
1143-1181 1.76e-05

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212971  Cd Length: 61  Bit Score: 43.90  E-value: 1.76e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 966980062 1143 EDELSFSKGQLINVMNKDDPDWWQG---EINGVTGLFPSNYV 1181
Cdd:cd12038    20 EAGLKFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFL 61
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
1570-1660 1.77e-05

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 45.77  E-value: 1.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELkackPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNfncQFFI--KDLYQ-DVLCLTLFDRDqFSPDD 1646
Cdd:cd08378     1 YLYVRVVKARGL----PANSNDPVVEVKLGNYKGSTKAIERTSNPEWN---QVFAfsKDRLQgSTLEVSVWDKD-KAKDD 72
                          90
                  ....*....|....
gi 966980062 1647 FLGRTEIPVAKIRT 1660
Cdd:cd08378    73 FLGGVCFDLSEVPT 86
SH3_Nck_1 cd11765
First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
1132-1181 1.82e-05

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212699 [Multi-domain]  Cd Length: 51  Bit Score: 43.56  E-value: 1.82e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNkDDPDWWQGE-INGVTGLFPSNYV 1181
Cdd:cd11765     2 VVAKYDYTAQGDQELSIKKNEKLTLLD-DSKHWWKVQnSSNQTGYVPSNYV 51
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
762-813 1.85e-05

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212925  Cd Length: 52  Bit Score: 43.46  E-value: 1.85e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTiGEpgWLYGSFQGNFGWFPCNYV 813
Cdd:cd11992     2 YIALYPYSSSEPGDLTFNEGEEILVTQKD-GE--WWTGSIEDRTGIFPSNYV 50
ARGLU pfam15346
Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is ...
666-753 1.86e-05

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.


Pssm-ID: 405931 [Multi-domain]  Cd Length: 151  Bit Score: 46.58  E-value: 1.86e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   666 KIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENL-------RREEEEKQKRLqEEKTQEKIQEEERKAEEK 738
Cdd:pfam15346   49 IMEKQVLEELEREREAELEEERRKEEEERKKREELERILEENNrkieeaqRKEAEERLAML-EEQRRMKEERQRREKEEE 127
                           90
                   ....*....|....*
gi 966980062   739 QRKDKDTLKVEEKQR 753
Cdd:pfam15346  128 EREKREQQKILNKKN 142
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
988-1034 1.89e-05

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 43.80  E-value: 1.89e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  988 ALYPYSSVEPG-DLTFTEGEEILVTQK------DGEWWTGSIGD-RSGIFPSNYV 1034
Cdd:cd11771     4 ALYDFTPENPEmELSLKKGDIVAVLSKtdplgrDSEWWKGRTRDgRIGWFPSNYV 58
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
763-812 1.93e-05

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 43.42  E-value: 1.93e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKtiGEPGW-----LYGSFQGNFGWFPCNY 812
Cdd:cd11883     3 VALYDFTPKSKNQLSFKAGDIIYVLNK--DPSGWwdgviISSSGKVKRGWFPSNY 55
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1570-1663 1.94e-05

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 45.64  E-value: 1.94e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1570 RLMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWNFNCQFFIKDlYQDVLCLTLFDRD--------- 1640
Cdd:cd04027     2 KISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDEDddiksrlkq 80
                          90       100
                  ....*....|....*....|....*
gi 966980062 1641 QFS--PDDFLGRTEIPVAKIRTEQE 1663
Cdd:cd04027    81 KFTreSDDFLGQTIIEVRTLSGEMD 105
DUF4670 pfam15709
Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins ...
352-484 1.94e-05

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.


Pssm-ID: 464815 [Multi-domain]  Cd Length: 522  Bit Score: 49.18  E-value: 1.94e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   352 EEEPQKKLPVTFEDKRKANYERGNMELEKRRQALVEQQQREaerKAQKEKEEWERKQRELQEQewKKQLELEK-RLEKQR 430
Cdd:pfam15709  379 ELEQQRRFEEIRLRKQRLEEERQRQEEEERKQRLQLQAAQE---RARQQQEEFRRKLQELQRK--KQQEEAERaEAEKQR 453
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966980062   431 ELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQKNREQEEIVRL 484
Cdd:pfam15709  454 QKELEMQLAEEQKRLMEMAEEERLEYQRQKQEAEEKARLEAEERRQKEEEAARL 507
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
985-1035 1.96e-05

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 43.52  E-value: 1.96e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11824     1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYLE 52
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
986-1036 2.03e-05

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 43.51  E-value: 2.03e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK-----DGEWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11800     2 YYALYTFEARSPGELSVTEGQVVTVLEKhdlkgNPEWWLVEDRGKQGYVPSNYLAK 57
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
902-953 2.04e-05

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 43.47  E-value: 2.04e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ--ENWWFGE-VHGGRGWFPKSYVKI 953
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGRnSRGEVGLFPSSYVEI 55
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1064-1114 2.12e-05

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 43.40  E-value: 2.12e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHVKL 1114
Cdd:cd11995     9 YTAQNDDELAFSKGQIINVLNKEDPDWWKGELNG-----QVGLFPSNYVKL 54
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
902-951 2.29e-05

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212730  Cd Length: 51  Bit Score: 43.11  E-value: 2.29e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWF-GEVHGGRGWFPKSYV 951
Cdd:cd11796     1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFrGELNGRRGIFPEGFV 51
SH3_Lck cd12005
Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of ...
1131-1183 2.32e-05

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212938 [Multi-domain]  Cd Length: 54  Bit Score: 43.27  E-value: 2.32e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKdDPDWWQGE--INGVTGLFPSNYVKM 1183
Cdd:cd12005     1 LVVALYSYEPSHDGDLGFEKGEKLRILEQ-SGEWWKAQslTTGQEGFIPFNFVAK 54
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
902-953 2.34e-05

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212881 [Multi-domain]  Cd Length: 54  Bit Score: 43.27  E-value: 2.34e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11948     1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIKV 54
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
398-747 2.35e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 49.28  E-value: 2.35e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   398 QKEKEEWERKQRELQEQEWKKQLELEKRLEKQRelerqreeerrkeierreaAKQELERQRRLEWERIRRQ--ELLNQKN 475
Cdd:TIGR02168  676 RREIEELEEKIEELEEKIAELEKALAELRKELE-------------------ELEEELEQLRKELEELSRQisALRKDLA 736
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   476 REQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDkqcdleimeikqlqQELQEYQNkliylv 555
Cdd:TIGR02168  737 RLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELE--------------AQIEQLKE------ 796
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   556 pEKQLLNERIKNMQfsntpdSGVSLLHKKSLEKQELCQRLKEQLDALEK------ETASKLSE-MDSYNnqlkcGNMDDS 628
Cdd:TIGR02168  797 -ELKALREALDELR------AELTLLNEEAANLRERLESLERRIAATERrledleEQIEELSEdIESLA-----AEIEEL 864
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   629 VLQCLLSLLSCLnnlflLLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLELIQKKKledeaARKAKQGKENLWKENL 708
Cdd:TIGR02168  865 EELIEELESELE-----ALLNERASLEEALALLRSELEELSEELRELESKRSELRRELE-----ELREKLAQLELRLEGL 934
                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 966980062   709 RREEEEKQKRLQEE--KTQEKIQEEERKAEEKQRKDKDTLK 747
Cdd:TIGR02168  935 EVRIDNLQERLSEEysLTLEEAEALENKIEDDEEEARRRLK 975
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
1064-1113 2.36e-05

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 43.39  E-value: 2.36e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILIL-KKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd11976     8 FCARDRSELSLKEGDIIKILnKKGQQGWWRGEIYGR-----VGWFPANYVE 53
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
763-814 2.44e-05

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 43.11  E-value: 2.44e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11782     3 RAKYNFNADTGVELSFRKGDVItltrRVDEN------WYEGRIGGRQGIFPVSYVQ 52
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
377-747 2.53e-05

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 49.30  E-value: 2.53e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   377 ELEKRRQALVEQQQR--EAERKAQKEKEEWERKQRELQEqewkkqleLEKRLEKQRELERQREEERRKEIERREAAKQEL 454
Cdd:TIGR02169  689 ELSSLQSELRRIENRldELSQELSDASRKIGEIEKEIEQ--------LEQEEEKLKERLEELEEDLSSLEQEIENVKSEL 760
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   455 ERqrrLEWERIRRQELLNQKNREQEEIVR--LNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKqcdl 532
Cdd:TIGR02169  761 KE---LEARIEELEEDLHKLEEALNDLEArlSHSRIPEIQAELSKLEEEVSRIEARLREIEQKLNRLTLEKEYLEK---- 833
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   533 EIMEIKqlqqelqeyqNKLIYLVPEKQLLNERIKNMQfsntpdsgvsllhkksLEKQELCQRLKE---QLDALEKETASK 609
Cdd:TIGR02169  834 EIQELQ----------EQRIDLKEQIKSIEKEIENLN----------------GKKEELEEELEEleaALRDLESRLGDL 887
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   610 LSEMDSYNNQLKcgNMDDSVLQcllsllsclnnlfllLKELRETCNTQQLALEQLYKIKRDKLKEIERKR---------- 679
Cdd:TIGR02169  888 KKERDELEAQLR--ELERKIEE---------------LEAQIEKKRKRLSELKAKLEALEEELSEIEDPKgedeeipeee 950
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062   680 --LELIQKKKLEDEAARKAkqgkenLWKENLRREEE--EKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLK 747
Cdd:TIGR02169  951 lsLEDVQAELQRVEEEIRA------LEPVNMLAIQEyeEVLKRLDELKEKRAKLEEERKAILERIEEYEKKK 1016
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
1064-1112 2.54e-05

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 43.39  E-value: 2.54e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTS-----GWWQGELQARgkkrqKGWFPASHV 1112
Cdd:cd12058     8 YEASGEDELSLRRGDVVEVLSQDAAvsgddGWWAGKIRHR-----LGIFPANYV 56
SH3_TXK cd11907
Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a ...
987-1034 2.55e-05

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212840 [Multi-domain]  Cd Length: 55  Bit Score: 43.40  E-value: 2.55e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSigDR---SGIFPSNYV 1034
Cdd:cd11907     4 KALYDFLPREPSNLALKRAEEYLILEQyDPHWWKAR--DRygnEGLIPSNYV 53
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
902-953 2.56e-05

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 43.25  E-value: 2.56e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGE-VHGGRGWFPKSYVKI 953
Cdd:cd11962     1 RAVVLYDYEKDEDNEIELVEGEIVTNIEMvDEDWWMGTnSKGESGLFPSNYVEL 54
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
986-1036 2.60e-05

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 43.50  E-value: 2.60e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTG---SIGDrSGIFPSNYVKP 1036
Cdd:cd12006     3 FVALYDYEARTEDDLSFHKGEKFqILNSSEGDWWEArslTTGE-TGYIPSNYVAP 56
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
364-732 2.61e-05

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 49.30  E-value: 2.61e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   364 EDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQ---RELQEQEWKKQLELEKRLEKQRELERQREEER 440
Cdd:TIGR02169  170 RKKEKALEELEEVEENIERLDLIIDEKRQQLERLRREREKAERYQallKEKREYEGYELLKEKEALERQKEAIERQLASL 249
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   441 RKEierrEAAKQELERQRRLEWERIRRqeLLNQKNRE-----QEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDvrLK 515
Cdd:TIGR02169  250 EEE----LEKLTEEISELEKRLEEIEQ--LLEELNKKikdlgEEEQLRVKEKIGELEAEIASLERSIAEKERELED--AE 321
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   516 KQTQKTELEvLDKQcDLEIMEIKQLQQELQEYQNKLIylvpekqllnERIKNMQfsNTPDSGVSLLHKKSLEKQELCQRL 595
Cdd:TIGR02169  322 ERLAKLEAE-IDKL-LAEIEELEREIEEERKRRDKLT----------EEYAELK--EELEDLRAELEEVDKEFAETRDEL 387
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   596 K---EQLDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLlsllsclnnlfllLKELREtcntQQLALEQLYKIKRDKL 672
Cdd:TIGR02169  388 KdyrEKLEKLKREINELKRELDRLQEELQRLSEELADLNAA-------------IAGIEA----KINELEEEKEDKALEI 450
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966980062   673 KEIERKRLELIQKKKledeaarKAKQGKENLwKENLRREEEE---KQKRLQEEKTQEKIQEEE 732
Cdd:TIGR02169  451 KKQEWKLEQLAADLS-------KYEQELYDL-KEEYDRVEKElskLQRELAEAEAQARASEER 505
SH3_Vinexin_2 cd11924
Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 ...
985-1035 2.62e-05

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212857  Cd Length: 56  Bit Score: 43.41  E-value: 2.62e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIG--DRSGIFPSNYVK 1035
Cdd:cd11924     2 EAVAQYTFKGDLEVELSFRKGEHIcLIRKVNENWYEGRITgtGRQGIFPASYVQ 55
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
335-621 2.68e-05

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 49.30  E-value: 2.68e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   335 KQIDSINGTLPSYQKIQEE--EPQKKLPVTFEDKrKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQ 412
Cdd:TIGR02169  723 KEIEQLEQEEEKLKERLEEleEDLSSLEQEIENV-KSELKELEARIEELEEDLHKLEEALNDLEARLSHSRIPEIQAELS 801
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   413 EQEwkkqlELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWERI----RRQELLNQKNREQEEIVR----- 483
Cdd:TIGR02169  802 KLE-----EEVSRIEARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKEQIksieKEIENLNGKKEELEEELEeleaa 876
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   484 ----------LNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDlEIMEIKQLQQELQEYQNKLIY 553
Cdd:TIGR02169  877 lrdlesrlgdLKKERDELEAQLRELERKIEELEAQIEKKRKRLSELKAKLEALEEELS-EIEDPKGEDEEIPEEELSLED 955
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062   554 LVPEKQLLNERIKNMQFSNTpdsgvsllhkKSLEKQELCQR----LKEQLDALEKETASKLSEMDSYNNQLK 621
Cdd:TIGR02169  956 VQAELQRVEEEIRALEPVNM----------LAIQEYEEVLKrldeLKEKRAKLEEERKAILERIEEYEKKKR 1017
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
991-1035 2.83e-05

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 43.10  E-value: 2.83e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  991 PYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDR-----SGIFPSNYVK 1035
Cdd:cd11839     7 PFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQARgkkrqIGWFPANYVK 57
PRK02224 PRK02224
DNA double-strand break repair Rad50 ATPase;
364-756 2.85e-05

DNA double-strand break repair Rad50 ATPase;


Pssm-ID: 179385 [Multi-domain]  Cd Length: 880  Bit Score: 48.88  E-value: 2.85e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  364 EDKRKANYERGNMEL-----EKRRQALVEQQQ-----REAERKAQKEKEEWERKQRELQEQewkkQLELEKRLEKQRELE 433
Cdd:PRK02224  227 EQREQARETRDEADEvleehEERREELETLEAeiedlRETIAETEREREELAEEVRDLRER----LEELEEERDDLLAEA 302
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  434 RQREEERRKEIERREA-AKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKhqqisgrLQDV 512
Cdd:PRK02224  303 GLDDADAEAVEARREElEDRDEELRDRLEECRVAAQAHNEEAESLREDADDLEERAEELREEAAELESE-------LEEA 375
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  513 RLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFS------------------NTP 574
Cdd:PRK02224  376 REAVEDRREEIEELEEEIEELRERFGDAPVDLGNAEDFLEELREERDELREREAELEATlrtarerveeaealleagKCP 455
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  575 DSG--------VSLLHKKSLEKQELCQRL---KEQLDALEK--ETASKLSEMDSYNNQLKcGNMDDSVLqcllsllscln 641
Cdd:PRK02224  456 ECGqpvegsphVETIEEDRERVEELEAELedlEEEVEEVEErlERAEDLVEAEDRIERLE-ERREDLEE----------- 523
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  642 nlflLLKELRETCNTQQLALEQLYKIKRDKLKEIERKRlELIQKKKLEDEAARKA-----------KQGKENLWK----- 705
Cdd:PRK02224  524 ----LIAERRETIEEKRERAEELRERAAELEAEAEEKR-EAAAEAEEEAEEAREEvaelnsklaelKERIESLERirtll 598
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  706 ---ENLRREEE---EKQKRLQEEKTQEKiqeeERKAEEKQRKDKDTLKVEEKQRETA 756
Cdd:PRK02224  599 aaiADAEDEIErlrEKREALAELNDERR----ERLAEKRERKRELEAEFDEARIEEA 651
SH3_GRAF cd12064
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also ...
763-814 2.88e-05

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212997  Cd Length: 56  Bit Score: 43.18  E-value: 2.88e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQvDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12064     4 KALYACKAEHDSELSFTAGTVFD-NVHPSQEPGWLEGTLNGKTGLIPENYVE 54
MAP7 pfam05672
MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is ...
676-756 2.88e-05

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.


Pssm-ID: 461709 [Multi-domain]  Cd Length: 153  Bit Score: 45.80  E-value: 2.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   676 ERKRLELIQKKKLEDEaaRKAKQGKENLWKENLRREEEEKQKRLQEE----KTQEKIQEEERK------AEEKQRKDKDT 745
Cdd:pfam05672   18 EKRRQAREQREREEQE--RLEKEEEERLRKEELRRRAEEERARREEEarrlEEERRREEEERQrkaeeeAEEREQREQEE 95
                           90
                   ....*....|.
gi 966980062   746 LKVEEKQRETA 756
Cdd:pfam05672   96 QERLQKQKEEA 106
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
985-1034 2.92e-05

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 43.02  E-value: 2.92e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKssDG-WWRGECNGQVGWFPSNYV 51
SH3_ARHGEF37_C2 cd11941
Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 ...
1131-1181 3.08e-05

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212874  Cd Length: 57  Bit Score: 42.98  E-value: 3.08e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDD----PDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11941     1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDkkgsPEWSLVEVNGQRGYVPSSYL 55
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
766-813 3.12e-05

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 43.07  E-value: 3.12e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  766 YPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKC--SDGWWRGSYNGQIGWFPSNYV 52
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
984-1035 3.13e-05

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 43.07  E-value: 3.13e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  984 EEYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11972     3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKnDDGWYEGVMNGVTGLFPGNYVE 55
SH3_Lyn cd12004
Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of ...
1132-1181 3.16e-05

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212937 [Multi-domain]  Cd Length: 56  Bit Score: 43.06  E-value: 3.16e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMnKDDPDWWQGE--INGVTGLFPSNYV 1181
Cdd:cd12004     2 VVALYPYDGIHEDDLSFKKGEKLKVI-EEHGEWWKARslTTKKEGFIPSNYV 52
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
915-953 3.17e-05

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 43.03  E-value: 3.17e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062  915 NHLNFSKHDIITVL------EQQENWWFGEVHGGR-GWFPKSYVKI 953
Cdd:cd11771    15 MELSLKKGDIVAVLsktdplGRDSEWWKGRTRDGRiGWFPSNYVEV 60
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
766-816 3.18e-05

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212986  Cd Length: 56  Bit Score: 42.91  E-value: 3.18e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  766 YPFEARNHDEMSFNSGDIIQvDEKTIGEPGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd12053     6 YDYDAVHEDELTIRVGEIIR-NVKKLEEEGWLEGELNGRRGMFPDNFVKEI 55
SH3_SLAP-like cd11848
Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited ...
987-1034 3.23e-05

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212782  Cd Length: 55  Bit Score: 42.95  E-value: 3.23e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTG---SIGDRSGIfPSNYV 1034
Cdd:cd11848     3 VALGDYPSGGPAELSLRLGEPLTIVSDEGDWWKVlseVTGRESYI-PSVHV 52
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
413-766 3.24e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 48.91  E-value: 3.24e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  413 EQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQRR----LEWERIRRQELLNQKNREQEEIVRLNSKK 488
Cdd:PRK03918  161 ENAYKNLGEVIKEIKRRIERLEKFIKRTENIEELIKEKEKELEEVLReineISSELPELREELEKLEKEVKELEELKEEI 240
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  489 KSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDlEIMEIKQLQQE-------LQEYQNKLIYLVPEKQLL 561
Cdd:PRK03918  241 EELEKELESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVK-ELKELKEKAEEyiklsefYEEYLDELREIEKRLSRL 319
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  562 NERIKNMQfsntpdSGVSLLHKKSLEKQELCQRLKEQLDALEK---------ETASKLSEMDSYNNQLKCGNMDDsvlqc 632
Cdd:PRK03918  320 EEEINGIE------ERIKELEEKEERLEELKKKLKELEKRLEEleerhelyeEAKAKKEELERLKKRLTGLTPEK----- 388
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  633 llsllsclnnlflLLKELREtcntqqlaLEQLYKIKRDKLKEIERKRLELIQKKK-LED--EAARKAKqGKENLWKENLr 709
Cdd:PRK03918  389 -------------LEKELEE--------LEKAKEEIEEEISKITARIGELKKEIKeLKKaiEELKKAK-GKCPVCGREL- 445
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062  710 reEEEKQKRLQEEKTQE--KIQEEERKAEEKQRKDKDTLKVEEKQRETASVLVNYRALY 766
Cdd:PRK03918  446 --TEEHRKELLEEYTAElkRIEKELKEIEEKERKLRKELRELEKVLKKESELIKLKELA 502
SH3_Shank cd11832
Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank ...
1131-1178 3.29e-05

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212766  Cd Length: 50  Bit Score: 42.81  E-value: 3.29e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPS 1178
Cdd:cd11832     1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
988-1035 3.29e-05

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 43.01  E-value: 3.29e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11976     4 ARYDFCARDRSELSLKEGDIIKILNKKGQqgWWRGEIYGRVGWFPANYVE 53
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
763-813 3.34e-05

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 42.87  E-value: 3.34e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11951     3 QAQYDFSAEDPSQLSFRRGDIIEVLDCP--DPNWWRGRISGRVGFFPRNYV 51
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
763-813 3.35e-05

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 43.08  E-value: 3.35e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11963     5 RALYDFEAVEDNELTFKHGEIIIVLDDS--DANWWKGENHRGVGLFPSNFV 53
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
1437-1539 3.35e-05

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 44.07  E-value: 3.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1437 HSGKLYKT-----KSNKELHGFLFNDFLLltymvkqfavssgseklFSSKSNAQFKMYKTPIFLNEVLVKLPTDPSSDEP 1511
Cdd:cd00821     1 KEGYLLKRgggglKSWKKRWFVLFEGVLL-----------------YYKSKKDSSYKPKGSIPLSGILEVEEVSPKERPH 63
                          90       100
                  ....*....|....*....|....*....
gi 966980062 1512 VFHISH-IDRVYTLRTDNINERTAWVQKI 1539
Cdd:cd00821    64 CFELVTpDGRTYYLQADSEEERQEWLKAL 92
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
763-813 3.38e-05

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 42.73  E-value: 3.38e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11804     3 VAKHDFKATAEDELSFKKGSILKVLNME-DDPNWYKAELDGKEGLIPKNYI 52
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1568-1691 3.39e-05

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 48.99  E-value: 3.39e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1568 IGRLMVHVIEATELKACKP--NGKSNPYceISMGSQSY---TTRTIQDTLNPKWNFNCQFFIKDLyQDVLCLTLFDRDQF 1642
Cdd:COG5038   435 IGVVEVKIKSAEGLKKSDStiNGTVDPY--ITVTFSDRvigKTRVKKNTLNPVWNETFYILLNSF-TDPLNLSLYDFNSF 511
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1643 SPDDFLGRTEIPVAKIRtEQESKGPVTRRLLLHEVPTGEvwVRFDLQLF 1691
Cdd:COG5038   512 KSDKVVGSTQLDLALLH-QNPVKKNELYEFLRNTKNVGR--LTYDLRFF 557
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
988-1036 3.43e-05

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212815 [Multi-domain]  Cd Length: 54  Bit Score: 42.67  E-value: 3.43e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11882     4 ALYACKAEDESELSFEPGQIITNVQPSDEpgWLEGTLNGRTGLIPENYVEF 54
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
1573-1663 3.44e-05

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 44.49  E-value: 3.44e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1573 VHVIEATELkackPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWN----FNCQFFIKDLYQDVLCLTLFDRDQFSPDDFL 1648
Cdd:cd04011     8 VRVIEARQL----VGGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNeyffFNFHESPDELFDKIIKISVYDSRSLRSDTLI 83
                          90
                  ....*....|....*
gi 966980062 1649 GRTEIPVAKIRTEQE 1663
Cdd:cd04011    84 GSFKLDVGTVYDQPD 98
SH3_MPP3 cd12039
Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); ...
1117-1178 3.53e-05

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212972  Cd Length: 62  Bit Score: 43.02  E-value: 3.53e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1117 PSSERATPafhpvCQviamydyaannEDELSFSKGQLINVMNKDDPDWWQ----GEINGVTGLFPS 1178
Cdd:cd12039    10 PYEDRAIP-----CQ-----------EAGLPFKRRDILEVVSQDDPTWWQakrvGDTNLRAGLIPS 59
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
1132-1181 3.61e-05

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 43.08  E-value: 3.61e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQ-GEINGVTGLFPSNYV 1181
Cdd:cd11908     3 VIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRvQDKNGHEGYVPSSYL 53
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
1133-1181 3.71e-05

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212858  Cd Length: 57  Bit Score: 43.06  E-value: 3.71e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEI--NGVTGLFPSNYV 1181
Cdd:cd11925     4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSlrTGVSGVFPGNYV 54
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
987-1035 3.84e-05

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 42.90  E-value: 3.84e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12073     4 VALYDYQGEGDDEISFDPQETITdIEMVDEGWWKGTCHGHRGLFPANYVE 53
ARGLU pfam15346
Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is ...
661-754 3.89e-05

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.


Pssm-ID: 405931 [Multi-domain]  Cd Length: 151  Bit Score: 45.43  E-value: 3.89e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   661 LEQLYKIKRDKLKEIERKRLElIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEkiqEEERKAEEKQR 740
Cdd:pfam15346   24 VEEELEKRKDEIEAEVERRVE-EARKIMEKQVLEELEREREAELEEERRKEEEERKKREELERILE---ENNRKIEEAQR 99
                           90
                   ....*....|....*.
gi 966980062   741 KDKDT--LKVEEKQRE 754
Cdd:pfam15346  100 KEAEErlAMLEEQRRM 115
SH3_Tks5_1 cd12074
First Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
1060-1112 4.19e-05

First Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the first SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213007 [Multi-domain]  Cd Length: 53  Bit Score: 42.78  E-value: 4.19e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1060 VTSAYVASGSEQLSLAPGQLILILKKNTSGWWqgelqARGKKRQKGWFPASHV 1112
Cdd:cd12074     4 VVSNYEKQENSEISLQAGEVVDVIEKNESGWW-----FVSTAEEQGWVPATYL 51
SH3_BCAR1 cd12001
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ...
1134-1183 4.39e-05

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212934  Cd Length: 68  Bit Score: 43.11  E-value: 4.39e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDP---DWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12001     7 ALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLHGRQGIVPGNRLKI 59
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
917-951 4.43e-05

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212817 [Multi-domain]  Cd Length: 56  Bit Score: 42.70  E-value: 4.43e-05
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 966980062  917 LNFSKHDIITVL----EQQENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11884    16 LSFHKGDVIKLLpkegPLDPGWLFGTLDGRSGAFPKEYV 54
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
903-953 4.45e-05

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 42.71  E-value: 4.45e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHG-GR----GWFPKSYVKI 953
Cdd:cd11839     2 AQVIAPFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQArGKkrqiGWFPANYVKL 58
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
1060-1113 4.55e-05

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 42.71  E-value: 4.55e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1060 VTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHVK 1113
Cdd:cd12076     5 VIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQG-----KEGWAPASYLK 53
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
905-951 4.59e-05

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 42.38  E-value: 4.59e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11806     4 AIADFVATDDSQLSFESGDKLLVLRKpSVDWWWAEHNGCCGYIPASHL 51
SH3_Shank cd11832
Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank ...
762-809 4.64e-05

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212766  Cd Length: 50  Bit Score: 42.42  E-value: 4.64e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFP 809
Cdd:cd11832     2 FIAVKSYSPQEEGEISLHKGDRVKV--LSIGEGGFWEGSVRGRTGWFP 47
CAF-1_p150 pfam11600
Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide ...
648-753 4.69e-05

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.


Pssm-ID: 402959 [Multi-domain]  Cd Length: 164  Bit Score: 45.45  E-value: 4.69e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   648 KELRETCNTQQLALEQLYKIKRDKLKEiERKRLE---LIQKKKLEDEAARKAKQGKENLWKENL-RREEEEKQK----RL 719
Cdd:pfam11600   10 QEEKEKQRLEKDKERLRRQLKLEAEKE-EKERLKeeaKAEKERAKEEARRKKEEEKELKEKERReKKEKDEKEKaeklRL 88
                           90       100       110
                   ....*....|....*....|....*....|....
gi 966980062   720 QEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQR 753
Cdd:pfam11600   89 KEEKRKEKQEALEAKLEEKRKKEEEKRLKEEEKR 122
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
901-952 4.80e-05

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 42.68  E-value: 4.80e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  901 LKAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 952
Cdd:cd12060     2 LVVKARFNFKQTNEDELSVCKGDIIYVTRVEEGgWWEGTLNGKTGWFPSNYVR 54
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
904-954 4.95e-05

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 42.58  E-value: 4.95e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQ---ENWWFGEVHGGRGWFPKSYVKII 954
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDcidAGWWEGELNGRRGVFPDNFVKLL 56
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
763-814 4.97e-05

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 42.34  E-value: 4.97e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKtigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11990     3 QALCSWTAKKDNHLNFSKNDIITVLEQ---QENWWFGEVHGGRGWFPKSYVK 51
SH3_Nck2_3 cd11903
Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
989-1034 4.98e-05

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212836 [Multi-domain]  Cd Length: 59  Bit Score: 42.74  E-value: 4.98e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  989 LYPYSSVEPGDLTFTEGEEILVTQK---DGEWW--TGSIGdRSGIFPSNYV 1034
Cdd:cd11903     6 LYPFSSVTEEELNFEKGETMEVIEKpenDPEWWkcKNSRG-QVGLVPKNYV 55
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
990-1034 5.04e-05

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 42.33  E-value: 5.04e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062  990 YPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKcsDG-WWRGSYNGQVGWFPSNYV 53
SH3_PACSIN_like cd11999
Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C ...
760-814 5.11e-05

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212932 [Multi-domain]  Cd Length: 56  Bit Score: 42.62  E-value: 5.11e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  760 VNYRALYPFEARNHDEMSFNSGD-IIQVDEKTigEPGWLYG-SFQGNFGWFPCNYVE 814
Cdd:cd11999     2 VRVRAVYDYTGQEPDELSFKAGEeLLKVEDED--EQGWCKGvTDGGAVGLYPANYVE 56
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
904-953 5.12e-05

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212837 [Multi-domain]  Cd Length: 57  Bit Score: 42.71  E-value: 5.12e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WW-FGEVHGGRGWFPKSYVKI 953
Cdd:cd11904     4 QALYPFSSSNDEELNFEKGEVMDVIEKPENdpeWWkCRKANGQVGLVPKNYVTV 57
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
1571-1673 5.35e-05

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 44.67  E-value: 5.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKpnGKSNPYCEISMGS--QSYTTRTIQDTLNPKWNfncQFFIKDLYQ--DVLCLTLFDRDQFSPDD 1646
Cdd:cd08678     1 LLVKNIKANGLSEAA--GSSNPYCVLEMDEppQKYQSSTQKNTSNPFWD---EHFLFELSPnsKELLFEVYDNGKKSDSK 75
                          90       100
                  ....*....|....*....|....*..
gi 966980062 1647 FLGRTEIPVAKIRteqesKGPVTRRLL 1673
Cdd:cd08678    76 FLGLAIVPFDELR-----KNPSGRQIF 97
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
988-1034 5.64e-05

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212777 [Multi-domain]  Cd Length: 53  Bit Score: 42.41  E-value: 5.64e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGE-WWTGSIGDRSGIFPSNYV 1034
Cdd:cd11843     4 ALYDYEGQESDELSFKAGDILTkLEEEDEQgWCKGRLDGRVGLYPANYV 52
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
1573-1651 5.64e-05

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 44.56  E-value: 5.64e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1573 VHVIEATELKACKPNGKSNPYCEISMGSQSY---TTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDFLG 1649
Cdd:cd04043     5 IRIVRAENLKADSSNGLSDPYVTLVDTNGKRriaKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCG 84

                  ..
gi 966980062 1650 RT 1651
Cdd:cd04043    85 RA 86
tolA PRK09510
cell envelope integrity inner membrane protein TolA; Provisional
656-749 5.64e-05

cell envelope integrity inner membrane protein TolA; Provisional


Pssm-ID: 236545 [Multi-domain]  Cd Length: 387  Bit Score: 47.49  E-value: 5.64e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  656 TQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKA----KQGKENLWK--ENLRREEEEKQKRLQEEKTQEKIQ 729
Cdd:PRK09510   87 QQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAEEAAKQAalkqKQAEEAAAKaaAAAKAKAEAEAKRAAAAAKKAAAE 166
                          90       100
                  ....*....|....*....|
gi 966980062  730 EEERKAEEKQRKDKDTLKVE 749
Cdd:PRK09510  167 AKKKAEAEAAKKAAAEAKKK 186
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
764-816 5.70e-05

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 42.69  E-value: 5.70e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd11972     7 AIYDYTKDKEDELSFQEGAIIYVIKKN--DDGWYEGVMNGVTGLFPGNYVESI 57
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
987-1033 6.22e-05

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 42.27  E-value: 6.22e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKD--GeWWTGSIGDRSGI-----FPSNY 1033
Cdd:cd11883     3 VALYDFTPKSKNQLSFKAGDIIYVLNKDpsG-WWDGVIISSSGKvkrgwFPSNY 55
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
1064-1113 6.27e-05

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 41.93  E-value: 6.27e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELqarGKKRQKgWFPASHVK 1113
Cdd:cd11825     8 YRAQRPDELSFCKHAIITNVEKEDGGWWRGDY---GGKKQK-WFPANYVE 53
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
904-954 6.34e-05

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 42.28  E-value: 6.34e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRG-WFPKSYVKII 954
Cdd:cd11970     7 KALFDYKAQREDELTFTKNAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVEEI 59
SH3_SH3RF1_3 cd11926
Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ...
1133-1181 6.41e-05

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212859 [Multi-domain]  Cd Length: 55  Bit Score: 42.26  E-value: 6.41e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEI--NGVTGLFPSNYV 1181
Cdd:cd11926     3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSmhTSKIGVFPGNYV 53
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
902-951 6.49e-05

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 42.02  E-value: 6.49e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11827     1 QCKALYAYDAQDTDELSFNEGDIIEILkEDPSGWWTGRLRGKEGLFPGNYV 51
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1059-1115 6.51e-05

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 42.19  E-value: 6.51e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1059 QVTSAYVASGSEQLSLAPGQLILILKKNT--SGWWQGELQARgkkrqKGWFPASHVKLL 1115
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDCidAGWWEGELNGR-----RGVFPDNFVKLL 56
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
1571-1658 6.54e-05

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 44.97  E-value: 6.54e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKACKPNGKSNPYCEISMGSQSYTTRTIQD-TLNPKWNFNCQFFIKDLYQDVLCLTLFDRDQFSPDDFLG 1649
Cdd:cd04019     2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQTrNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPLG 81

                  ....*....
gi 966980062 1650 RTEIPVAKI 1658
Cdd:cd04019    82 RAVIPLNDI 90
SH3_MPP2 cd12037
Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); ...
1136-1178 6.66e-05

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212970  Cd Length: 59  Bit Score: 42.25  E-value: 6.66e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1136 YDYAANN-----EDELSFSKGQLINVMNKDDPDWWQGEI--NGVTGLFPS 1178
Cdd:cd12037     8 YDPSSDSlipckEAGLKFRAGDLLQIVNQEDPNWWQACHveGGSAGLIPS 57
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
986-1036 6.76e-05

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212723 [Multi-domain]  Cd Length: 55  Bit Score: 41.92  E-value: 6.76e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSI---GdRSGIFPSNYVKP 1036
Cdd:cd11789     2 YRAMYDYAAADDDEVSFQEGDVIInVEIIDDGWMEGTVqrtG-QSGMLPANYVEL 55
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
349-754 6.77e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 47.75  E-value: 6.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  349 KIQEEEPQKKLPVtfeDKRKANYErgnmELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQL-ELE---K 424
Cdd:PRK03918  211 EISSELPELREEL---EKLEKEVK----ELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIeELEekvK 283
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  425 RLEKqRELERQREEERRKEIERREAAKQELE-RQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQ 503
Cdd:PRK03918  284 ELKE-LKEKAEEYIKLSEFYEEYLDELREIEkRLSRLEEEINGIEERIKELEEKEERLEELKKKLKELEKRLEELEERHE 362
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  504 QisgrLQDVRLKkqtqKTELEVLDKQC-DLEIMEIKqlqqelqeyqNKLIYLVPEKQLLNERIKNMqfsntpdsgvsllh 582
Cdd:PRK03918  363 L----YEEAKAK----KEELERLKKRLtGLTPEKLE----------KELEELEKAKEEIEEEISKI-------------- 410
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  583 kkSLEKQELCQRLKEQLDALEKETASK---------LSE------MDSYNNQLKcgnmddSVLQCLLSLLSCLNNLFLLL 647
Cdd:PRK03918  411 --TARIGELKKEIKELKKAIEELKKAKgkcpvcgreLTEehrkelLEEYTAELK------RIEKELKEIEEKERKLRKEL 482
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  648 KELRETCNTQQ--LALEQLYkikrDKLKEIErKRLELIQKKKLEdEAARKAKQGKENL---------WKENLRREEE-EK 715
Cdd:PRK03918  483 RELEKVLKKESelIKLKELA----EQLKELE-EKLKKYNLEELE-KKAEEYEKLKEKLiklkgeiksLKKELEKLEElKK 556
                         410       420       430
                  ....*....|....*....|....*....|....*....
gi 966980062  716 QKRLQEEKTQEKiqEEERKAEEKQRKDKDTLKVEEKQRE 754
Cdd:PRK03918  557 KLAELEKKLDEL--EEELAELLKELEELGFESVEELEER 593
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
1130-1181 6.96e-05

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212695 [Multi-domain]  Cd Length: 57  Bit Score: 41.97  E-value: 6.96e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1130 CQVIamYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN--GVTGLFPSNYV 1181
Cdd:cd11761     4 CKVL--YSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNksGEVGYVPENYL 55
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
763-813 7.16e-05

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212730  Cd Length: 51  Bit Score: 41.96  E-value: 7.16e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEktIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11796     3 RVLQDLSAQLDEELDLREGDVVTITG--ILDKGWFRGELNGRRGIFPEGFV 51
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
983-1035 7.26e-05

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212867 [Multi-domain]  Cd Length: 59  Bit Score: 42.29  E-value: 7.26e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  983 GEEYIALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSI---GDrSGIFPSNYVK 1035
Cdd:cd11934     2 GKRYRAVYDYNAADEDEVSFQDGDTIVnVQQIDDGWMYGTVertGD-TGMLPANYVE 57
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
1433-1540 7.28e-05

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270064  Cd Length: 100  Bit Score: 43.37  E-value: 7.28e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1433 RKLLHSG--KLYKTKSNK-ELHGFLFNDFLLLTymvKQfaVSSGSEKLfssksnaqfKMYKTPIFLNEVLVKLPTDPSSd 1509
Cdd:cd13244     1 RRLLLEGdlRLKEGKGSKvDVHCFLFTDMLLIC---KP--VKRKKDRL---------KVIRPPYLVDKLVVQELKDPGG- 65
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 966980062 1510 epvFHISHIDR------VYTLRTDNINERTAWVQKIK 1540
Cdd:cd13244    66 ---FLLVYLNEfhtavaAYTFQTSSQEDTRRWLDAIR 99
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
1134-1183 7.38e-05

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212854  Cd Length: 55  Bit Score: 41.83  E-value: 7.38e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11921     5 LKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEV 54
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
987-1035 7.38e-05

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 41.91  E-value: 7.38e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK---DGEWW-----TGSIgdrsGIFPSNYVK 1035
Cdd:cd11767     3 VALYPFTGENDEELSFEKGERLEIIEKpedDPDWWkarnaLGTT----GLVPRNYVE 55
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
1057-1113 7.55e-05

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 41.85  E-value: 7.55e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILIL-KKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd11830     1 TAKARYDFCARDMRELSLKEGDVVKIYnKKGQQGWWRGEINGR-----IGWFPSTYVE 53
MAP7 pfam05672
MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is ...
662-753 7.61e-05

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.


Pssm-ID: 461709 [Multi-domain]  Cd Length: 153  Bit Score: 44.65  E-value: 7.61e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   662 EQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRK 741
Cdd:pfam05672   33 ERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQRKAEEEAEEREQREQEEQERLQKQKEEAEAKARE 112
                           90
                   ....*....|..
gi 966980062   742 DKDTLKVEEKQR 753
Cdd:pfam05672  113 EAERQRQEREKI 124
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
762-813 7.67e-05

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212924  Cd Length: 52  Bit Score: 41.89  E-value: 7.67e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKtigEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11991     2 YVAMYTYESNEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKTGVFPSNYV 50
CALCOCO1 pfam07888
Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are ...
377-739 7.96e-05

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.


Pssm-ID: 462303 [Multi-domain]  Cd Length: 488  Bit Score: 47.20  E-value: 7.96e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   377 ELEKRRQALVEQQQREAERKaQKEKEEWERKQRELQEQEWKKQLELEKRLEKQrELERQREEERRKEIERREAAKQELER 456
Cdd:pfam07888   45 ELLQAQEAANRQREKEKERY-KRDREQWERQRRELESRVAELKEELRQSREKH-EELEEKYKELSASSEELSEEKDALLA 122
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   457 QRRLEWERIRRQEllnqknreqEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKqcdleimE 536
Cdd:pfam07888  123 QRAAHEARIRELE---------EDIKTLTQRVLERETELERMKERAKKAGAQRKEEEAERKQLQAKLQQTEE-------E 186
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   537 IKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTPdsgvslLHKKSLEKQELCQRLK---EQLDALEKETA---SKL 610
Cdd:pfam07888  187 LRSLSKEFQELRNSLAQRDTQVLQLQDTITTLTQKLTT------AHRKEAENEALLEELRslqERLNASERKVEglgEEL 260
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   611 SEMDSYNNQLKcGNMDDSVLQCLLSLLSCLNNLfLLLKELRETCNTQQLALEQLYKIKRDKL----KEIER--KRL--EL 682
Cdd:pfam07888  261 SSMAAQRDRTQ-AELHQARLQAAQLTLQLADAS-LALREGRARWAQERETLQQSAEADKDRIeklsAELQRleERLqeER 338
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062   683 IQKKKLEDEAARKakqgkenlwKENLRREEEEKQKRLQEEKTQEKI--QEEERKAEEKQ 739
Cdd:pfam07888  339 MEREKLEVELGRE---------KDCNRVQLSESRRELQELKASLRVaqKEKEQLQAEKQ 388
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
908-951 8.09e-05

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 41.91  E-value: 8.09e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 966980062  908 SWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11902     8 AYVAEREDELSLVKGSRVTVMEKcSDGWWRGSYNGQIGWFPSNYV 52
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
1057-1113 8.10e-05

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 41.93  E-value: 8.10e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1057 IAQVTSAYVASGSEQLSLAPGQLILI-LKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd11978     2 IAIARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGR-----VGWFPSTYVE 54
SH3_PACSIN_like cd11999
Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C ...
988-1034 8.18e-05

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212932 [Multi-domain]  Cd Length: 56  Bit Score: 41.85  E-value: 8.18e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGD--RSGIFPSNYV 1034
Cdd:cd11999     6 AVYDYTGQEPDELSFKAGEELLkVEDEDEQGWCKGVTDggAVGLYPANYV 55
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
764-812 8.20e-05

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 41.70  E-value: 8.20e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNY 812
Cdd:cd11817     4 ALYDFTGETEEDLSFQRGDRILVTEHLDAE--WSRGRLNGREGIFPRAF 50
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
1134-1182 8.47e-05

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 41.53  E-value: 8.47e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQ-GEINGVTGLFPSNYVK 1182
Cdd:cd11849     4 ALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLvTNHSGETGYVPANYVK 53
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
762-814 8.49e-05

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 41.60  E-value: 8.49e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGepGW-----LYGSFQgnfGWFPCNYVE 814
Cdd:cd11858     2 YKALYDFAGSVANELSLKKDDIVYIVQKEDN--GWwlakkLDESKE---GWVPAAYLE 54
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
987-1034 8.49e-05

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 41.62  E-value: 8.49e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11816     3 VARFDFEGEQEDELSFSEGDVItLKEYVGEEWAKGELNGKIGIFPLNFV 51
SH3_FCHSD1_2 cd11895
Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain ...
988-1035 8.71e-05

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212828  Cd Length: 58  Bit Score: 41.88  E-value: 8.71e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-----DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11895     4 ALYSYTGQSPEELSFPEGALIRLLPRaqdgvDDGFWRGEFGGRVGVFPSLLVE 56
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
1063-1112 8.89e-05

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 41.54  E-value: 8.89e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHV 1112
Cdd:cd11826     7 DYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGV-----TGLFPGNYV 51
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
905-952 8.98e-05

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212924  Cd Length: 52  Bit Score: 41.51  E-value: 8.98e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11991     4 AMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVR 51
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
987-1035 9.10e-05

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 41.70  E-value: 9.10e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTG--SIGdRSGIFPSNYVK 1035
Cdd:cd11962     3 VVLYDYEKDEDNEIELVEGEIVTnIEMVDEDWWMGtnSKG-ESGLFPSNYVE 53
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
1064-1114 9.15e-05

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 41.63  E-value: 9.15e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHVKL 1114
Cdd:cd11840     8 YTAQNEDELSFQKGDIINVLSKDDPDWWRGELNG-----QTGLFPSNYVEP 53
SH3_UBASH3B cd11936
Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, ...
763-815 9.46e-05

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212869  Cd Length: 62  Bit Score: 41.95  E-value: 9.46e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVD--EKTIGEPGWLYGSF--QGNFGWFPCNYVEK 815
Cdd:cd11936     5 QVIYPYTPQNDDELELVPGDYIFMSpmEQTSTSEGWIYGTSltTGCSGLLPENYITK 61
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
366-737 9.50e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 47.37  E-value: 9.50e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  366 KRKANYERGNM-----ELEKRRQALVEQQQREAERKAQKEKEEWERKQ--RELQEQEWK-----KQLELEKRLEKQRELE 433
Cdd:PRK03918  379 KRLTGLTPEKLekeleELEKAKEEIEEEISKITARIGELKKEIKELKKaiEELKKAKGKcpvcgRELTEEHRKELLEEYT 458
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  434 RQREEERRKEIERREAAKQELERQRRLEWERIRRQELLnqKNRE-QEEIVRLNSKKKSLHLE-LEALNGKHQQISGRLQD 511
Cdd:PRK03918  459 AELKRIEKELKEIEEKERKLRKELRELEKVLKKESELI--KLKElAEQLKELEEKLKKYNLEeLEKKAEEYEKLKEKLIK 536
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  512 VrlkkqtqKTELEVLDKqcdlEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQFSNTPDSGVSL-----LHKKSL 586
Cdd:PRK03918  537 L-------KGEIKSLKK----ELEKLEELKKKLAELEKKLDELEEELAELLKELEELGFESVEELEERLkelepFYNEYL 605
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  587 E----------KQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNM---DDSVLQCLLSLLSCLNNLFLLLKELRET 653
Cdd:PRK03918  606 ElkdaekelerEEKELKKLEEELDKAFEELAETEKRLEELRKELEELEKkysEEEYEELREEYLELSRELAGLRAELEEL 685
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  654 CNTQQLALEQLYKIKRDKlKEIE--RKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEE 731
Cdd:PRK03918  686 EKRREEIKKTLEKLKEEL-EEREkaKKELEKLEKALERVEELREKVKKYKALLKERALSKVGEIASEIFEELTEGKYSGV 764

                  ....*.
gi 966980062  732 ERKAEE 737
Cdd:PRK03918  765 RVKAEE 770
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
903-951 9.57e-05

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 41.57  E-value: 9.57e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11804     2 AVAKHDFKATAEDELSFKKGSILKVLnmEDDPNWYKAELDGKEGLIPKNYI 52
TOPEUc smart00435
DNA Topoisomerase I (eukaryota); DNA Topoisomerase I (eukaryota), DNA topoisomerase V, Vaccina ...
654-747 9.83e-05

DNA Topoisomerase I (eukaryota); DNA Topoisomerase I (eukaryota), DNA topoisomerase V, Vaccina virus topoisomerase, Variola virus topoisomerase, Shope fibroma virus topoisomeras


Pssm-ID: 214661 [Multi-domain]  Cd Length: 391  Bit Score: 46.57  E-value: 9.83e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062    654 CNTQQLA----LEQLYKIKrDKLKEIERKRLELiQKKKLEDEAARKAK---QGKENLWKENLRREEEEKQKRLQ-EEKTQ 725
Cdd:smart00435  265 CNHQRTVskthEKSMEKLQ-EKIKALKYQLKRL-KKMILLFEMISDLKrklKSKFERDNEKLDAEVKEKKKEKKkEEKKK 342
                            90       100
                    ....*....|....*....|....
gi 966980062    726 EKIQEEERKAE--EKQRKDKDTLK 747
Cdd:smart00435  343 KQIERLEERIEklEVQATDKEENK 366
Caldesmon pfam02029
Caldesmon;
379-752 9.88e-05

Caldesmon;


Pssm-ID: 460421 [Multi-domain]  Cd Length: 495  Bit Score: 46.78  E-value: 9.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   379 EKRRQAlveqqqREaERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIerreaAKQELERQR 458
Cdd:pfam02029   10 ERRRRA------RE-ERRRQKEEEEPSGQVTESVEPNEHNSYEEDSELKPSGQGGLDEEEAFLDRT-----AKREERRQK 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   459 RLEwERIRRQELLNQKNreQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDV------RLKKQTQKTELEVLDKQCDL 532
Cdd:pfam02029   78 RLQ-EALERQKEFDPTI--ADEKESVAERKENNEEEENSSWEKEEKRDSRLGRYkeeeteIREKEYQENKWSTEVRQAEE 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   533 EIMEIKQLQqelqeyqnKLIYLVPEKQLLNERIKNMQFSNTpdsgvslLHKKSLEKQELCQRlkeqldALEKETASKLSE 612
Cdd:pfam02029  155 EGEEEEDKS--------EEAEEVPTENFAKEEVKDEKIKKE-------KKVKYESKVFLDQK------RGHPEVKSQNGE 213
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   613 MDSYNNQLKCGNMDDSVLQCllsllsclnnlflllkELRETCNTQQLALEQ-LYKIKRdKLKEIERKRLELIQKKKLE-- 689
Cdd:pfam02029  214 EEVTKLKVTTKRRQGGLSQS----------------QEREEEAEVFLEAEQkLEELRR-RRQEKESEEFEKLRQKQQEae 276
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   690 ---DEAARKAKQGKENLWKENLRR--EEEEKQKRLQEEKTQEKIQEEERKAE--EKQRKDKDTLKVEEKQ 752
Cdd:pfam02029  277 lelEELKKKREERRKLLEEEEQRRkqEEAERKLREEEEKRRMKEEIERRRAEaaEKRQKLPEDSSSEGKK 346
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
988-1035 1.00e-04

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212930 [Multi-domain]  Cd Length: 56  Bit Score: 41.48  E-value: 1.00e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTGSI-GDRSGIFPSNYVK 1035
Cdd:cd11997     6 ALYDYTGQEADELSFKAGEELLKIGEEDEqgWCKGRLlSGRIGLYPANYVE 56
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
901-953 1.03e-04

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212879 [Multi-domain]  Cd Length: 56  Bit Score: 41.55  E-value: 1.03e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  901 LKAQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11946     1 MEAIAKYDFKATADDELSFKRGDILKVLneECDQNWYKAELNGKDGFIPKNYIEM 55
SH3_UBASH3 cd11791
Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called ...
1129-1181 1.04e-04

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212725 [Multi-domain]  Cd Length: 59  Bit Score: 41.52  E-value: 1.04e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1129 VCQVIamYDYAANNEDELSFSKGQLINVMNKD---DPDWWQGEIN---GVTGLFPSNYV 1181
Cdd:cd11791     1 VLRVL--YPYTPQEEDELELVPGDYIYVSPEEldsSSDGWVEGTSwltGCSGLLPENYT 57
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
903-947 1.05e-04

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 41.61  E-value: 1.05e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-----WWFGEVHGGRGWFP 947
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFP 51
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
985-1034 1.08e-04

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 41.36  E-value: 1.08e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11956     3 EAVACFDYTGRTAQELSFKRGDVLLLHSKaSSDWWRGEHNGMRGLIPHKYI 53
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
989-1035 1.08e-04

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 41.49  E-value: 1.08e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  989 LYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12054     6 LFEYVPQNEDELELKVGDIIDINEEVEEgWWSGTLNGKSGLFPSNFVK 53
SH3_SH3RF1_3 cd11926
Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ...
986-1036 1.15e-04

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212859 [Multi-domain]  Cd Length: 55  Bit Score: 41.49  E-value: 1.15e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGSIGDRS--GIFPSNYVKP 1036
Cdd:cd11926     2 YVAIYPYTPRKEDELELRKGEMFLVFERcqDG-WFKGTSMHTSkiGVFPGNYVAP 55
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1058-1113 1.16e-04

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 41.42  E-value: 1.16e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd12052     2 AIVEFDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGR-----RGLFPDNFVR 52
SH3_Lck cd12005
Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of ...
987-1034 1.18e-04

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212938 [Multi-domain]  Cd Length: 54  Bit Score: 41.35  E-value: 1.18e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGEWW------TGsigdRSGIFPSNYV 1034
Cdd:cd12005     3 VALYSYEPSHDGDLGFEKGEKLRILEQSGEWWkaqsltTG----QEGFIPFNFV 52
SH3_NEDD9 cd12002
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
903-954 1.18e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212935  Cd Length: 57  Bit Score: 41.51  E-value: 1.18e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKII 954
Cdd:cd12002     2 ARALYDNVPECAEELAFRKGDILTVIEQNtgglEGWWLCSLHGRQGIAPGNRLKLL 57
SH3_p47phox_1 cd12021
First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called ...
762-814 1.20e-04

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212954 [Multi-domain]  Cd Length: 53  Bit Score: 41.48  E-value: 1.20e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12021     2 YRAIADYEKSSKSEMALKTGDVVEVVEKS--ENGWWFCQLKAKRGWVPASYLE 52
SH3_Tks4_1 cd12075
First Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
1060-1110 1.21e-04

First Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the first SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213008  Cd Length: 55  Bit Score: 41.60  E-value: 1.21e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1060 VTSAYVASGSEQLSLAPGQLILILKKNTSGWWqgelqARGKKRQKGWFPAS 1110
Cdd:cd12075     5 VVANYQKQESSEISLYVGQVVDIIEKNESGWW-----FVSTADEQGWVPAT 50
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
1571-1653 1.24e-04

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 43.06  E-value: 1.24e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKAC-KPNGKSNPYCEISMGSQSYTTRTIQDTLNPKWnfNCQFFI-----KDLYQDVLCLTLFDRDQFSP 1644
Cdd:cd08688     1 LKVRVVAARDLPVMdRSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVW--NSEWFRfevddEELQDEPLQIRVMDHDTYSA 78

                  ....*....
gi 966980062 1645 DDFLGRTEI 1653
Cdd:cd08688    79 NDAIGKVYI 87
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
762-815 1.28e-04

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 41.04  E-value: 1.28e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 966980062   762 YRALYPFEARNHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGK--DNDGWWEGETGGRVGLVPSTAVEE 53
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
902-950 1.29e-04

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212712 [Multi-domain]  Cd Length: 51  Bit Score: 41.33  E-value: 1.29e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN--WWFGEVHGGRGWFPKSY 950
Cdd:cd11778     1 YVEALYDYEAQGDDEISIRVGDRIAVIRGDDGsgWTYGEINGVKGLFPTSY 51
SH3_BAIAP2L1 cd11913
Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, ...
917-952 1.32e-04

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212846  Cd Length: 58  Bit Score: 41.44  E-value: 1.32e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 966980062  917 LNFSKHDIITVL--EQQENWWFGE--VHGGRGWFPKSYVK 952
Cdd:cd11913    18 LSFAQGDVITLLipEEKDGWLYGEhdTTKARGWFPSSYTR 57
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
902-950 1.37e-04

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 41.15  E-value: 1.37e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGG---RGWFPKSY 950
Cdd:cd11821     1 RVRALYDCQADNDDELTFSEGEIIVVTgEEDDEWWEGHIEGDpsrRGVFPVSF 53
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
763-814 1.38e-04

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212827  Cd Length: 56  Bit Score: 41.08  E-value: 1.38e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQV-DEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11894     3 KALYDYEGQTDDELSFPEGAIIRIlNKENQDDDGFWEGEFNGRIGVFPSVLVE 55
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
988-1034 1.38e-04

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212837 [Multi-domain]  Cd Length: 57  Bit Score: 41.17  E-value: 1.38e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK---DGEWWT-GSIGDRSGIFPSNYV 1034
Cdd:cd11904     5 ALYPFSSSNDEELNFEKGEVMDVIEKpenDPEWWKcRKANGQVGLVPKNYV 55
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
763-816 1.40e-04

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 41.36  E-value: 1.40e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFG-WFPCNYVEKM 816
Cdd:cd11969     3 KALYDYRAKRSDELSFCKGALIHNVSKETG--GWWKGDYGGKVQhYFPSNYVEDV 55
SH3_9 pfam14604
Variant SH3 domain;
1063-1113 1.41e-04

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 41.06  E-value: 1.41e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:pfam14604    4 PYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGR-----TGLVPANYVE 49
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
986-1036 1.44e-04

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212714 [Multi-domain]  Cd Length: 55  Bit Score: 41.13  E-value: 1.44e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGSIGdRS---GIFPSNYVKP 1036
Cdd:cd11780     2 YRALYSYTPQNEDELELREGDIVYVMEKcdDG-WFVGTSE-RTglfGTFPGNYVAR 55
SH3_ARHGAP32_33 cd11835
Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; ...
1138-1181 1.48e-04

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212769 [Multi-domain]  Cd Length: 54  Bit Score: 40.90  E-value: 1.48e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062 1138 YAANNEDELSFSKGQLINVMN---KDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11835     8 YTAQAPDELSLEVGDIVSVIDmppPEESTWWRGKKGFQVGFFPSECV 54
SH3_Bem1p_1 cd11878
First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
1132-1180 1.52e-04

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212811 [Multi-domain]  Cd Length: 54  Bit Score: 41.12  E-value: 1.52e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1132 VI-AMYDYAANNEDELSFSKGQLINVMNKDDPD-WWQGE--INGVTGLFPSNY 1180
Cdd:cd11878     1 VIrALYDYRAQTPGELSFSKGDFFHVIGEEDQGeWYEATnpVTGKRGLVPKSY 53
PRK12705 PRK12705
hypothetical protein; Provisional
657-772 1.63e-04

hypothetical protein; Provisional


Pssm-ID: 237178 [Multi-domain]  Cd Length: 508  Bit Score: 46.24  E-value: 1.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  657 QQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEE-KQKRLQEEKTQEKIQE-EERK 734
Cdd:PRK12705   28 RQRLAKEAERILQEAQKEAEEKLEAALLEAKELLLRERNQQRQEARREREELQREEERlVQKEEQLDARAEKLDNlENQL 107
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 966980062  735 AEEKQRKDKDTLKVEEKQRETASVLVNYRALYPFEARN 772
Cdd:PRK12705  108 EEREKALSARELELEELEKQLDNELYRVAGLTPEQARK 145
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
764-812 1.72e-04

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 41.07  E-value: 1.72e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNY 812
Cdd:cd11952     5 ALWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNY 53
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
1058-1114 1.78e-04

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 40.80  E-value: 1.78e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNT--SGWWQGELQARgkkrqKGWFPASHVKL 1114
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKDCedKGWWKGELNGK-----RGVFPDNFVEP 55
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
1058-1114 1.80e-04

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 40.82  E-value: 1.80e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGElqargKKRQKGWFPASHVKL 1114
Cdd:cd11824     2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVE-----RNGQKGLVPGTYLEK 53
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
764-815 1.81e-04

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212695 [Multi-domain]  Cd Length: 57  Bit Score: 40.81  E-value: 1.81e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGWLYG-SFQGNFGWFPCNYVEK 815
Cdd:cd11761     6 VLYSYEAQRPDELTITEGEELEVIEDGDGD-GWVKArNKSGEVGYVPENYLQF 57
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
762-815 1.84e-04

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212767 [Multi-domain]  Cd Length: 53  Bit Score: 40.95  E-value: 1.84e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11833     2 YVALYKFKPQENEDLEMRPGDKITLLDDSNED--WWKGKIEDRVGFFPANFVQR 53
SH3_Sorbs1_1 cd11919
First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; ...
902-954 1.84e-04

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212852 [Multi-domain]  Cd Length: 55  Bit Score: 40.72  E-value: 1.84e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 954
Cdd:cd11919     2 PARAKFDFKAQTLKELPLQKGDIVYIYKQiDQNWYEGEHHGRVGIFPRSYIELL 55
SH3_Tks_3 cd12017
Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
1137-1181 1.85e-04

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212950  Cd Length: 53  Bit Score: 40.90  E-value: 1.85e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 966980062 1137 DYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd12017     7 EFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYI 51
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
1064-1115 1.85e-04

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 40.97  E-value: 1.85e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGelQARGKkrqKGWFPASHVKLL 1115
Cdd:cd12073     9 YQGEGDDEISFDPQETITDIEMVDEGWWKG--TCHGH---RGLFPANYVELL 55
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
985-1035 1.86e-04

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212881 [Multi-domain]  Cd Length: 54  Bit Score: 40.95  E-value: 1.86e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVT--QKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11948     1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIK 53
PRK00409 PRK00409
recombination and DNA strand exchange inhibitor protein; Reviewed
368-538 1.88e-04

recombination and DNA strand exchange inhibitor protein; Reviewed


Pssm-ID: 234750 [Multi-domain]  Cd Length: 782  Bit Score: 46.36  E-value: 1.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  368 KANYERGNMELEKRRQALvEQQQREAE---RKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQrelerqreeeRRKEI 444
Cdd:PRK00409  508 KKLIGEDKEKLNELIASL-EELERELEqkaEEAEALLKEAEKLKEELEEKKEKLQEEEDKLLEEA----------EKEAQ 576
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  445 ERREAAKQELERQRRlEWERIRRQELLNQKNREQEEivrlnsKKKSLHLELEALNgKHQQISGRLQD-------VRLKKQ 517
Cdd:PRK00409  577 QAIKEAKKEADEIIK-ELRQLQKGGYASVKAHELIE------ARKRLNKANEKKE-KKKKKQKEKQEelkvgdeVKYLSL 648
                         170       180
                  ....*....|....*....|....*
gi 966980062  518 TQKTE-LEVLDK---QCDLEIMEIK 538
Cdd:PRK00409  649 GQKGEvLSIPDDkeaIVQAGIMKMK 673
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
905-950 1.89e-04

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 40.82  E-value: 1.89e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQE-----NWWFGEVHGGRGWFPKSY 950
Cdd:cd11800     4 ALYTFEARSPGELSVTEGQVVTVLEKHDlkgnpEWWLVEDRGKQGYVPSNY 54
SH3_SLAP2 cd12011
Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent ...
987-1034 1.89e-04

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212944  Cd Length: 55  Bit Score: 40.88  E-value: 1.89e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGEWWT--GSIGDRSGIFPSNYV 1034
Cdd:cd12011     3 VALCNFPSGGPTELSIRMGEQLTILSEDGDWWKvsSAVTGRECYIPSNYV 52
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
984-1035 1.91e-04

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 40.79  E-value: 1.91e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  984 EEYIALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12076     1 EKYTVIYPYTARDQDEINLEKGAVVEVIQKNLEgWWKIRYQGKEGWAPASYLK 53
SH3_p47phox_2 cd12022
Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also ...
986-1035 1.95e-04

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212955 [Multi-domain]  Cd Length: 53  Bit Score: 40.59  E-value: 1.95e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12022     2 YITIKAYTAVEEDELTLLEGEAIEVIHKllDG-WWVVRKGEVTGYFPSMYLQ 52
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
763-812 1.95e-04

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 40.76  E-value: 1.95e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQG---NFGWFPCNY 812
Cdd:cd11821     3 RALYDCQADNDDELTFSEGEIIVVTGE--EDDEWWEGHIEGdpsRRGVFPVSF 53
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
764-814 2.02e-04

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 40.56  E-value: 2.02e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12046     4 ALFSYEASQPEDLEFQKGDVILVLSKVNED--WLEGQCKGKIGIFPSAFVE 52
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
988-1034 2.02e-04

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 40.57  E-value: 2.02e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSvEPGD--LTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11829     4 TLYAFTG-EQHQqgLSFEAGELIRVLQApDGGWWEGEKDGLRGWFPASYV 52
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
762-813 2.10e-04

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212717 [Multi-domain]  Cd Length: 55  Bit Score: 40.84  E-value: 2.10e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYV 813
Cdd:cd11783     2 YVALYPYKPQKPDELELRKGEMYTVTEKC--QDGWFKGTslRTGQSGVFPGNYV 53
SH3_ARHGEF16_26 cd11938
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ...
1059-1113 2.15e-04

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212871  Cd Length: 55  Bit Score: 40.60  E-value: 2.15e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1059 QVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGElqaRGKKRQKGWFPASHVK 1113
Cdd:cd11938     3 EIIKAYTAKQPDELSLQQADVVLVLQTESDGWYYGE---RLRDGERGWFPSSCAK 54
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
1571-1683 2.16e-04

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 42.64  E-value: 2.16e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1571 LMVHVIEATELKackPNGKSNPYCEISMGS-QSYTTRTIQDtLNPKWNFncQFFIKDLYQDV----LCLTLFDRDQFSPD 1645
Cdd:cd08383     2 LRLRILEAKNLP---SKGTRDPYCTVSLDQvEVARTKTVEK-LNPFWGE--EFVFDDPPPDVtfftLSFYNKDKRSKDRD 75
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 966980062 1646 DFLGRTEipvakIRTEQESKGPVTRRLLLHEVPTGEVW 1683
Cdd:cd08383    76 IVIGKVA-----LSKLDLGQGKDEWFPLTPVDPDSEVQ 108
SH3_MYO15B cd12068
Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its ...
764-814 2.16e-04

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 213001  Cd Length: 55  Bit Score: 40.63  E-value: 2.16e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd12068     4 ALRSYITDDKSLLSFHRGDLIKLLPMAGLEPGWQFGSTGGRSGLFPADIVQ 54
DUF4659 pfam15558
Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins ...
372-495 2.22e-04

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.


Pssm-ID: 464768 [Multi-domain]  Cd Length: 374  Bit Score: 45.41  E-value: 2.22e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   372 ERGNMELEKRRQALVEQQQREAERKAQK--EKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREA 449
Cdd:pfam15558   61 EQWQAEKEQRKARLGREERRRADRREKQviEKESRWREQAEDQENQRQEKLERARQEAEQRKQCQEQRLKEKEEELQALR 140
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 966980062   450 AKQELERQRRLEWERIRRQellnQKNREQEEIVRLNSKKKSLHLEL 495
Cdd:pfam15558  141 EQNSLQLQERLEEACHKRQ----LKEREEQKKVQENNLSELLNHQA 182
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
902-953 2.26e-04

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 40.39  E-value: 2.26e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11874     1 RCKVLFSYTPQNEDELELKVGDTIEVLGEvEEGWWEGKLNGKVGVFPSNFVKE 53
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
901-953 2.26e-04

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 40.59  E-value: 2.26e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  901 LKAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11956     2 VEAVACFDYTGRTAQELSFKRGDVLLLHSKaSSDWWRGEHNGMRGLIPHKYISV 55
DDRGK pfam09756
DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and ...
671-750 2.32e-04

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.


Pssm-ID: 370664 [Multi-domain]  Cd Length: 188  Bit Score: 43.88  E-value: 2.32e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   671 KLKEIERKRLELIQKKKLEDEAA-------RKAKQGKENLWKEnlRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDK 743
Cdd:pfam09756    2 KLGAKKRAKLELKEAKRQQREAEeeereerEKLEEKREEEYKE--REEREEEAEKEKEEEERKQEEEQERKEQEEYEKLK 79

                   ....*..
gi 966980062   744 DTLKVEE 750
Cdd:pfam09756   80 SQFVVEE 86
SH3_SNX18 cd11897
Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal ...
1134-1183 2.48e-04

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212830 [Multi-domain]  Cd Length: 55  Bit Score: 40.36  E-value: 2.48e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEIN--GVTGLFPSNYVKM 1183
Cdd:cd11897     4 ALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNsrGDRGLFPASYVEV 55
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
1064-1114 2.48e-04

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 40.45  E-value: 2.48e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWqgeLQARGKKRQKGWFPASHVKL 1114
Cdd:cd11858     8 FAGSVANELSLKKDDIVYIVQKEDNGWW---LAKKLDESKEGWVPAAYLEE 55
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
909-952 2.49e-04

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 40.26  E-value: 2.49e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 966980062  909 WTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 952
Cdd:cd12052     8 YKAQHEDELTITVGDIITKIKKDDGgWWEGEIKGRRGLFPDNFVR 52
tolA_full TIGR02794
TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the ...
662-754 2.51e-04

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]


Pssm-ID: 274303 [Multi-domain]  Cd Length: 346  Bit Score: 45.22  E-value: 2.51e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   662 EQLYKIKRDKLKEIERKRLELIQKKKLED-----------EAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQE 730
Cdd:TIGR02794   68 ERQKKLEQQAEEAEKQRAAEQARQKELEQraaaekaakqaEQAAKQAEEKQKQAEEAKAKQAAEAKAKAEAEAERKAKEE 147
                           90       100
                   ....*....|....*....|....
gi 966980062   731 EERKAEEKqRKDKDTLKVEEKQRE 754
Cdd:TIGR02794  148 AAKQAEEE-AKAKAAAEAKKKAEE 170
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
987-1035 2.54e-04

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212904 [Multi-domain]  Cd Length: 59  Bit Score: 40.77  E-value: 2.54e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11971     3 VAIYDYSKDKDDELSFMEGAIIYVIKKnDDGWYEGVCNGVTGLFPGNYVE 52
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
905-952 2.58e-04

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 40.56  E-value: 2.58e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd12046     4 ALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVE 52
CCDC47 pfam07946
PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of ...
364-429 2.59e-04

PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins. CCDC47 is required to maintain the stability of Asterix. CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis. It is also involved in the regulation of calcium ion homeostasis in the ER, being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway.


Pssm-ID: 462322  Cd Length: 323  Bit Score: 45.25  E-value: 2.59e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   364 EDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKrlEKQ 429
Cdd:pfam07946  257 EALKKAKKTREEEIEKIKKAAEEERAEEAQEKKEEAKKKEREEKLAKLSPEEQRKYEEKER--KKE 320
SH3_ARHGEF9 cd11975
Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also ...
901-953 2.74e-04

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212908  Cd Length: 62  Bit Score: 40.46  E-value: 2.74e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  901 LKAQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11975     5 VSAEAVWDHVTMANRELAFKAGDVIKVLDaSNKDWWWGQIDDEEGWFPASFVRL 58
SH3_PACSIN1-2 cd11998
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) ...
988-1036 2.75e-04

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212931 [Multi-domain]  Cd Length: 56  Bit Score: 40.32  E-value: 2.75e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTGSI-GDRSGIFPSNYVKP 1036
Cdd:cd11998     5 ALYDYDGQEQDELSFKAGDELTKLEDEDEqgWCKGRLdSGQVGLYPANYVEP 56
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
987-1035 2.78e-04

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 40.09  E-value: 2.78e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11959     3 VALYDYQAADDDEISFDPDDIITnIEMIDEGWWRGVCRGKYGLFPANYVE 52
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
1059-1114 2.79e-04

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 40.43  E-value: 2.79e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062 1059 QVTSAYV--ASGSEQLSLAPGQLILILKKNTSgWWQGELQargkKRQKGWFPASHVKL 1114
Cdd:cd11837     1 TATALYPwrAKKENHLSFAKGDIITVLEQQEM-WWFGELE----GGEEGWFPKSYVKE 53
SH3_Tks_2 cd12016
Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
1131-1182 2.83e-04

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212949  Cd Length: 54  Bit Score: 40.13  E-value: 2.83e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12016     2 KYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLK 53
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
987-1035 2.88e-04

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 40.31  E-value: 2.88e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIYNKKGQqgWWRGEINGRIGWFPSTYVE 53
SH3_Shank1 cd11982
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also ...
986-1034 2.95e-04

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212915 [Multi-domain]  Cd Length: 52  Bit Score: 40.38  E-value: 2.95e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILV-TQKDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11982     3 FMAVKPYQSQAEGEISLSKGEKIKVlSVGEGGFWEGQVKGRVGWFPSDCV 52
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
983-1035 2.96e-04

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 40.36  E-value: 2.96e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  983 GEEYIALYPYSSVEPGDLTFTEGEEILVTQ--KDGEWWTGSIGD-RSGIFPSNYVK 1035
Cdd:cd11769     1 GTECIAKYNFNGASEEDLPFKKGDILTIVAvtKDPNWYKAKNKDgREGMIPANYVQ 56
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
905-951 2.98e-04

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 40.36  E-value: 2.98e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 951
Cdd:cd11772     4 ALYDYEAQHPDELSFEEGDLLYISDKSDpNWWKATCGGKTGLIPSNYV 51
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
1067-1113 3.04e-04

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 40.44  E-value: 3.04e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062 1067 SGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd12061    11 TNEDELSFSKGDVIHVTRVEEGGWWEGTHNGR-----TGWFPSNYVR 52
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
249-307 3.09e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 42.47  E-value: 3.09e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062  249 RQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMH 307
Cdd:COG5126    72 RAAFDLLDTDGDGKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAVR 130
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
986-1033 3.12e-04

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 40.10  E-value: 3.12e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRS-------GIFPSNY 1033
Cdd:cd11773     2 YKALYDYEPQTEDELTIQEDDILYLLEKsDDDWWKVKLKVNSsdddepvGLVPATY 57
SH3_BOI cd11886
Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces ...
1132-1180 3.13e-04

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212819  Cd Length: 55  Bit Score: 40.01  E-value: 3.13e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDD---PDWWQGE--INGVTGLFPSNY 1180
Cdd:cd11886     2 LIVIHDFNARSEDELTLKPGDKIELIEDDEefgDGWYLGRnlRTGETGLFPVVF 55
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
905-951 3.16e-04

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212767 [Multi-domain]  Cd Length: 53  Bit Score: 40.18  E-value: 3.16e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11833     4 ALYKFKPQENEDLEMRPGDKITLLDdSNEDWWKGKIEDRVGFFPANFV 51
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
335-755 3.24e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 45.82  E-value: 3.24e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   335 KQIDSINGTLPSY-QKIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKE---------KEEW 404
Cdd:TIGR02168  281 EEIEELQKELYALaNEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDELAEELAELEEKLEelkeeleslEAEL 360
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   405 ERKQRELQEQEwKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELER-QRRLEWERIRRQELL-----NQKNREQ 478
Cdd:TIGR02168  361 EELEAELEELE-SRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERlEDRRERLQQEIEELLkkleeAELKELQ 439
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   479 EEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCD-LEIM--EIKQLQQELQEYQNKLIYLV 555
Cdd:TIGR02168  440 AELEELEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQARLDsLERLqeNLEGFSEGVKALLKNQSGLS 519
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   556 PEKQLLNERIK---------------NMQF-----SNTPDSGVSLLHKKSLEKQELC----------QRLKEQLDALEKE 605
Cdd:TIGR02168  520 GILGVLSELISvdegyeaaieaalggRLQAvvvenLNAAKKAIAFLKQNELGRVTFLpldsikgteiQGNDREILKNIEG 599
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   606 TASKLSEMDSYNNQLK--CGNMDDSV-----LQCLLSLLSCLNNLFLL-------------------------------L 647
Cdd:TIGR02168  600 FLGVAKDLVKFDPKLRkaLSYLLGGVlvvddLDNALELAKKLRPGYRIvtldgdlvrpggvitggsaktnssilerrreI 679
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   648 KELRETCNTQQLALEQLyKIKRDKL-KEIERKRLELIQKKKLEDEAARKAKQGKENLwkENLRREEEEKQKRL-QEEKTQ 725
Cdd:TIGR02168  680 EELEEKIEELEEKIAEL-EKALAELrKELEELEEELEQLRKELEELSRQISALRKDL--ARLEAEVEQLEERIaQLSKEL 756
                          490       500       510
                   ....*....|....*....|....*....|
gi 966980062   726 EKIQEEERKAEEKQRKDKDTLKVEEKQRET 755
Cdd:TIGR02168  757 TELEAEIEELEERLEEAEEELAEAEAEIEE 786
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
762-813 3.39e-04

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 40.40  E-value: 3.39e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGWLYGSFQ-GNFGWFPCNYV 813
Cdd:cd12007     3 FVALYDYEARTTEDLSFKKGERFQIINNTEGD-WWEARSIAtGKNGYIPSNYV 54
SH3_Brk cd11847
Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called ...
1133-1181 3.56e-04

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212781 [Multi-domain]  Cd Length: 58  Bit Score: 40.23  E-value: 3.56e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDpDWWQ----GEINGVT--GLFPSNYV 1181
Cdd:cd11847     3 KALWDFKARGDEELSFQAGDQFRIAERSG-DWWTalklDRAGGVVaqGFVPNNYL 56
SH3_RUSC1 cd11958
Src homology 3 domain of RUN and SH3 domain-containing protein 1; RUSC1, also called NESCA ...
1132-1180 3.56e-04

Src homology 3 domain of RUN and SH3 domain-containing protein 1; RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212891 [Multi-domain]  Cd Length: 51  Bit Score: 39.82  E-value: 3.56e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1132 VIAMYDYAANnEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11958     2 VRALCDHAGS-ESQLSFRKGEELQVLGTVDEDWIRCRRGDREGLVPVGY 49
SH3_CRK_C cd11759
C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
1055-1114 3.60e-04

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212693 [Multi-domain]  Cd Length: 57  Bit Score: 40.16  E-value: 3.60e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1055 PEIAQVTSAYV--ASGSEQLSLAPGQLILILKKNTSGWWQGELqaRGKkrqKGWFPASHVKL 1114
Cdd:cd11759     1 PAYARVIQKRVpnAYDKTALALEVGDLVKVTKINVSGQWEGEL--NGK---VGHFPFTHVEL 57
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
1064-1114 3.70e-04

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212805 [Multi-domain]  Cd Length: 56  Bit Score: 39.87  E-value: 3.70e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNtSGWWQGELQarGKKRQKGWFPASHVKL 1114
Cdd:cd11872     8 FQGDGEHQLSLQVGDTVQILEEC-EGWYRGFSL--RNKSLKGIFPKSYVHI 55
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
763-814 3.78e-04

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212862  Cd Length: 54  Bit Score: 39.92  E-value: 3.78e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11929     4 KALCNYRGHNPGDLKFNKGDVIllrrQLDEN------WYLGEINGVSGIFPASSVE 53
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
1576-1662 3.80e-04

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 41.78  E-value: 3.80e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1576 IEATELKACKPNGKSNPYCEISMGSQS------YTTRTIQDTLNPKWN-FNCQFFikDL----YQDVLCLTLFDRDQFSP 1644
Cdd:cd04047     7 FSGKKLDKKDFFGKSDPFLEISRQSEDgtwvlvYRTEVIKNTLNPVWKpFTIPLQ--KLcngdYDRPIKIEVYDYDSSGK 84
                          90
                  ....*....|....*...
gi 966980062 1645 DDFLGRTEIPVAKIRTEQ 1662
Cdd:cd04047    85 HDLIGEFETTLDELLKSS 102
PRK12704 PRK12704
phosphodiesterase; Provisional
666-772 3.87e-04

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 45.15  E-value: 3.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  666 KIKRDKLKEIERKRLELIQKKKLEDEAARKAK--QGKENLWKE--------NLRREE-EEKQKRLQE------------E 722
Cdd:PRK12704   27 KIAEAKIKEAEEEAKRILEEAKKEAEAIKKEAllEAKEEIHKLrnefekelRERRNElQKLEKRLLQkeenldrklellE 106
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  723 KTQEKIQEEERKAEEKQRK-DKDTLKVEEKQRETASVLVNYRALYPFEARN 772
Cdd:PRK12704  107 KREEELEKKEKELEQKQQElEKKEEELEELIEEQLQELERISGLTAEEAKE 157
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
764-816 3.87e-04

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212904 [Multi-domain]  Cd Length: 59  Bit Score: 40.00  E-value: 3.87e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd11971     4 AIYDYSKDKDDELSFMEGAIIYVIKKN--DDGWYEGVCNGVTGLFPGNYVESI 54
SH3_Intersectin2_4 cd11994
Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
903-954 3.88e-04

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212927  Cd Length: 59  Bit Score: 39.91  E-value: 3.88e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHG-----GRGWFPKSYVKII 954
Cdd:cd11994     2 AQVTTAYVASGVEQLSLSPGQLILILKKNSSgWWLGELQArgkkrQKGWFPASHVKLL 59
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
988-1035 4.00e-04

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 39.99  E-value: 4.00e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11920     5 AVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYVE 53
SH3_UBASH3A cd11937
Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is ...
763-815 4.02e-04

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212870 [Multi-domain]  Cd Length: 60  Bit Score: 40.00  E-value: 4.02e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVD--EKTIGEPGWLYGSFQ--GNFGWFPCNYVEK 815
Cdd:cd11937     4 RALFQYKPQNIDELMLSPGDYIFVDptQQSEASEGWVIGISHrtGCRGFLPENYTER 60
SH3_DNMBP_C2 cd12141
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
905-952 4.23e-04

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213017 [Multi-domain]  Cd Length: 57  Bit Score: 39.79  E-value: 4.23e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQE-----NWWFGEVHGGRGWFPKSYVK 952
Cdd:cd12141     4 AVYTFKARSPNELSVSANQRVRILEFSDltgnkEWWLAEANGQKGYVPSNYIR 56
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
1070-1113 4.30e-04

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 39.99  E-value: 4.30e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 966980062 1070 EQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd12060    16 DELSVCKGDIIYVTRVEEGGWWEGTLNGK-----TGWFPSNYVR 54
Myosin_tail_1 pfam01576
Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and ...
379-754 4.33e-04

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.


Pssm-ID: 460256 [Multi-domain]  Cd Length: 1081  Bit Score: 45.17  E-value: 4.33e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   379 EKRRQALVEQQQREAERKAQKEKE--EWERKQRELQEQewkkqlelEKRLEKQRELERQREEERRKEIERREAAKQELER 456
Cdd:pfam01576    4 EEEMQAKEEELQKVKERQQKAESElkELEKKHQQLCEE--------KNALQEQLQAETELCAEAEEMRARLAARKQELEE 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   457 -----QRRLEWERIRRQELLNQKNREQEEIVRLNSkkkslHLELEalngkhqqisgrlQDVRLKKQTQKTELEVLDKQCD 531
Cdd:pfam01576   76 ilhelESRLEEEEERSQQLQNEKKKMQQHIQDLEE-----QLDEE-------------EAARQKLQLEKVTTEAKIKKLE 137
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   532 LEIMEIKqlqqelqEYQNKLIylvPEKQLLNERIKNMQFSNTPDSGVSLLHKKSLEKQE-----LCQRL-KEQLDALEKE 605
Cdd:pfam01576  138 EDILLLE-------DQNSKLS---KERKLLEERISEFTSNLAEEEEKAKSLSKLKNKHEamisdLEERLkKEEKGRQELE 207
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   606 TASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRETCNTQQLALEqlykikrdKLKEIERKRLELIQK 685
Cdd:pfam01576  208 KAKRKLEGESTDLQEQIAELQAQIAELRAQLAKKEEELQAALARLEEETAQKNNALK--------KIRELEAQISELQED 279
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   686 KKLEDEAARKAKQGKENLWKE--NLRRE-----------EEEKQKRLQEEKTQEKIQEEERKAEEKQRKD---KDTLKVE 749
Cdd:pfam01576  280 LESERAARNKAEKQRRDLGEEleALKTEledtldttaaqQELRSKREQEVTELKKALEEETRSHEAQLQEmrqKHTQALE 359

                   ....*
gi 966980062   750 EKQRE 754
Cdd:pfam01576  360 ELTEQ 364
SH3_ARHGEF5_19 cd11940
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ...
1059-1114 4.43e-04

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212873  Cd Length: 55  Bit Score: 39.78  E-value: 4.43e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062 1059 QVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGelqARGKKRQKGWFPASHVKL 1114
Cdd:cd11940     3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEG---VRLSDGERGWFPQSHVEE 55
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
905-950 4.65e-04

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 39.91  E-value: 4.65e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLE---QQENWWFGEVHGGRGWFPKSY 950
Cdd:cd11952     5 ALWDYSAEFPDELSFKEGDMVTVLRkdgEGTDWWWASLCGREGYVPRNY 53
SH3_Nck2_3 cd11903
Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
763-813 4.74e-04

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212836 [Multi-domain]  Cd Length: 59  Bit Score: 40.04  E-value: 4.74e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLY-GSFQGNFGWFPCNYV 813
Cdd:cd11903     4 QTLYPFSSVTEEELNFEKGETMEVIEKPENDPEWWKcKNSRGQVGLVPKNYV 55
SH3_Shank1 cd11982
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also ...
761-813 4.83e-04

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212915 [Multi-domain]  Cd Length: 52  Bit Score: 39.61  E-value: 4.83e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  761 NYRALYPFEARNHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11982     2 TFMAVKPYQSQAEGEISLSKGEKIKV--LSVGEGGFWEGQVKGRVGWFPSDCV 52
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
1575-1656 4.94e-04

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 41.83  E-value: 4.94e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1575 VIEATELKACKPNGKSNPYCEISM-GSQSYTTRTiqDTL---NPKWNFNCQFFIKD--LYQDVLCLT--LFDRDQFSPDD 1646
Cdd:cd04051     6 IISAEDLKNVNLFGKMKVYAVVWIdPSHKQSTPV--DRDggtNPTWNETLRFPLDErlLQQGRLALTieVYCERPSLGDK 83
                          90
                  ....*....|
gi 966980062 1647 FLGRTEIPVA 1656
Cdd:cd04051    84 LIGEVRVPLK 93
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
1064-1112 5.03e-04

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 39.80  E-value: 5.03e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTS-----GWWQGELQARgkkrqKGWFPASHV 1112
Cdd:cd11876     8 YDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDK-----VGIFPSNYV 56
SH3_EFS cd12003
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
903-955 5.06e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212936  Cd Length: 62  Bit Score: 39.87  E-value: 5.06e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQE----NWWFGEVHGGRGWFPKSYVKIIP 955
Cdd:cd12003     3 AKALYDNAAESPEELSFRRGDVLMVLKREHgslpGWWLCSLHGQQGIAPANRLRLLP 59
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
1569-1654 5.17e-04

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 42.02  E-value: 5.17e-04
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gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGS-----QSYTTRTIQDTLNPKWNfncQFFIKDLYQDVL-----CLTLFD 1638
Cdd:cd08405    15 NRITVNIIKARNLKAMDINGTSDPYVKVWLMYkdkrvEKKKTVIKKRTLNPVFN---ESFIFNIPLERLrettlIITVMD 91
                          90
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gi 966980062 1639 RDQFSPDDFLGRTEIP 1654
Cdd:cd08405    92 KDRLSRNDLIGKIYLG 107
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
1058-1114 5.31e-04

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 39.62  E-value: 5.31e-04
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gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWqgelqaRGKKRQK-GWFPASHVKL 1114
Cdd:cd11874     2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWW------EGKLNGKvGVFPSNFVKE 53
SH3_Endophilin_B cd11802
Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, ...
902-950 5.45e-04

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212736 [Multi-domain]  Cd Length: 52  Bit Score: 39.58  E-value: 5.45e-04
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLE---QQENWWFGEVHGGRGWFPKSY 950
Cdd:cd11802     1 KARVLYDYDAEDSTELSLLADEVITVYElpgMDEDYMMGERGSQRGKVPVAY 52
SH3_ephexin1 cd11939
Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called ...
765-815 5.51e-04

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212872 [Multi-domain]  Cd Length: 55  Bit Score: 39.54  E-value: 5.51e-04
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gi 966980062  765 LYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYVEK 815
Cdd:cd11939     5 VHPYVSQEPDELSLELADVLNILDKT--DDGWIFGErlHDQERGWFPSSVVEE 55
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
997-1034 5.54e-04

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212730  Cd Length: 51  Bit Score: 39.26  E-value: 5.54e-04
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gi 966980062  997 PGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11796    13 DEELDLREGDVVTITGiLDKGWFRGELNGRRGIFPEGFV 51
SH3_SH3TC cd11885
Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins ...
988-1034 5.55e-04

Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins and similar domains; This subfamily is composed of vertebrate SH3TC proteins and hypothetical fungal proteins containing BAR and SH3 domains. Mammals contain two SH3TC proteins, SH3TC1 and SH3TC2. The function of SH3TC1 is unknown. SH3TC2 is localized in Schwann cells in the peripheral nervous system, where it interacts with Rab11 and plays a role in peripheral nerve myelination. Mutations in SH3TC2 are associated with Charcot-Marie-Tooth disease type 4C, a severe hereditary peripheral neuropathy with symptoms that include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212818  Cd Length: 55  Bit Score: 39.61  E-value: 5.55e-04
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVT---QKDGEWWTGSIGD--RSGIFPSNYV 1034
Cdd:cd11885     4 AKMDFEGVEPGELSFRQGDSIEIIgdlIPGLQWFVGRSKSsgRVGFVPTNHF 55
SH3_Tks_1 cd12015
First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
897-950 5.58e-04

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212948  Cd Length: 53  Bit Score: 39.33  E-value: 5.58e-04
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gi 966980062  897 VVENLKAQalcswtakKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSY 950
Cdd:cd12015     4 VVADYKKQ--------QPNEISLRAGDVVDVIEKNENgWWFVSLEDEQGWVPATY 50
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
762-813 5.58e-04

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 39.65  E-value: 5.58e-04
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gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGWLYGSF-QGNFGWFPCNYV 813
Cdd:cd12006     3 FVALYDYEARTEDDLSFHKGEKFQILNSSEGD-WWEARSLtTGETGYIPSNYV 54
SH3_NEDD9 cd12002
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
1134-1183 5.59e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212935  Cd Length: 57  Bit Score: 39.58  E-value: 5.59e-04
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gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDD---PDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd12002     4 ALYDNVPECAEELAFRKGDILTVIEQNTgglEGWWLCSLHGRQGIAPGNRLKL 56
SH3_SNX18 cd11897
Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal ...
988-1035 5.61e-04

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212830 [Multi-domain]  Cd Length: 55  Bit Score: 39.59  E-value: 5.61e-04
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWW---TGSIGDRsGIFPSNYVK 1035
Cdd:cd11897     4 ALYDFRSENPGEISLREHEVLsLCSEQDIEGWlegVNSRGDR-GLFPASYVE 54
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
762-813 5.69e-04

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 39.30  E-value: 5.69e-04
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gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYV 813
Cdd:cd11806     2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVD--WWWAEHNGCCGYIPASHL 51
SH3_Shank3 cd11984
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also ...
986-1034 5.95e-04

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212917  Cd Length: 52  Bit Score: 39.16  E-value: 5.95e-04
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11984     3 FIAVKAYSPQGEGEIQLNRGERVKVLSiGEGGFWEGTVKGRTGWFPADCV 52
SH3_Tks5_2 cd12077
Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
1063-1113 5.98e-04

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213010  Cd Length: 54  Bit Score: 39.24  E-value: 5.98e-04
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gi 966980062 1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQgeLQARGKkrqKGWFPASHVK 1113
Cdd:cd12077     8 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWY--IRYLGK---EGWAPASYLK 53
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1065-1110 5.99e-04

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 39.22  E-value: 5.99e-04
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gi 966980062 1065 VASGSEQLSLAPGQLILILKKNTSGWWQGELQarGKKRQKGWFPAS 1110
Cdd:cd11821     9 QADNDDELTFSEGEIIVVTGEEDDEWWEGHIE--GDPSRRGVFPVS 52
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
1562-1656 6.00e-04

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 41.47  E-value: 6.00e-04
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gi 966980062 1562 SQKTSGigrLMVHVIEATELKACKP-NGKSNPYCEI------SMGSQSyTTRTIQDTLNPKWNFNCQFFIK--DLYQDVL 1632
Cdd:cd08521    10 NYKTGS---LEVHIKECRNLAYADEkKKRSNPYVKVyllpdkSKQSKR-KTSVKKNTTNPVFNETLKYHISksQLETRTL 85
                          90       100
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gi 966980062 1633 CLTLFDRDQFSPDDFLGRTEIPVA 1656
Cdd:cd08521    86 QLSVWHHDRFGRNTFLGEVEIPLD 109
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
903-952 6.09e-04

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 39.62  E-value: 6.09e-04
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gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQ--ENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11978     3 AIARYDFCARDMRELSLLKGDVVKIYTKMstNGWWRGEVNGRVGWFPSTYVE 54
SH3_Tks_3 cd12017
Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
762-815 6.13e-04

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212950  Cd Length: 53  Bit Score: 39.36  E-value: 6.13e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12017     2 YFTIGEFQATIQDGISFQKGQKVEVIDKNPS--GWWYVKIDGKEGWAPSSYIEK 53
SH3_Tks_2 cd12016
Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
1060-1113 6.15e-04

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212949  Cd Length: 54  Bit Score: 39.36  E-value: 6.15e-04
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                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1060 VTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd12016     5 TTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGK-----EGWAPATYLK 53
SH3_SH3RF_2 cd11787
Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
987-1033 6.15e-04

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212721 [Multi-domain]  Cd Length: 53  Bit Score: 39.24  E-value: 6.15e-04
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                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  987 IALYPYssvEPGD------LTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNY 1033
Cdd:cd11787     3 KALYDF---EMKDedekdcLTFKKGDVITVIRRvDENWAEGRLGDKIGIFPISF 53
SH3_Irsp53 cd11915
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known ...
902-954 6.18e-04

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212848  Cd Length: 59  Bit Score: 39.61  E-value: 6.18e-04
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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062  902 KAQALCSWTAKkDNH--LNFSKHDIITVL--EQQENWWFGEVHGG--RGWFPKSYVKII 954
Cdd:cd11915     2 RVQAIFSHAAG-DNStlLSFKEGDYITLLvpEARDGWHYGECEKTkmRGWFPFSYTRVL 59
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
986-1036 6.19e-04

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 39.29  E-value: 6.19e-04
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gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRS--GIFPSNYVKP 1036
Cdd:cd11858     2 YKALYDFAGSVANELSLKKDDIVYIVQKeDNGWWLAKKLDESkeGWVPAAYLEE 55
SH3_Tks5_2 cd12077
Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
1133-1182 6.28e-04

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213010  Cd Length: 54  Bit Score: 39.24  E-value: 6.28e-04
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                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12077     4 VTVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 53
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
988-1035 6.52e-04

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212907  Cd Length: 54  Bit Score: 39.28  E-value: 6.52e-04
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gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11974     5 ALWDHVTMDDQELAFKAGDVIRVLEaSNKDWWWGRNEDREAWFPASFVR 53
SH3_CIP4-like cd11911
Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of ...
1131-1183 6.56e-04

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212844 [Multi-domain]  Cd Length: 55  Bit Score: 39.17  E-value: 6.56e-04
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQG--EINGVTGLFPSNYVKM 1183
Cdd:cd11911     1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWTRvrKNNGDEGYVPTSYIEV 55
SH3_MYO15B cd12068
Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its ...
1132-1182 6.71e-04

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 213001  Cd Length: 55  Bit Score: 39.47  E-value: 6.71e-04
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gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINV--MNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12068     2 VVALRSYITDDKSLLSFHRGDLIKLlpMAGLEPGWQFGSTGGRSGLFPADIVQ 54
SH3_RUSC2 cd11957
Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or ...
1131-1181 6.87e-04

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212890  Cd Length: 52  Bit Score: 39.13  E-value: 6.87e-04
                          10        20        30        40        50
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gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11957     1 EVKALCHHIATEPGQLSFNKGDILQVLSRADGDWLRCSLGPDSGLVPIAYV 51
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
902-952 6.99e-04

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 39.21  E-value: 6.99e-04
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gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd12055     1 RCQVAFSYLPQNEDELELKVGDIIEVVgEVEEGWWEGVLNGKTGMFPSNFIK 52
CCDC34 pfam13904
Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several ...
670-773 7.02e-04

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.


Pssm-ID: 464032 [Multi-domain]  Cd Length: 221  Bit Score: 43.15  E-value: 7.02e-04
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gi 966980062   670 DKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEE-ERKAEEKQRKDKDTLKV 748
Cdd:pfam13904   39 TYARKLEGLKLERQPLEAYENWLAAKQRQRQKELQAQKEEREKEEQEAELRKRLAKEKYQEWlQRKARQQTKKREESHKQ 118
                           90       100
                   ....*....|....*....|....*
gi 966980062   749 EEKQRETASVLVNYRALYPFEARNH 773
Cdd:pfam13904  119 KAAESASKSLAKPERKVSQEEAKEV 143
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
904-951 7.07e-04

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 38.95  E-value: 7.07e-04
                          10        20        30        40        50
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gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 951
Cdd:cd11866     3 MGLWDCSGNEPDELSFKRGDLIYIISKEYDsfgWWVGELNGKVGLVPKDYL 53
SH3_p47phox_2 cd12022
Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also ...
1133-1182 7.14e-04

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212955 [Multi-domain]  Cd Length: 53  Bit Score: 39.05  E-value: 7.14e-04
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gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYVK 1182
Cdd:cd12022     3 ITIKAYTAVEEDELTLLEGEAIEVIHKLLDGWWVVRKGEVTGYFPSMYLQ 52
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
903-953 7.20e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212778  Cd Length: 56  Bit Score: 39.25  E-value: 7.20e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd11844     2 ARALYDNVAESPDELAFRRGDILTVLEQNtaglEGWWLCSLRGRQGIAPGNRLKL 56
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
1064-1112 7.22e-04

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 39.36  E-value: 7.22e-04
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                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTS-----GWWQGELQARgkkrqKGWFPASHV 1112
Cdd:cd12059     8 YEASAEDELTLRRGDRVEVLSKDSAvsgdeGWWTGKINDR-----VGIFPSNYV 56
SH3_ASPP1 cd11954
Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates ...
988-1032 7.26e-04

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212887 [Multi-domain]  Cd Length: 57  Bit Score: 39.23  E-value: 7.26e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQK----DGEWWTGSIGDRSGIFPSN 1032
Cdd:cd11954     5 ALWDYEAQNADELSFQEGDAITILRRkddsETEWWWARLNDKEGYVPKN 53
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
1064-1114 7.70e-04

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212907  Cd Length: 54  Bit Score: 39.28  E-value: 7.70e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGelqaRGKKRQkGWFPASHVKL 1114
Cdd:cd11974     9 HVTMDDQELAFKAGDVIRVLEASNKDWWWG----RNEDRE-AWFPASFVRL 54
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
652-726 7.78e-04

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 44.34  E-value: 7.78e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  652 ETCNTQQLALE-------QLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKT 724
Cdd:PTZ00266  441 EKENAHRKALEmkilekkRIERLEREERERLERERMERIERERLERERLERERLERDRLERDRLDRLERERVDRLERDRL 520

                  ..
gi 966980062  725 QE 726
Cdd:PTZ00266  521 EK 522
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
763-815 7.96e-04

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 38.88  E-value: 7.96e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd11758     4 RALFDFPGNDDEDLPFKKGEILTVIRKP-EEQWWNARNSEGKTGMIPVPYVEK 55
SH3_RUSC1_like cd11810
Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that ...
1132-1180 7.99e-04

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212744  Cd Length: 50  Bit Score: 38.96  E-value: 7.99e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11810     2 VRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50
SH3_CASK cd12081
Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a ...
1132-1178 8.04e-04

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213014  Cd Length: 62  Bit Score: 39.11  E-value: 8.04e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062 1132 VIAMYDYAANnEDEL--------SFSKGQLINVMNKDDPDWWQGE----INGVTGLFPS 1178
Cdd:cd12081     2 VRAQFEYDPL-KDDLipckqagiRFRVGDILQIISKDDHNWWQAKlensKNGTAGLIPS 59
tolA_full TIGR02794
TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the ...
647-756 8.27e-04

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]


Pssm-ID: 274303 [Multi-domain]  Cd Length: 346  Bit Score: 43.68  E-value: 8.27e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   647 LKELRETCNTQQLA--LEQLYKIKRDKLKEIERkrleliQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKT 724
Cdd:TIGR02794   91 QKELEQRAAAEKAAkqAEQAAKQAEEKQKQAEE------AKAKQAAEAKAKAEAEAERKAKEEAAKQAEEEAKAKAAAEA 164
                           90       100       110
                   ....*....|....*....|....*....|...
gi 966980062   725 QEKIQEEERKAEEKQRKDKDTlkvEEK-QRETA 756
Cdd:TIGR02794  165 KKKAEEAKKKAEAEAKAKAEA---EAKaKAEEA 194
SH3_DNMBP_N4 cd11797
Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
764-809 8.51e-04

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212731  Cd Length: 50  Bit Score: 38.94  E-value: 8.51e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFP 809
Cdd:cd11797     4 ALYRFQALEPNELDFEVGDRIRI--IATLEDGWLEGELKGRRGIFP 47
CCDC47 pfam07946
PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of ...
665-738 8.52e-04

PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins. CCDC47 is required to maintain the stability of Asterix. CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis. It is also involved in the regulation of calcium ion homeostasis in the ER, being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway.


Pssm-ID: 462322  Cd Length: 323  Bit Score: 43.33  E-value: 8.52e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   665 YKIKRDKLKEIERKRLELIQKKKLEDEAAR--KAKQGKEnlwkENLRREEEEKQKRLQEEKtQEKIQEEERKAEEK 738
Cdd:pfam07946  252 AKLRPEALKKAKKTREEEIEKIKKAAEEERaeEAQEKKE----EAKKKEREEKLAKLSPEE-QRKYEEKERKKEQR 322
CCDC34 pfam13904
Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several ...
380-480 8.81e-04

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.


Pssm-ID: 464032 [Multi-domain]  Cd Length: 221  Bit Score: 42.77  E-value: 8.81e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   380 KRRQALVEQQQREAERKAQKEKEEWERKQRELQE--QEW---KKQLELEKRLEKQRELERQREEERRKEIERREAA---- 450
Cdd:pfam13904   62 AAKQRQRQKELQAQKEEREKEEQEAELRKRLAKEkyQEWlqrKARQQTKKREESHKQKAAESASKSLAKPERKVSQeeak 141
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 966980062   451 ---------KQELERQRRLEWER--IRRQELLNQKNREQEE 480
Cdd:pfam13904  142 evlqewerkKLEQQQRKREEEQReqLKKEEEEQERKQLAEK 182
SH3_Tks5_2 cd12077
Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
909-952 8.87e-04

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213010  Cd Length: 54  Bit Score: 38.86  E-value: 8.87e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 966980062  909 WTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd12077     9 YTSQGKDEIGFEKGVTVEVIQKNlEGWWYIRYLGKEGWAPASYLK 53
SH3_Shank cd11832
Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank ...
986-1031 8.95e-04

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212766  Cd Length: 50  Bit Score: 38.57  E-value: 8.95e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQ-KDGEWWTGSIGDRSGIFPS 1031
Cdd:cd11832     2 FIAVKSYSPQEEGEISLHKGDRVKVLSiGEGGFWEGSVRGRTGWFPS 48
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
1587-1654 9.02e-04

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 41.09  E-value: 9.02e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966980062 1587 NGKSNPYCEISMGSQSYTTRTIQDTLNPKWNfncQFFIKDLY-----QDVLCLTLFDRDQFSPDDFLGRTEIP 1654
Cdd:cd08373    12 KGKGDRIAKVTFRGVKKKTRVLENELNPVWN---ETFEWPLAgspdpDESLEIVVKDYEKVGRNRLIGSATVS 81
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
1064-1113 9.15e-04

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 39.05  E-value: 9.15e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELqarGKKRQKgWFPASHVK 1113
Cdd:cd11969     8 YRAKRSDELSFCKGALIHNVSKETGGWWKGDY---GGKVQH-YFPSNYVE 53
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
1569-1650 9.29e-04

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 41.23  E-value: 9.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMG------SQSYTTRTiQDTLNPKWNFNCQFFIK-DLYQDV-LCLTLFDRD 1640
Cdd:cd08402    15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLMqngkrlKKKKTTIK-KRTLNPYYNESFSFEVPfEQIQKVhLIVTVLDYD 93
                          90
                  ....*....|
gi 966980062 1641 QFSPDDFLGR 1650
Cdd:cd08402    94 RIGKNDPIGK 103
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
905-952 9.34e-04

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212925  Cd Length: 52  Bit Score: 38.84  E-value: 9.34e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11992     4 ALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
1056-1108 9.44e-04

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 39.04  E-value: 9.44e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1056 EIAQVTSAYVASGSEQLSLAPGQLILILKKNT--SGWWQGELQARgkkrqKGWFP 1108
Cdd:cd12056     2 EYCKALFHYEGTNEDELDFKEGEIILIISKDTgePGWWKGELNGK-----EGVFP 51
SH3_CASS4 cd12000
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ...
901-953 9.55e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212933  Cd Length: 57  Bit Score: 39.09  E-value: 9.55e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  901 LKAQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd12000     1 LLARALYDNKADCSDELAFRRGDILTVLEQNvpgsEGWWKCLLHGRQGLAPANRLQL 57
SH3_FCHSD1_2 cd11895
Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain ...
763-816 9.69e-04

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212828  Cd Length: 58  Bit Score: 38.79  E-value: 9.69e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGE--PGWLYGSFQGNFGWFPCNYVEKM 816
Cdd:cd11895     3 RALYSYTGQSPEELSFPEGALIRLLPRAQDGvdDGFWRGEFGGRVGVFPSLLVEEL 58
CCDC34 pfam13904
Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several ...
647-757 9.74e-04

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.


Pssm-ID: 464032 [Multi-domain]  Cd Length: 221  Bit Score: 42.38  E-value: 9.74e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   647 LKELRETCNTQQLALEQLyKIKRDKLKEiERKRL------ELIQKKKLEDEAARKAKQGKENLWKEN------LRREEEE 714
Cdd:pfam13904   61 LAAKQRQRQKELQAQKEE-REKEEQEAE-LRKRLakekyqEWLQRKARQQTKKREESHKQKAAESASkslakpERKVSQE 138
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 966980062   715 KQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETAS 757
Cdd:pfam13904  139 EAKEVLQEWERKKLEQQQRKREEEQREQLKKEEEEQERKQLAE 181
SH3_Brk cd11847
Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called ...
762-789 9.80e-04

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212781 [Multi-domain]  Cd Length: 58  Bit Score: 39.08  E-value: 9.80e-04
                          10        20
                  ....*....|....*....|....*...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEK 789
Cdd:cd11847     2 YKALWDFKARGDEELSFQAGDQFRIAER 29
TolA COG3064
Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];
668-756 9.94e-04

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];


Pssm-ID: 442298 [Multi-domain]  Cd Length: 485  Bit Score: 43.87  E-value: 9.94e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  668 KRDKLKEIERKRLELIQKKKLED-----EAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKD 742
Cdd:COG3064    24 EKRAAAEAEQKAKEEAEEERLAEleakrQAEEEAREAKAEAEQRAAELAAEAAKKLAEAEKAAAEAEKKAAAEKAKAAKE 103
                          90
                  ....*....|....
gi 966980062  743 KDTLKVEEKQRETA 756
Cdd:COG3064   104 AEAAAAAEKAAAAA 117
SH3_Vinexin_3 cd11918
Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain ...
983-1036 9.95e-04

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212851 [Multi-domain]  Cd Length: 58  Bit Score: 38.79  E-value: 9.95e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  983 GEEYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGsIGDRS---GIFPSNYVKP 1036
Cdd:cd11918     1 RTPYKAVYQYRPQNEDELELREGDRVDVMQQcDDGWFVG-VSRRTqkfGTFPGNYVAP 57
DUF3584 pfam12128
Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. ...
377-755 1.00e-03

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.


Pssm-ID: 432349 [Multi-domain]  Cd Length: 1191  Bit Score: 44.06  E-value: 1.00e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   377 ELEKRRQALVEQQQREAERKAQKEKEEWERKQREL---------QEQEWKKQLELEKRlekqrelerqreeerrkeierr 447
Cdd:pfam12128  376 KYNRRRSKIKEQNNRDIAGIKDKLAKIREARDRQLavaeddlqaLESELREQLEAGKL---------------------- 433
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   448 EAAKQELERQRRLEWERIR------RQELLNQK-------NREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRL 514
Cdd:pfam12128  434 EFNEEEYRLKSRLGELKLRlnqataTPELLLQLenfderiERAREEQEAANAEVERLQSELRQARKRRDQASEALRQASR 513
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   515 KKQTQKTELE----VLDKQCDLEIMEIKQLQQELQEYQNKLIylVPEkQLLNERIKNMQFSNTPDSGVSL----LHKKSL 586
Cdd:pfam12128  514 RLEERQSALDelelQLFPQAGTLLHFLRKEAPDWEQSIGKVI--SPE-LLHRTDLDPEVWDGSVGGELNLygvkLDLKRI 590
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   587 EKQE---LCQRLKEQLDALEK--ETASKL-----SEMDSYNNQLKCGNMDDS-VLQCLLSLLSCLNNLFLLLKELRETCN 655
Cdd:pfam12128  591 DVPEwaaSEEELRERLDKAEEalQSAREKqaaaeEQLVQANGELEKASREETfARTALKNARLDLRRLFDEKQSEKDKKN 670
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   656 tQQLALEQLYKIKRDKLKEIERKRLELIQKKKLE--DEAARKAKQGKENLWKE-------NLRREEEEKQKRLQEEKTQE 726
Cdd:pfam12128  671 -KALAERKDSANERLNSLEAQLKQLDKKHQAWLEeqKEQKREARTEKQAYWQVvegaldaQLALLKAAIAARRSGAKAEL 749
                          410       420       430
                   ....*....|....*....|....*....|
gi 966980062   727 KIQEEERKAEEKQRK-DKDTLKVEEKQRET 755
Cdd:pfam12128  750 KALETWYKRDLASLGvDPDVIAKLKREIRT 779
KLF3_N cd21577
N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called ...
91-184 1.06e-03

N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called Krueppel-like factor 3 and originally called Basic Kruppel-like Factor/BKLF), was the third member of the KLF family of zinc finger transcription factors to be discovered. KLF3 possesses a wide range of biological impacts on regulating apoptosis, differentiation, and proliferation in various tissues during the entire progression process. It has been proposed as a tumor suppressor in colorectal cancer. It appears to function predominantly as a repressor of transcription, turning genes off by recruiting the C-terminal Binding Protein co-repressors CtBP1 and CtBP2. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, through the Proline-X-Aspartate-Leucine-Serine (PXDLS) motif. CtBP in turn recruits histone modifying enzymes to alter chromatin and repress gene expression. KLF3 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF3.


Pssm-ID: 410554 [Multi-domain]  Cd Length: 214  Bit Score: 42.33  E-value: 1.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   91 QGQQLPVVL-------PPimkqPPMFSPLISARFGMGSMPNLSIPQP---LPPAAPITSLSSATSGTnLPPLMMPAPLVP 160
Cdd:cd21577    16 HSQLEPVDLslskrssPP----SSSSSSSSSSSSSSSPSSRASPPSPyskSSPPSPPQQRPLSPPLS-LPPPVAPPPLSP 90
                          90       100
                  ....*....|....*....|....
gi 966980062  161 SVSTSSLPNGTASLIQPLSIPYSS 184
Cdd:cd21577    91 GSVPGGLPVISPVMVQPVPVLYPP 114
SH3_Sla1p_2 cd11774
Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
763-813 1.07e-03

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212708 [Multi-domain]  Cd Length: 52  Bit Score: 38.60  E-value: 1.07e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGW-LYGSFQGNFGWFPCNYV 813
Cdd:cd11774     3 KALYDYDKQTEEELSFNEGDTLDVYDDS--DSDWiLVGFNGTQFGFVPANYI 52
TolA COG3064
Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];
348-522 1.07e-03

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];


Pssm-ID: 442298 [Multi-domain]  Cd Length: 485  Bit Score: 43.49  E-value: 1.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  348 QKIQEEEPQKKLPvTFEDKRKAN---YERGNMELEKRRQALVEQQqREAERKAQKEKEEWERKQRELQEQEWKKQLELEK 424
Cdd:COG3064     7 EKAAEAAAQERLE-QAEAEKRAAaeaEQKAKEEAEEERLAELEAK-RQAEEEAREAKAEAEQRAAELAAEAAKKLAEAEK 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  425 RLEKqrelerqreeerRKEIERREAAKQELERQRRLEWERIR---RQELLNQKNREQEEIVRLNSKKKSLHLELEALNGK 501
Cdd:COG3064    85 AAAE------------AEKKAAAEKAKAAKEAEAAAAAEKAAaaaEKEKAEEAKRKAEEEAKRKAEEERKAAEAEAAAKA 152
                         170       180
                  ....*....|....*....|.
gi 966980062  502 HQQISGRLQDVRLKKQTQKTE 522
Cdd:COG3064   153 EAEAARAAAAAAAAAAAAAAR 173
SH3_Sorbs1_3 cd11916
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), ...
904-954 1.08e-03

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212849 [Multi-domain]  Cd Length: 59  Bit Score: 38.82  E-value: 1.08e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQENWWF-GEVHGGR--GWFPKSYVKII 954
Cdd:cd11916     5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFvGTSRRTKqfGTFPGNYVKLL 58
SH3_CIP4-like cd11911
Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of ...
763-796 1.08e-03

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212844 [Multi-domain]  Cd Length: 55  Bit Score: 38.78  E-value: 1.08e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGW 796
Cdd:cd11911     3 TALYDFDGTSEGTLSMEEGEILLVLEEDGGD-GW 35
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
904-951 1.09e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212978  Cd Length: 53  Bit Score: 38.73  E-value: 1.09e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 951
Cdd:cd12045     3 QGLWDCTGDQPDELSFKRGDTIYILSKEYNrfgWWVGEMKGTIGLVPKAYI 53
SH3_Tks_1 cd12015
First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
1060-1111 1.11e-03

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212948  Cd Length: 53  Bit Score: 38.55  E-value: 1.11e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1060 VTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQargkkRQKGWFPASH 1111
Cdd:cd12015     4 VVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLE-----DEQGWVPATY 50
SH3_Eve1_2 cd11815
Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
765-814 1.11e-03

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212749 [Multi-domain]  Cd Length: 52  Bit Score: 38.70  E-value: 1.11e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  765 LYPFEARNHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11815     5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTE--WYRGKCKNTTGIFPANHVK 52
SH3_p67phox-like_C cd11870
C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; ...
902-952 1.14e-03

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212803 [Multi-domain]  Cd Length: 53  Bit Score: 38.66  E-value: 1.14e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11870     1 QVVALHRYEAQGPEDLGFREGDTIDVLSEvNEAWLEGHSDGRVGIFPKCFVV 52
MAP7 pfam05672
MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is ...
689-754 1.16e-03

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.


Pssm-ID: 461709 [Multi-domain]  Cd Length: 153  Bit Score: 41.18  E-value: 1.16e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   689 EDEAAR----KAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRE 754
Cdd:pfam05672    9 AEEAARilaeKRRQAREQREREEQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQ 78
SH3_ephexin1 cd11939
Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called ...
1059-1113 1.18e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212872 [Multi-domain]  Cd Length: 55  Bit Score: 38.77  E-value: 1.18e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1059 QVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGElqaRGKKRQKGWFPASHVK 1113
Cdd:cd11939     3 QCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGE---RLHDQERGWFPSSVVE 54
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
1569-1649 1.19e-03

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 40.95  E-value: 1.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGSQ-----SYTTRTIQDTLNPKWNFNCQFFIKDLYQDVLCLTL--FDRDQ 1641
Cdd:cd08403    14 GRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEgrrlkKKKTSVKKNTLNPTYNEALVFDVPPENVDNVSLIIavVDYDR 93

                  ....*...
gi 966980062 1642 FSPDDFLG 1649
Cdd:cd08403    94 VGHNELIG 101
SH3_EFS cd12003
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
988-1035 1.19e-03

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212936  Cd Length: 62  Bit Score: 38.72  E-value: 1.19e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE----WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12003     5 ALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLR 56
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
903-950 1.24e-03

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 38.23  E-value: 1.24e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSY 950
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHLDaEWSRGRLNGREGIFPRAF 50
SH3_EFS cd12003
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
763-819 1.31e-03

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212936  Cd Length: 62  Bit Score: 38.72  E-value: 1.31e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTIGE-PGWLYGSFQGNFGWFPCNYVEKMPSS 819
Cdd:cd12003     4 KALYDNAAESPEELSFRRGDVLMVLKREHGSlPGWWLCSLHGQQGIAPANRLRLLPTA 61
SH3_p40phox cd11869
Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil ...
988-1035 1.32e-03

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212802  Cd Length: 54  Bit Score: 38.24  E-value: 1.32e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11869     4 ALFDFTGNSKLELNFKAGDVIfLLSRVNKDWLEGTVRGATGIFPLSFVK 52
SH3_Endophilin_B cd11802
Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, ...
1134-1180 1.32e-03

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212736 [Multi-domain]  Cd Length: 52  Bit Score: 38.42  E-value: 1.32e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11802     4 VLYDYDAEDSTELSLLADEVITVYELPgmDEDYMMGERGSQRGKVPVAY 52
Caldesmon pfam02029
Caldesmon;
400-751 1.32e-03

Caldesmon;


Pssm-ID: 460421 [Multi-domain]  Cd Length: 495  Bit Score: 43.32  E-value: 1.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   400 EKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEW----ERIRRQELLNQKN 475
Cdd:pfam02029    5 EEAARERRRRAREERRRQKEEEEPSGQVTESVEPNEHNSYEEDSELKPSGQGGLDEEEAFLDRtakrEERRQKRLQEALE 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   476 REQEEIVRLNSKKKSLHLELEALN-------GKHQQISGRLQDV------RLKKQTQKTELEVLDKQCDLEIMEIKQLQq 542
Cdd:pfam02029   85 RQKEFDPTIADEKESVAERKENNEeeensswEKEEKRDSRLGRYkeeeteIREKEYQENKWSTEVRQAEEEGEEEEDKS- 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   543 elqeyqnKLIYLVPEKQLLNERIKNMQFSNTpdsgvslLHKKSLEKQELCQRlkeqldALEKETASKLSEMDSYNNQLKC 622
Cdd:pfam02029  164 -------EEAEEVPTENFAKEEVKDEKIKKE-------KKVKYESKVFLDQK------RGHPEVKSQNGEEEVTKLKVTT 223
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   623 GNMDDSVLQCllsllsclnnlflllkELRETCNTQQLALEQ-LYKIKRdKLKEIERKRLELIQKKKLE-----DEAARKA 696
Cdd:pfam02029  224 KRRQGGLSQS----------------QEREEEAEVFLEAEQkLEELRR-RRQEKESEEFEKLRQKQQEaelelEELKKKR 286
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   697 KQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEE-ERK----AEEKQRKDKDTLKVEEK 751
Cdd:pfam02029  287 EERRKLLEEEEQRRKQEEAERKLREEEEKRRMKEEiERRraeaAEKRQKLPEDSSSEGKK 346
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
988-1035 1.32e-03

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212827  Cd Length: 56  Bit Score: 38.38  E-value: 1.32e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILV----TQKDGEWWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11894     4 ALYDYEGQTDDELSFPEGAIIRIlnkeNQDDDGFWEGEFNGRIGVFPSVLVE 55
SH3_MIA_like cd11760
Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a ...
1127-1182 1.44e-03

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.


Pssm-ID: 212694  Cd Length: 76  Bit Score: 39.00  E-value: 1.44e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1127 HPVCQVIAMYDYAANNEDELSFSKGQLINVMNK---DDPDWWQGEINGVTGL---FPSNYVK 1182
Cdd:cd11760     9 NPISRARALEDYHGPDCRFLNFKKGDTIYVYSKlagERQDLWAGSVGGDAGLfgyFPKNLVQ 70
SH3_SH3RF_C cd11785
C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), ...
1138-1182 1.45e-03

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212719  Cd Length: 55  Bit Score: 38.22  E-value: 1.45e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062 1138 YAANNEDELSFSKGQLINVMNKDDPDWWQGEI--NGVTGLFPSNYVK 1182
Cdd:cd11785     8 YPPQSEAELELKEGDIVFVHKKREDGWFKGTLqrTGKTGLFPGSFVE 54
SH3_ARHGEF5_19 cd11940
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ...
768-814 1.50e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212873  Cd Length: 55  Bit Score: 38.23  E-value: 1.50e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  768 FEARNHDEMSFNSGDIIQVdeKTIGEPGWLYGS--FQGNFGWFPCNYVE 814
Cdd:cd11940     8 YKAQENDELTLEKADIIMV--RQQSSDGWLEGVrlSDGERGWFPQSHVE 54
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
986-1036 1.51e-03

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212858  Cd Length: 57  Bit Score: 38.44  E-value: 1.51e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTGSIGDR---SGIFPSNYVKP 1036
Cdd:cd11925     3 YLALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRtgvSGVFPGNYVTP 56
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
985-1034 1.52e-03

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 38.11  E-value: 1.52e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGE--EILVTQKDGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11804     1 EAVAKHDFKATAEDELSFKKGSilKVLNMEDDPNWYKAELDGKEGLIPKNYI 52
SH3_Endophilin_B2 cd11944
Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain ...
1134-1183 1.53e-03

Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212877  Cd Length: 55  Bit Score: 38.44  E-value: 1.53e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKD--DPDWWQGEINGVTGLFPSNYVKM 1183
Cdd:cd11944     4 VLYDYEAADSSELALLADELITVYSLPgmDPDWLIGERGNQKGKVPVTYLEL 55
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
766-815 1.54e-03

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 38.34  E-value: 1.54e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  766 YPFEARNHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12052     6 FDYKAQHEDELTITVGDIITKIKKDDG--GWWEGEIKGRRGLFPDNFVRE 53
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
587-756 1.58e-03

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 43.22  E-value: 1.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  587 EKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKcgnmddsvlqcllsllscLNNLFLLLKELRETCNTQQLALEQLY- 665
Cdd:COG4717    92 ELQEELEELEEELEELEAELEELREELEKLEKLLQ------------------LLPLYQELEALEAELAELPERLEELEe 153
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  666 KIK--RDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDK 743
Cdd:COG4717   154 RLEelRELEEELEELEAELAELQEELEELLEQLSLATEEELQDLAEELEELQQRLAELEEELEEAQEELEELEEELEQLE 233
                         170
                  ....*....|...
gi 966980062  744 DTLKVEEKQRETA 756
Cdd:COG4717   234 NELEAAALEERLK 246
ERM_helical pfam20492
Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related ...
648-752 1.59e-03

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.


Pssm-ID: 466641 [Multi-domain]  Cd Length: 120  Bit Score: 39.90  E-value: 1.59e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   648 KELRETCNTQQLALEQLYKIKRDKlKEIERKRLELIQ-KKKLEDEAARKAKQgkenlwKENLRREEEEKQkrlqeEKTQE 726
Cdd:pfam20492   27 EELEESEETAEELEEERRQAEEEA-ERLEQKRQEAEEeKERLEESAEMEAEE------KEQLEAELAEAQ-----EEIAR 94
                           90       100
                   ....*....|....*....|....*.
gi 966980062   727 KIQEEERKAEEKQRKDKDTLKVEEKQ 752
Cdd:pfam20492   95 LEEEVERKEEEARRLQEELEEAREEE 120
SH3_SH3RF1_3 cd11926
Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ...
762-813 1.63e-03

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212859 [Multi-domain]  Cd Length: 55  Bit Score: 38.03  E-value: 1.63e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYV 813
Cdd:cd11926     2 YVAIYPYTPRKEDELELRKGEMFLVFERC--QDGWFKGTsmHTSKIGVFPGNYV 53
EF-hand_7 pfam13499
EF-hand domain pair;
247-306 1.67e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 38.39  E-value: 1.67e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062   247 KYRQKFNSLDKSMSGYLSG--FQA--RNALLQSNLSQTQLATIWTLADIDGDGQLKAEEFILAM 306
Cdd:pfam13499    3 KLKEAFKLLDSDGDGYLDVeeLKKllRKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
DUF612 pfam04747
Protein of unknown function, DUF612; This family includes several uncharacterized proteins ...
670-756 1.68e-03

Protein of unknown function, DUF612; This family includes several uncharacterized proteins from Caenorhabditis elegans.


Pssm-ID: 282585 [Multi-domain]  Cd Length: 511  Bit Score: 43.13  E-value: 1.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   670 DKLKEIERKRlelIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVE 749
Cdd:pfam04747   68 EKVKKSEKKK---AQKQIAKDHEAEQKVNAKKAAEKEARRAEAEAKKRAAQEEEHKQWKAEQERIQKEQEKKEADLKKLQ 144

                   ....*...
gi 966980062   750 -EKQRETA 756
Cdd:pfam04747  145 aEKKKEKA 152
SH3_Sla1p_2 cd11774
Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
988-1034 1.70e-03

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212708 [Multi-domain]  Cd Length: 52  Bit Score: 38.21  E-value: 1.70e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILV-TQKDGEW-WTGSIGDRSGIFPSNYV 1034
Cdd:cd11774     4 ALYDYDKQTEEELSFNEGDTLDVyDDSDSDWiLVGFNGTQFGFVPANYI 52
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
903-951 1.73e-03

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212727 [Multi-domain]  Cd Length: 55  Bit Score: 38.09  E-value: 1.73e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGE--VHGGRGWFPKSYV 951
Cdd:cd11793     2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMpDGWYEGErlRDGERGWFPSSYT 53
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
1556-1658 1.75e-03

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 40.69  E-value: 1.75e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1556 KAYQARS--QKTSGI--GRLMVHVIEATELkackpngkSNPYCEISMGSQSYTTRTIQDTLNPKWN----FNCQFfiKDL 1627
Cdd:cd04018     5 KIYRAEDlpQMDSGImaNVKKAFLGEKKEL--------VDPYVEVSFAGQKVKTSVKKNSYNPEWNeqivFPEMF--PPL 74
                          90       100       110
                  ....*....|....*....|....*....|.
gi 966980062 1628 YQdVLCLTLFDRDQFSPDDFLGRTEIPVAKI 1658
Cdd:cd04018    75 CE-RIKIQIRDWDRVGNDDVIGTHFIDLSKI 104
SH3_RUSC2 cd11957
Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or ...
985-1034 1.77e-03

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212890  Cd Length: 52  Bit Score: 37.97  E-value: 1.77e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11957     1 EVKALCHHIATEPGQLSFNKGDILQVLSRaDGDWLRCSLGPDSGLVPIAYV 51
SH3_CIP4_Bzz1_like cd11777
Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily ...
1131-1183 1.82e-03

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212711 [Multi-domain]  Cd Length: 55  Bit Score: 37.97  E-value: 1.82e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQ--GEINGVTGLFPSNYVKM 1183
Cdd:cd11777     1 ECKALYAFVGSSEGTISMTEGEKLSLVEEDKGDGWTrvRRDTGEEGYVPTSYIRI 55
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
988-1035 1.85e-03

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 38.05  E-value: 1.85e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGI-FPSNYVK 1035
Cdd:cd11970     8 ALFDYKAQREDELTFTKNAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYVE 57
PRK12704 PRK12704
phosphodiesterase; Provisional
377-526 1.88e-03

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 42.84  E-value: 1.88e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  377 ELEKRRQALVEQQQREAERKAQKE----KEEWERKQRELqEQEWKkqlelEKRLEkqrelerqreeerrkeIerreaakQ 452
Cdd:PRK12704   35 EAEEEAKRILEEAKKEAEAIKKEAlleaKEEIHKLRNEF-EKELR-----ERRNE----------------L-------Q 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062  453 ELErqRRLewerIRRQELLNQKNREqeeivrLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVL 526
Cdd:PRK12704   86 KLE--KRL----LQKEENLDRKLEL------LEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERI 147
SH3_Caskin2 cd12063
Src Homology 3 domain of CASK interacting protein 2; Caskin2 is a multidomain adaptor protein ...
901-954 1.90e-03

Src Homology 3 domain of CASK interacting protein 2; Caskin2 is a multidomain adaptor protein that contains six ankyrin repeats, a single SH3 domain, tandem sterile alpha motif (SAM) domains, and a long disordered proline-rich region. It shares a domain architecture with Caskin1, but does not bind CASK. The function of Caskin2 is still unknown. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212996  Cd Length: 62  Bit Score: 38.41  E-value: 1.90e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062  901 LKAQALCS-WTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGR------GWFPKSYVKII 954
Cdd:cd12063     1 LKVRALKDfWNLHDPTALNVRAGDVITVLEQHpDGRWKGHIHDSQrgtdrvGYFPPSIVEVI 62
UDM1_RNF168 cd22265
UDM1 (ubiquitin-dependent DSB recruitment module 1) domain found in RING finger protein 168; ...
691-746 1.90e-03

UDM1 (ubiquitin-dependent DSB recruitment module 1) domain found in RING finger protein 168; RING finger protein 168 (RNF168) is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. Together with RNF8, RNF168 functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates such as H2A and H2AX. With H2AK13/15 ubiquitylation, it facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. In addition, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. This model corresponds to the UDM1 (ubiquitin-dependent double-strand break [DSB] recruitment module 1) domain of RNF168, which comprises LRM1 (LR motif 1), UMI (ubiquitin-interacting motif [UIM]- and MIU-related UBD) and MIU1 (motif interacting with ubiquitin 1). Mutations of Ub-interacting residues in UDM1 have little effect on the accumulation of RNF168 to DSB sites, suggesting that it may not be the main site of binding ubiquitylated and polyubiquitylated targets.


Pssm-ID: 409018 [Multi-domain]  Cd Length: 73  Bit Score: 38.69  E-value: 1.90e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  691 EAARKAKQGKENlwkenlRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTL 746
Cdd:cd22265    19 EAERRALEEEEN------RASEEYIQKLLAEEEEEEKLAEERRRAEEEQLKEDEEL 68
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
986-1035 2.03e-03

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212921 [Multi-domain]  Cd Length: 57  Bit Score: 37.93  E-value: 2.03e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  986 YIALYPYSSVEPGDLTFTEGEEILVTQKD-GE--WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11988     4 YRALYPFEARNHDEMSFNAGDIIQVDEKTvGEpgWLYGSFQGNFGWFPCNYVE 56
SH3_ARHGEF5_19 cd11940
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ...
904-952 2.04e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212873  Cd Length: 55  Bit Score: 37.85  E-value: 2.04e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVH---GGRGWFPKSYVK 952
Cdd:cd11940     3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRlsdGERGWFPQSHVE 54
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
990-1034 2.04e-03

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 38.06  E-value: 2.04e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062  990 YPYSSVEPGDLTFTEGEEILVTQK--DGeWWTGSIGDRSGIFPSNYV 1034
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKcsDG-WWRGSYNGQIGWFPSNYV 52
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
763-815 2.05e-03

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 38.05  E-value: 2.05e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIEVVGEV--EEGWWEGVLNGKTGMFPSNFIKE 53
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
1569-1653 2.06e-03

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 40.26  E-value: 2.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEATELKACKPNGKSNPYCEISMGS-----QSYTTRTIQDTLNPKWNFNCQFFI--KDLYQDVLCLTLFDRDQ 1641
Cdd:cd08410    14 GRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHglkliKTKKTSCMRGTIDPFYNESFSFKVpqEELENVSLVFTVYGHNV 93
                          90
                  ....*....|..
gi 966980062 1642 FSPDDFLGRTEI 1653
Cdd:cd08410    94 KSSNDFIGRIVI 105
SH3_Nbp2-like cd11865
Src Homology 3 domain of Saccharomyces cerevisiae Nap1-binding protein 2 and similar fungal ...
1131-1183 2.07e-03

Src Homology 3 domain of Saccharomyces cerevisiae Nap1-binding protein 2 and similar fungal proteins; This subfamily includes Saccharomyces cerevisiae Nbp2 (Nucleosome assembly protein 1 (Nap1)-binding protein 2), Schizosaccharomyces pombe Skb5, and similar proteins. Nbp2 interacts with Nap1, which is essential for maintaining proper nucleosome structures in transcription and replication. It is also the binding partner of the yeast type II protein phosphatase Ptc1p and serves as a scaffolding protein that brings seven kinases in close contact to Ptc1p. Nbp2 plays a role many cell processes including organelle inheritance, mating hormone response, cell wall stress, mitotic cell growth at elevated temperatures, and high osmolarity. Skb5 interacts with the p21-activated kinase (PAK) homolog Shk1, which is critical for fission yeast cell viability. Skb5 activates Shk1 and plays a role in regulating cell morphology and growth under hypertonic conditions. Nbp2 and Skb5 contain an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212799  Cd Length: 55  Bit Score: 37.88  E-value: 2.07e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWW--QGEINGVTGLFPSNYVKM 1183
Cdd:cd11865     1 RAVALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 55
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
987-1034 2.18e-03

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212695 [Multi-domain]  Cd Length: 57  Bit Score: 37.73  E-value: 2.18e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEI-LVTQKDGEWWTGSIGDRS--GIFPSNYV 1034
Cdd:cd11761     5 KVLYSYEAQRPDELTITEGEELeVIEDGDGDGWVKARNKSGevGYVPENYL 55
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
485-757 2.20e-03

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 42.44  E-value: 2.20e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  485 NSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLiylvpekQLLNER 564
Cdd:COG4942    19 ADAAAEAEAELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAEL-------AELEKE 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  565 IKNMQfsntpdsgvsllhkKSLEKQElcQRLKEQLDALEKetaskLSEMDSYNNQLKCGNMDDSVlqcllsllsclnNLF 644
Cdd:COG4942    92 IAELR--------------AELEAQK--EELAELLRALYR-----LGRQPPLALLLSPEDFLDAV------------RRL 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  645 LLLKELRETCNTQqlaLEQLykikRDKLKEIERKRLEL-IQKKKLEDEAARKAKQgkenlwKENLRREEEEKQKRLQEEK 723
Cdd:COG4942   139 QYLKYLAPARREQ---AEEL----RADLAELAALRAELeAERAELEALLAELEEE------RAALEALKAERQKLLARLE 205
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 966980062  724 TQEKIQEEERKAEEKQRKDKDTL--KVEEKQRETAS 757
Cdd:COG4942   206 KELAELAAELAELQQEAEELEALiaRLEAEAAAAAE 241
SH3_SH3RF_C cd11785
C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), ...
762-815 2.28e-03

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212719  Cd Length: 55  Bit Score: 37.83  E-value: 2.28e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQ--GNFGWFPCNYVEK 815
Cdd:cd11785     2 YRVIVPYPPQSEAELELKEGDIVFVHKKR--EDGWFKGTLQrtGKTGLFPGSFVES 55
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
902-952 2.28e-03

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 37.70  E-value: 2.28e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd12076     2 KYTVIYPYTARDQDEINLEKGAVVEVIQKNlEGWWKIRYQGKEGWAPASYLK 53
GBP_C cd16269
Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal ...
379-490 2.30e-03

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.


Pssm-ID: 293879 [Multi-domain]  Cd Length: 291  Bit Score: 41.79  E-value: 2.30e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  379 EKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKqrelerqreeerrkeierreaaKQELERQR 458
Cdd:cd16269   195 EKEKEIEAERAKAEAAEQERKLLEEQQRELEQKLEDQERSYEEHLRQLKE----------------------KMEEEREN 252
                          90       100       110
                  ....*....|....*....|....*....|..
gi 966980062  459 RLEweriRRQELLNQKNREQEEIVRLNSKKKS 490
Cdd:cd16269   253 LLK----EQERALESKLKEQEALLEEGFKEQA 280
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
366-754 2.31e-03

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 42.74  E-value: 2.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  366 KRKANYERGNMELEKRRQAL---------VEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRLEKqrelerqr 436
Cdd:PRK03918  186 KRTENIEELIKEKEKELEEVlreineissELPELREELEKLEKEVKELEELKEEIEELE-KELESLEGSKRK-------- 256
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  437 eeerrkeierREAAKQELERQRR--------LEwERIRRQELLNQKNREQEEIVRL----NSKKKSLHLELEALNGKHQQ 504
Cdd:PRK03918  257 ----------LEEKIRELEERIEelkkeieeLE-EKVKELKELKEKAEEYIKLSEFyeeyLDELREIEKRLSRLEEEING 325
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  505 ISGRLQDVRlKKQTQKTELEVLDKQCDLEIMEIKqlqqELQEYQNKLIYLVPEKQLLNERIKNmqfsNTPDsgvsllhkK 584
Cdd:PRK03918  326 IEERIKELE-EKEERLEELKKKLKELEKRLEELE----ERHELYEEAKAKKEELERLKKRLTG----LTPE--------K 388
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  585 SLEKQELCQRLKEQLDALEKETASKLSEMDSYNNQLKCGNMDdsvlqcllsllsclnnlfllLKELRETCNTQQLALEql 664
Cdd:PRK03918  389 LEKELEELEKAKEEIEEEISKITARIGELKKEIKELKKAIEE--------------------LKKAKGKCPVCGRELT-- 446
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  665 ykikrdklkeiERKRLELIQKKKLEDEAARKAKQGKENLWKEnLRREEEEKQKRLQEEKT---QEKIQEEERKAEEKQRK 741
Cdd:PRK03918  447 -----------EEHRKELLEEYTAELKRIEKELKEIEEKERK-LRKELRELEKVLKKESElikLKELAEQLKELEEKLKK 514
                         410
                  ....*....|...
gi 966980062  742 dKDTLKVEEKQRE 754
Cdd:PRK03918  515 -YNLEELEKKAEE 526
SH3_Sorbs1_1 cd11919
First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; ...
763-814 2.34e-03

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212852 [Multi-domain]  Cd Length: 55  Bit Score: 37.64  E-value: 2.34e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  763 RALYPFEARNHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11919     4 RAKFDFKAQTLKELPLQKGDIVyiykQIDQN------WYEGEHHGRVGIFPRSYIE 53
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
391-741 2.39e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 42.75  E-value: 2.39e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   391 REAERKAQKEKEEWERKQRELQEqewkkqleLEKRLEkqreleRQReEERRKEIERREAAKQELER-QRRLEWERIRRQE 469
Cdd:TIGR02169  663 RGGILFSRSEPAELQRLRERLEG--------LKRELS------SLQ-SELRRIENRLDELSQELSDaSRKIGEIEKEIEQ 727
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   470 LLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLD--------KQCDLEIMEIKQLQ 541
Cdd:TIGR02169  728 LEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKLEEALNDLEarlshsriPEIQAELSKLEEEV 807
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   542 QELQEYQN----KLIYLVPEKQLLNERIKNMQFSNTPDSgvslLHKKSLEKQ-ELCQRLKEQLDALEKETASKLSEMDSY 616
Cdd:TIGR02169  808 SRIEARLReieqKLNRLTLEKEYLEKEIQELQEQRIDLK----EQIKSIEKEiENLNGKKEELEEELEELEAALRDLESR 883
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   617 NNQLKcGNMDDSVLQCLLSLLSCLNnlfllLKELRETCNTQQLALEQLYKIKRDKLKEIERKR------------LELIQ 684
Cdd:TIGR02169  884 LGDLK-KERDELEAQLRELERKIEE-----LEAQIEKKRKRLSELKAKLEALEEELSEIEDPKgedeeipeeelsLEDVQ 957
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966980062   685 KKKLEDEAARKAKQGKENL----WKENLRR--EEEEKQKRLQEEKTQekIQEEERKAEEKQRK 741
Cdd:TIGR02169  958 AELQRVEEEIRALEPVNMLaiqeYEEVLKRldELKEKRAKLEEERKA--ILERIEEYEKKKRE 1018
SH3_DNMBP_N4 cd11797
Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
987-1033 2.42e-03

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212731  Cd Length: 50  Bit Score: 37.40  E-value: 2.42e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILV--TQKDGeWWTGSIGDRSGIFPSNY 1033
Cdd:cd11797     3 VALYRFQALEPNELDFEVGDRIRIiaTLEDG-WLEGELKGRRGIFPHRF 50
C2_Tollip cd04016
C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 ...
1569-1655 2.44e-03

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175983 [Multi-domain]  Cd Length: 121  Bit Score: 39.62  E-value: 2.44e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1569 GRLMVHVIEAtelKACKPNG--KSNPYCEISMGSQSYTTRTIQD-TLNPKWNFNCQFFIKDLYqDVLCLTLFDRDQFSPD 1645
Cdd:cd04016     2 GRLSITVVQA---KLVKNYGltRMDPYCRIRVGHAVYETPTAYNgAKNPRWNKTIQCTLPEGV-DSIYIEIFDERAFTMD 77
                          90
                  ....*....|
gi 966980062 1646 DFLGRTEIPV 1655
Cdd:cd04016    78 ERIAWTHITI 87
ERM_helical pfam20492
Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related ...
651-755 2.45e-03

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.


Pssm-ID: 466641 [Multi-domain]  Cd Length: 120  Bit Score: 39.52  E-value: 2.45e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   651 RETCNTQQLALEQ-LYKIK------RDKLKEIERKRLELIQKKKLEDEAARK--AKQGKENLWKENLRR--EEEEKQKRL 719
Cdd:pfam20492    1 REEAEREKQELEErLKQYEeetkkaQEELEESEETAEELEEERRQAEEEAERleQKRQEAEEEKERLEEsaEMEAEEKEQ 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 966980062   720 QEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRET 755
Cdd:pfam20492   81 LEAELAEAQEEIARLEEEVERKEEEARRLQEELEEA 116
SH3_ephexin1 cd11939
Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called ...
902-952 2.46e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212872 [Multi-domain]  Cd Length: 55  Bit Score: 37.62  E-value: 2.46e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGE-VHGG-RGWFPKSYVK 952
Cdd:cd11939     1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDgWIFGErLHDQeRGWFPSSVVE 54
Cast pfam10174
RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part ...
557-775 2.48e-03

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.


Pssm-ID: 431111 [Multi-domain]  Cd Length: 766  Bit Score: 42.50  E-value: 2.48e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   557 EKQL--LNERIKNMQF-SNTPDSGVSLLHKKSLEKQELCQRLKEQLDALEKEtasKLSEMDSYNNQLKCGNMDDSVLQCL 633
Cdd:pfam10174  414 DKQLagLKERVKSLQTdSSNTDTALTTLEEALSEKERIIERLKEQREREDRE---RLEELESLKKENKDLKEKVSALQPE 490
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   634 LSLLSCLNNLFL---------------LLKEL-------RETCNTQQlalEQLYKIKrdKLKEIERKRLELIQK-KKLED 690
Cdd:pfam10174  491 LTEKESSLIDLKehasslassglkkdsKLKSLeiaveqkKEECSKLE---NQLKKAH--NAEEAVRTNPEINDRiRLLEQ 565
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   691 EAARKAK-----QGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQRKDKDTLKVEEKqRETASVLVNYRAL 765
Cdd:pfam10174  566 EVARYKEesgkaQAEVERLLGILREVENEKNDKDKKIAELESLTLRQMKEQNKKVANIKHGQQEMK-KKGAQLLEEARRR 644
                          250
                   ....*....|
gi 966980062   766 YPFEARNHDE 775
Cdd:pfam10174  645 EDNLADNSQQ 654
SH3_Shank3 cd11984
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also ...
1133-1181 2.51e-03

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212917  Cd Length: 52  Bit Score: 37.62  E-value: 2.51e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1133 IAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11984     4 IAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPADCV 52
Mplasa_alph_rch TIGR04523
helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...
377-754 2.57e-03

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.


Pssm-ID: 275316 [Multi-domain]  Cd Length: 745  Bit Score: 42.70  E-value: 2.57e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   377 ELEKRRQALVEQQQ--REAERKAQKEKEEWERKQRELQEqewkKQLELE------KRLEKQRELERQREeerrkeierre 448
Cdd:TIGR04523  233 NIEKKQQEINEKTTeiSNTQTQLNQLKDEQNKIKKQLSE----KQKELEqnnkkiKELEKQLNQLKSEI----------- 297
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   449 aakQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSlhleLEALNGKHQQISGRLQDVRLKKQTQKTELEvlDK 528
Cdd:TIGR04523  298 ---SDLNNQKEQDWNKELKSELKNQEKKLEEIQNQISQNNKI----ISQLNEQISQLKKELTNSESENSEKQRELE--EK 368
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   529 QcdleiMEIKQLQQELQEYQNKLIYLVPEKQLLNERIKNMQfsntpdsgvsllhKKSLEKQELCQRLKEQLDALEKETAS 608
Cdd:TIGR04523  369 Q-----NEIEKLKKENQSYKQEIKNLESQINDLESKIQNQE-------------KLNQQKDEQIKKLQQEKELLEKEIER 430
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   609 KLSEMDSYNNQLKCGNMDDSVLQCLLSLlsclnnlfllLKELRETCNTQQLALEQLYKIKRDKLKEIERkrlELIQKKKL 688
Cdd:TIGR04523  431 LKETIIKNNSEIKDLTNQDSVKELIIKN----------LDNTRESLETQLKVLSRSINKIKQNLEQKQK---ELKSKEKE 497
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062   689 EDEAARKAKQGKENLWKENLRREE-EEKQKRLQEEKTQ--EKIQEEERKAEE-KQRKDKDTLK--VEEKQRE 754
Cdd:TIGR04523  498 LKKLNEEKKELEEKVKDLTKKISSlKEKIEKLESEKKEkeSKISDLEDELNKdDFELKKENLEkeIDEKNKE 569
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
1064-1112 2.61e-03

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 37.69  E-value: 2.61e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNT-SGWWQGElQARGKkrqKGWFPASHV 1112
Cdd:cd11763     8 FDSQPSGELSLRAGEVLTITRQDVgDGWLEGR-NSRGE---VGLFPSSYV 53
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
987-1034 2.62e-03

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212839 [Multi-domain]  Cd Length: 55  Bit Score: 37.50  E-value: 2.62e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  987 IALYPYSSVEPGDLTFTEGEE-ILVTQKDGEWWTGSIGD-RSGIFPSNYV 1034
Cdd:cd11906     4 VALYDYTPMNAQDLQLRKGEEyVILEESNLPWWRARDKNgREGYIPSNYV 53
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
1063-1113 2.64e-03

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 37.34  E-value: 2.64e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHVK 1113
Cdd:cd11786     7 NYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNG-----KQGFFPASYVQ 52
SH3_Shank3 cd11984
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also ...
764-813 2.69e-03

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212917  Cd Length: 52  Bit Score: 37.62  E-value: 2.69e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11984     5 AVKAYSPQGEGEIQLNRGERVKV--LSIGEGGFWEGTVKGRTGWFPADCV 52
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
333-531 2.72e-03

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 42.59  E-value: 2.72e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  333 GGKQIDSINGTLpsYQKIQEEepqkklPVTFEDKRKAnyeRGNM-ELEKRRQALVE-QQQREAERKAQKEKEEWERKQRE 410
Cdd:COG4913   202 SFKPIGDLDDFV--REYMLEE------PDTFEAADAL---VEHFdDLERAHEALEDaREQIELLEPIRELAERYAAARER 270
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  411 LQEQEwkkqlELEKRLEKQrelerqreeerrkeierreaakqelERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKS 490
Cdd:COG4913   271 LAELE-----YLRAALRLW-------------------------FAQRRLELLEAELEELRAELARLEAELERLEARLDA 320
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062  491 LHLELEALNGKHQQISGR--------LQDVRLKKQTQKTELEVLDKQCD 531
Cdd:COG4913   321 LREELDELEAQIRGNGGDrleqlereIERLERELEERERRRARLEALLA 369
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
1063-1112 2.73e-03

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 37.28  E-value: 2.73e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1063 AYVASGSEQLSLAPGQLILILKKNTSGWWQGELqargkKRQKGWFPASHV 1112
Cdd:cd11772     7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKATC-----GGKTGLIPSNYV 51
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
763-814 2.89e-03

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212778  Cd Length: 56  Bit Score: 37.33  E-value: 2.89e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEK-TIGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11844     3 RALYDNVAESPDELAFRRGDILTVLEQnTAGLEGWWLCSLRGRQGIAPGNRLK 55
MAP7 pfam05672
MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is ...
351-489 2.91e-03

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.


Pssm-ID: 461709 [Multi-domain]  Cd Length: 153  Bit Score: 40.02  E-value: 2.91e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   351 QEEEPQKKLPvtfEDKRKANYERGNMELEKRRQAlVEQQQREAERKAQKEKEEWERKQRELQEQEwkkqlelekRLEKqr 430
Cdd:pfam05672   37 KEEEERLRKE---ELRRRAEEERARREEEARRLE-EERRREEEERQRKAEEEAEEREQREQEEQE---------RLQK-- 101
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   431 elerQreeerrkeierreaaKQELERQRRLEWERIRR-QELLNQKNrEQEeivRLNSKKK 489
Cdd:pfam05672  102 ----Q---------------KEEAEAKAREEAERQRQeREKIMQQE-EQE---RLERKKR 138
SH3_Shank2 cd11983
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also ...
762-813 2.95e-03

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212916  Cd Length: 52  Bit Score: 37.21  E-value: 2.95e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11983     3 FVVVKSYQPQVEGEIPLHKGDRVKV--LSIGEGGFWEGSARGHVGWFPAECV 52
PTZ00121 PTZ00121
MAEBL; Provisional
335-537 3.09e-03

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 42.44  E-value: 3.09e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  335 KQIDSINGTLPSYQKIQEEEPQKKLpvtfEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQ-- 412
Cdd:PTZ00121 1592 ARIEEVMKLYEEEKKMKAEEAKKAE----EAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEea 1667
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  413 --EQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRlEWERIRRQELLNQKNREQEEIVRLNSKKKS 490
Cdd:PTZ00121 1668 kkAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKK-KAEELKKAEEENKIKAEEAKKEAEEDKKKA 1746
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  491 LHLELEALNGK---HQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEI 537
Cdd:PTZ00121 1747 EEAKKDEEEKKkiaHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRMEV 1796
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
985-1035 3.11e-03

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212986  Cd Length: 56  Bit Score: 37.51  E-value: 3.11e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDGE--WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd12053     1 EYIVEYDYDAVHEDELTIRVGEIIRNVKKLEEegWLEGELNGRRGMFPDNFVK 53
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
763-814 3.14e-03

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212854  Cd Length: 55  Bit Score: 37.59  E-value: 3.14e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11921     4 RLKFDFQAQSPKELTLQKGDIVYIHKEV--DKNWLEGEHHGRVGIFPANYVE 53
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
985-1036 3.22e-03

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 37.37  E-value: 3.22e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  985 EYIALYPYSSVEPGDLTFTEGEEILVTQKDG-EWWTGSIGDRSGIFPSNYVKP 1036
Cdd:cd11806     1 EYVAIADFVATDDSQLSFESGDKLLVLRKPSvDWWWAEHNGCCGYIPASHLHQ 53
SH3_Tks_2 cd12016
Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
908-953 3.28e-03

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212949  Cd Length: 54  Bit Score: 37.44  E-value: 3.28e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062  908 SWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd12016     8 AYKAENEDEIGFETGVVVEVIQKNlDGWWKIRYQGKEGWAPATYLKK 54
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
1064-1113 3.34e-03

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 37.25  E-value: 3.34e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd11873     8 YDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGK-----RGMFPDNFVK 52
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
902-951 3.37e-03

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 37.24  E-value: 3.37e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITV-LEQQENWWFGEVHGG---RGWFPKSYV 951
Cdd:cd11966     1 RVKALYNCVADNPDELTFSEGEIIIVdGEEDKEWWIGHIDGEptrRGAFPVSFV 54
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
902-951 3.40e-03

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212822  Cd Length: 53  Bit Score: 37.09  E-value: 3.40e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEV--HGGRGWFPKSYV 951
Cdd:cd11889     1 KVKAVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKLrrNGAEGIFPSNFV 53
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
247-307 3.45e-03

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 37.53  E-value: 3.45e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966980062  247 KYRQKFNSLDKSMSGYLSGFQARNAL--LQSNLSQTQLATIWTLADIDGDGQLKAEEFILAMH 307
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
tolA PRK09510
cell envelope integrity inner membrane protein TolA; Provisional
684-756 3.59e-03

cell envelope integrity inner membrane protein TolA; Provisional


Pssm-ID: 236545 [Multi-domain]  Cd Length: 387  Bit Score: 41.72  E-value: 3.59e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062  684 QKKKLEDEAARKAKQGKENlwKENLRREEEEKQKRLQE-EKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETA 756
Cdd:PRK09510   70 QQKSAKRAEEQRKKKEQQQ--AEELQQKQAAEQERLKQlEKERLAAQEQKKQAEEAAKQAALKQKQAEEAAAKA 141
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
466-735 3.70e-03

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 41.67  E-value: 3.70e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  466 RRQELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQcdleimeIKQLQQElq 545
Cdd:COG4942    28 ELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKE-------IAELRAE-- 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  546 eyqnkliyLVPEKQLLNERIKNMQFSNTPDSGVSLLHKKSLEK--------QELCQRLKEQLDALEKETASklsemdsyn 617
Cdd:COG4942    99 --------LEAQKEELAELLRALYRLGRQPPLALLLSPEDFLDavrrlqylKYLAPARREQAEELRADLAE--------- 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  618 nqlkcgnmddsvlqcllsllsclnnlfllLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLEliqKKKLEDEAARKAK 697
Cdd:COG4942   162 -----------------------------LAALRAELEAERAELEALLAELEEERAALEALKAE---RQKLLARLEKELA 209
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 966980062  698 QGKENLwkENLRREEEEKQKRLQEEKTQEKIQEEERKA 735
Cdd:COG4942   210 ELAAEL--AELQQEAEELEALIARLEAEAAAAAERTPA 245
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
1131-1182 3.74e-03

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212713 [Multi-domain]  Cd Length: 57  Bit Score: 37.30  E-value: 3.74e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1131 QVIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQ---GEINGVTGLFPSNYVK 1182
Cdd:cd11779     2 RVKALYPHAAGGETQLSFEEGDVITLLGPEPRDGWHygeNERSGRRGWFPIAYTE 56
Remorin_C pfam03763
Remorin, C-terminal region; Remorins are plant-specific plasma membrane-associated proteins. ...
684-751 3.77e-03

Remorin, C-terminal region; Remorins are plant-specific plasma membrane-associated proteins. In tobacco remorin co-purifies with lipid rafts. Most remorins have a variable, proline-rich N-half and a more conserved C-half that is predicted to form coiled coils. Consistent with this, circular dichroism studies have demonstrated that much of the protein is alpha-helical. Remorins exist in plasma membrane preparations as oligomeric structures and form filaments in vitro. The proteins can bind polyanions including the extracellular matrix component oligogalacturonic acid (OGA). In vitro, remorin in plasma membrane preparations is phosphorylated (principally on threonine residues) in the presence of OGA and thus co-purifies with a protein kinases(s). The biological functions of remorins are unknown but roles as components of the membrane/cytoskeleton are possible.


Pssm-ID: 427493 [Multi-domain]  Cd Length: 106  Bit Score: 38.71  E-value: 3.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   684 QKKKLEDEAARK-AK-QGKENLWKE----NLRREEE--EKQKRLQEEKTQEKIQEEERKAEEKQ-----RKDKDTLKVEE 750
Cdd:pfam03763   13 EKAKIENRYKREeAKiQAWENLKKAkaeaELRKIEEklEKKRAEALEKMKNKLARIHKKAEEKRasaeaKRGEEELKTEE 92

                   .
gi 966980062   751 K 751
Cdd:pfam03763   93 K 93
PRK12704 PRK12704
phosphodiesterase; Provisional
661-761 3.80e-03

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 41.69  E-value: 3.80e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  661 LEQLYKIKRDKLKEIERKrleLIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQEEKTQEKIQEEERKAEE--- 737
Cdd:PRK12704   73 FEKELRERRNELQKLEKR---LLQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERisg 149
                          90       100
                  ....*....|....*....|....*..
gi 966980062  738 -KQRKDKDTL--KVEEKQRETASVLVN 761
Cdd:PRK12704  150 lTAEEAKEILleKVEEEARHEAAVLIK 176
Casc1_N pfam15927
Cancer susceptibility candidate 1 N-terminus; This presumed domain is functionally ...
706-749 3.86e-03

Cancer susceptibility candidate 1 N-terminus; This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is approximately 200 amino acids in length. The family is found in association with pfam12366. There are two completely conserved residues (N and W) that may be functionally important.


Pssm-ID: 464947 [Multi-domain]  Cd Length: 201  Bit Score: 40.42  E-value: 3.86e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 966980062   706 ENLRREEEEKQKRLQEEKtqEKIQEEERKAEEKQR--KDKDTLKVE 749
Cdd:pfam15927    1 ARLREEEEERLRAEEEEA--ERLEEERREEEEEERlaAEQDRRAEE 44
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
764-812 3.89e-03

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 37.36  E-value: 3.89e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  764 ALYPFEARNHDEMSFNSGDIIQV----DEKtigEPGWLYGSFQGNFGWFPCNY 812
Cdd:cd11807     5 ALFDYEAENGDELSFREGDELTVlrkgDDD---ETEWWWARLNDKEGYVPRNL 54
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
762-813 3.95e-03

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212941 [Multi-domain]  Cd Length: 56  Bit Score: 37.01  E-value: 3.95e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEpGWLYGSFQ-GNFGWFPCNYV 813
Cdd:cd12008     2 FVALYDYESRTETDLSFKKGERLQIVNNTEGD-WWLAHSLTtGQTGYIPSNYV 53
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1059-1113 3.96e-03

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 36.90  E-value: 3.96e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062 1059 QVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQARgkkrqKGWFPASHVK 1113
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGK-----TGMFPSNFIK 52
CwlO1 COG3883
Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function ...
468-740 3.97e-03

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];


Pssm-ID: 443091 [Multi-domain]  Cd Length: 379  Bit Score: 41.74  E-value: 3.97e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  468 QELLNQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQcdleimeikqlqqelqey 547
Cdd:COG3883    19 QAKQKELSELQAELEAAQAELDALQAELEELNEEYNELQAELEALQAEIDKLQAEIAEAEAE------------------ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  548 qnkliyLVPEKQLLNERIKNMQFSNTPDSGVS-LLHKKSLEkqelcqrlkeqlDALEKetASKLSEMDSYNNQLkcgnmd 626
Cdd:COG3883    81 ------IEERREELGERARALYRSGGSVSYLDvLLGSESFS------------DFLDR--LSALSKIADADADL------ 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  627 dsvlqcllsllsclnnlFLLLKELRETCNTQQLALEQlykikrdKLKEIERKRLELIQKKKlEDEAARKAKQGKENLWKE 706
Cdd:COG3883   135 -----------------LEELKADKAELEAKKAELEA-------KLAELEALKAELEAAKA-ELEAQQAEQEALLAQLSA 189
                         250       260       270
                  ....*....|....*....|....*....|....
gi 966980062  707 NLRREEEEKQKRLQEEKTQEKIQEEERKAEEKQR 740
Cdd:COG3883   190 EEAAAEAQLAELEAELAAAEAAAAAAAAAAAAAA 223
rad50 TIGR00606
rad50; All proteins in this family for which functions are known are involvedin recombination, ...
348-746 4.04e-03

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).


Pssm-ID: 129694 [Multi-domain]  Cd Length: 1311  Bit Score: 41.96  E-value: 4.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   348 QKIQEEEPQKKLPVTFEDKrkanyergnmELEKRRQALVEQQQREAERKAQKEKE----EWERKQRELQEQEwKKQLELE 423
Cdd:TIGR00606  200 QKVQEHQMELKYLKQYKEK----------ACEIRDQITSKEAQLESSREIVKSYEneldPLKNRLKEIEHNL-SKIMKLD 268
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   424 KRLEKQRELERQREEERRKEIERREAAKQELERQ------------RRLEWERIRRQELLNQKNREQEEivrLNSKKKSL 491
Cdd:TIGR00606  269 NEIKALKSRKKQMEKDNSELELKMEKVFQGTDEQlndlyhnhqrtvREKERELVDCQRELEKLNKERRL---LNQEKTEL 345
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   492 HLELEALNGKHQQISGRLQDVRLKKQTQKTELEV--------LDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNE 563
Cdd:TIGR00606  346 LVEQGRLQLQADRHQEHIRARDSLIQSLATRLELdgfergpfSERQIKNFHTLVIERQEDEAKTAAQLCADLQSKERLKQ 425
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   564 R-IKNMQFSNTPDSGVSLLHKKSLEK-QELCQRLKEQL--------DALEKETASKLSEMD----SYNNQLKCGNMDDSV 629
Cdd:TIGR00606  426 EqADEIRDEKKGLGRTIELKKEILEKkQEELKFVIKELqqlegssdRILELDQELRKAERElskaEKNSLTETLKKEVKS 505
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   630 LQCLLSLLSCLNNLfllLKELRETCNTQQLALEQLYKIKRDKLKEIERKR-------LELI-------QKKKLEDEAARK 695
Cdd:TIGR00606  506 LQNEKADLDRKLRK---LDQEMEQLNHHTTTRTQMEMLTKDKMDKDEQIRkiksrhsDELTsllgyfpNKKQLEDWLHSK 582
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|.
gi 966980062   696 AKQgkENLWKENLRREEEEKQKrlqEEKTQEKIQEEERKAEEKQRKDKDTL 746
Cdd:TIGR00606  583 SKE--INQTRDRLAKLNKELAS---LEQNKNHINNELESKEEQLSSYEDKL 628
SH3_Tks_3 cd12017
Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
1066-1112 4.06e-03

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212950  Cd Length: 53  Bit Score: 37.05  E-value: 4.06e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062 1066 ASGSEQLSLAPGQLILILKKNTSGWWQGELQArgkkrQKGWFPASHV 1112
Cdd:cd12017    10 ATIQDGISFQKGQKVEVIDKNPSGWWYVKIDG-----KEGWAPSSYI 51
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
1588-1672 4.08e-03

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176073 [Multi-domain]  Cd Length: 137  Bit Score: 39.31  E-value: 4.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1588 GKSNPYCEISM-------------GSQSYTTRTIQDTLNPKWNfNCQFFIKDLYQDVLCLTLfdRDQFSPD-----DFLG 1649
Cdd:cd08691    19 FNPDPYVKISIqpgkrhifpalphHGQECRTSIVENTINPVWH-REQFVFVGLPTDVLEIEV--KDKFAKSrpiirRFLG 95
                          90       100
                  ....*....|....*....|....*...
gi 966980062 1650 RTEIPVAKIRT-----EQESKGPVTRRL 1672
Cdd:cd08691    96 KLSIPVQRLLErhaigDQELSYTLGRRT 123
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
368-486 4.11e-03

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 42.03  E-value: 4.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  368 KANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEkRLEKQRELerqreeerrkeierr 447
Cdd:PTZ00266  432 KDHAERARIEKENAHRKALEMKILEKKRIERLEREERERLERERMERIERERLERE-RLERERLE--------------- 495
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 966980062  448 eaaKQELERQR--RLEWERIRRQEllnqknREQEEIVRLNS 486
Cdd:PTZ00266  496 ---RDRLERDRldRLERERVDRLE------RDRLEKARRNS 527
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
987-1037 4.34e-03

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212805 [Multi-domain]  Cd Length: 56  Bit Score: 36.79  E-value: 4.34e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  987 IALYPYSSVEPGDLTFTEGEEILVTQKDGEWWTG-SIGDRS--GIFPSNYVKPK 1037
Cdd:cd11872     3 VAIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGfSLRNKSlkGIFPKSYVHIK 56
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
902-953 4.37e-03

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 37.01  E-value: 4.37e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 966980062  902 KAQALCSWTAKKD--NHLNFSKHDIITVLEQQENWWFGEVHGGR-GWFPKSYVKI 953
Cdd:cd11855     1 RARALYPYDASPDdpNELSFEKGEILEVSDTSGKWWQARKSNGEtGICPSNYLQL 55
SH3_CASS4 cd12000
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ...
763-811 4.40e-03

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212933  Cd Length: 57  Bit Score: 37.17  E-value: 4.40e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTI-GEPGWLYGSFQGNFGWFPCN 811
Cdd:cd12000     4 RALYDNKADCSDELAFRRGDILTVLEQNVpGSEGWWKCLLHGRQGLAPAN 53
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
988-1033 4.40e-03

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 36.69  E-value: 4.40e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEIL-VTQKDGEWWTGSIGDRSGIFPSNY 1033
Cdd:cd11818     4 ALYDFTGENEDELSFKAGDIITeLESIDEEWMSGELRGKSGIFPKNF 50
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
904-953 4.52e-03

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 37.11  E-value: 4.52e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQ---QENWWFGEVHGGRGWFPKSYVKI 953
Cdd:cd12056     5 KALFHYEGTNEDELDFKEGEIILIISKdtgEPGWWKGELNGKEGVFPDNFVSQ 57
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1547-1688 4.53e-03

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 42.05  E-value: 4.53e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1547 IDTEKKKREKAYqarsqKTSGIGRLMVHVIEATELKACKPNGKSNPYCEISMGSQS-YTTRTIQDTLNPKWNfncQFFIK 1625
Cdd:COG5038   694 IYNAGGSSSKTV-----YDTPIGAIRVSVRKANDLRNEIPGGKSDPYATVLVNNLVkYRTIYGSSTLNPIWN---EILYV 765
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966980062 1626 DLYQDVLCLTLFDRD--QFSPDDFLGRTEIPVAKIRTEQE---------SKGPVTRRLLLHEVPTGEVWVRFDL 1688
Cdd:COG5038   766 PVTSKNQRLTLECMDyeESGDDRNLGEVNINVSNVSKKDEdsalmetidGAEETGKLSLTGKKVKGTITYKCRF 839
SH3_p40phox cd11869
Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil ...
902-954 4.56e-03

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212802  Cd Length: 54  Bit Score: 37.09  E-value: 4.56e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 954
Cdd:cd11869     1 RAEALFDFTGNSKLELNFKAGDVIFLLSRvNKDWLEGTVRGATGIFPLSFVKII 54
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
1064-1114 4.73e-03

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 36.99  E-value: 4.73e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGelqaRGKKRQKGWFPASHVKL 1114
Cdd:cd11960     8 YQAADDTEISFDPGDIITDIEQIDEGWWRG----TGPDGTYGLFPANYVEL 54
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
762-813 4.78e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 36.64  E-value: 4.78e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd11866     2 YMGLWDCSGNEPDELSFKRGDLIYIISKEYDSFGWWVGELNGKVGLVPKDYL 53
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
1558-1656 5.04e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 38.78  E-value: 5.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062 1558 YQARSQktsgigRLMVHVIEATELKACKPNGK-SNPYCEIS------MGSQSYTTRtiqDTLNPkwNFNCQFFIKDLYQD 1630
Cdd:cd08390     9 YDLEEE------QLTVSLIKARNLPPRTKDVAhCDPFVKVCllpderRSLQSKVKR---KTQNP--NFDETFVFQVSFKE 77
                          90       100       110
                  ....*....|....*....|....*....|
gi 966980062 1631 V----LCLTLFDRDQFSPDDFLGRTEIPVA 1656
Cdd:cd08390    78 LqrrtLRLSVYDVDRFSRHCIIGHVLFPLK 107
CCDC50_N pfam15295
Coiled-coil domain-containing protein 50 N-terminus;
653-740 5.05e-03

Coiled-coil domain-containing protein 50 N-terminus;


Pssm-ID: 464621 [Multi-domain]  Cd Length: 126  Bit Score: 38.94  E-value: 5.05e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   653 TCNTQ--QLALEQLYKIKRDKLKEIERKRLELIQ-KKKLEDEAARKAKQGKENLwkenLRREEEEKQKRLQEEKTQEKIQ 729
Cdd:pfam15295   40 ATNIQrnQLVQNDIRVAKQLQEEEELQAQTLFQRrLAQLEEQDEEIAKEIQEEL----QREAEERRRREEEDEEIARQLQ 115
                           90
                   ....*....|.
gi 966980062   730 EEERKAEEKQR 740
Cdd:pfam15295  116 ERERERERRRK 126
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
904-952 5.13e-03

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 36.52  E-value: 5.13e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGR-GWFPKSYVK 952
Cdd:cd11849     3 RALYDFKSAEPNTLSFSEGETFLLLERsNAHWWLVTNHSGEtGYVPANYVK 53
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
762-814 5.13e-03

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 36.52  E-value: 5.13e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVE 814
Cdd:cd11849     2 YRALYDFKSAEPNTLSFSEGETFLLLERS-NAHWWLVTNHSGETGYVPANYVK 53
SH3_p47phox_1 cd12021
First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called ...
904-952 5.26e-03

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212954 [Multi-domain]  Cd Length: 53  Bit Score: 36.86  E-value: 5.26e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 952
Cdd:cd12021     3 RAIADYEKSSKSEMALKTGDVVEVVEKSENgWWFCQLKAKRGWVPASYLE 52
SH3_SH3RF2_3 cd11784
Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
762-813 5.41e-03

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212718  Cd Length: 55  Bit Score: 36.68  E-value: 5.41e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYV 813
Cdd:cd11784     2 CVALHSYSAHRPEELELQKGEGVRVLGKF--QEGWLRGLslVTGRVGIFPSNYV 53
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
762-813 5.47e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212978  Cd Length: 53  Bit Score: 36.80  E-value: 5.47e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd12045     2 YQGLWDCTGDQPDELSFKRGDTIYILSKEYNRFGWWVGEMKGTIGLVPKAYI 53
SH3_Sorbs2_3 cd11917
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), ...
981-1035 5.76e-03

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212850 [Multi-domain]  Cd Length: 61  Bit Score: 36.89  E-value: 5.76e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966980062  981 SVGEEYIALYPYSSVEPGDLTFTEGEEILVTQK-DGEWWTGSiGDRS---GIFPSNYVK 1035
Cdd:cd11917     2 GGGEPFQALYNYMPRNEDELELREGDVIDVMEKcDDGWFVGT-SRRTkffGTFPGNYVK 59
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
249-311 5.77e-03

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 39.51  E-value: 5.77e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062  249 RQKFNSLDKSMSGYLSGFQARNALLQSNL--SQTQLATIWTLADIDGDGQLKAEEFiLAMH--LTDM 311
Cdd:cd16185     3 RQWFRAVDRDRSGSIDVNELQKALAGGGLlfSLATAEKLIRMFDRDGNGTIDFEEF-AALHqfLSNM 68
tolA PRK09510
cell envelope integrity inner membrane protein TolA; Provisional
367-429 5.78e-03

cell envelope integrity inner membrane protein TolA; Provisional


Pssm-ID: 236545 [Multi-domain]  Cd Length: 387  Bit Score: 40.95  E-value: 5.78e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966980062  367 RKANYERGNMELEKRRQALVEQQQREAERKAQKEKEewerKQRE-----LQEQEWKKQLELEKRLEKQ 429
Cdd:PRK09510   66 RQQQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEQE----RLKQlekerLAAQEQKKQAEEAAKQAAL 129
SH3_ARHGEF9 cd11975
Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also ...
1058-1114 5.84e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212908  Cd Length: 62  Bit Score: 37.00  E-value: 5.84e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGELQargkkRQKGWFPASHVKL 1114
Cdd:cd11975     7 AEAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQID-----DEEGWFPASFVRL 58
PRK00409 PRK00409
recombination and DNA strand exchange inhibitor protein; Reviewed
656-751 5.87e-03

recombination and DNA strand exchange inhibitor protein; Reviewed


Pssm-ID: 234750 [Multi-domain]  Cd Length: 782  Bit Score: 41.35  E-value: 5.87e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  656 TQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKE---NLRREEEEKQKRLQEEKTQEKIQEEE 732
Cdd:PRK00409  527 ELERELEQKAEEAEALLKEAEKLKEELEEKKEKLQEEEDKLLEEAEKEAQQaikEAKKEADEIIKELRQLQKGGYASVKA 606
                          90
                  ....*....|....*....
gi 966980062  733 RKAEEKQRKDKDTLKVEEK 751
Cdd:PRK00409  607 HELIEARKRLNKANEKKEK 625
PRK12585 PRK12585
putative monovalent cation/H+ antiporter subunit G; Reviewed
662-757 5.88e-03

putative monovalent cation/H+ antiporter subunit G; Reviewed


Pssm-ID: 183610  Cd Length: 197  Bit Score: 40.05  E-value: 5.88e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  662 EQLYKIKRDklkEIERKRLELIQKKKLEdeaarKAKQGKENLWKenlRREEEEKQKRLQEEKTQEKIQ-EEERKAEEKQR 740
Cdd:PRK12585  105 DQLRSVKKD---DIKKKKSLIIRQEQIE-----KARQEREELEE---RMEWERREEKIDEREDQEEQErEREEQTIEEQS 173
                          90
                  ....*....|....*..
gi 966980062  741 KDKDTLKVEEKQRETAS 757
Cdd:PRK12585  174 DDSEHEIIEQDESETES 190
SH3_DNMBP_N4 cd11797
Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
1132-1180 5.93e-03

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212731  Cd Length: 50  Bit Score: 36.63  E-value: 5.93e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1132 VIAMYDYAANNEDELSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNY 1180
Cdd:cd11797     2 GVALYRFQALEPNELDFEVGDRIRIIATLEDGWLEGELKGRRGIFPHRF 50
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
902-954 5.93e-03

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212724 [Multi-domain]  Cd Length: 64  Bit Score: 36.92  E-value: 5.93e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVL------EQQENWWFG--EVHGGRGWFPKSYVKII 954
Cdd:cd11790     4 KVRATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGvkESTGCRGVFPENFTERI 64
SH3_Tks_1 cd12015
First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
762-815 6.23e-03

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212948  Cd Length: 53  Bit Score: 36.63  E-value: 6.23e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 815
Cdd:cd12015     2 YVVVADYKKQQPNEISLRAGDVVDVIEKN--ENGWWFVSLEDEQGWVPATYLEP 53
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
657-754 6.30e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 40.67  E-value: 6.30e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   657 QQLALEQLYKIKRDKLKEIERK-RLELIQKKKLEDEAARKAKQGKenlwKENLRRE--EEEKQKRLQEEKTQEKIQEEER 733
Cdd:pfam13868   80 EQIEEREQKRQEEYEEKLQEREqMDEIVERIQEEDQAEAEEKLEK----QRQLREEidEFNEEQAEWKELEKEEEREEDE 155
                           90       100
                   ....*....|....*....|..
gi 966980062   734 KAEEKQR-KDKDTLKVEEKQRE 754
Cdd:pfam13868  156 RILEYLKeKAEREEEREAEREE 177
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
1058-1114 6.46e-03

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 36.31  E-value: 6.46e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 966980062 1058 AQVTSAYVASGSEQLSLAPGQLILILKKNTSGWWQGElqarGKKRQKGWFPASHVKL 1114
Cdd:cd11962     2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGT----NSKGESGLFPSNYVEL 54
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
763-814 6.70e-03

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212747  Cd Length: 53  Bit Score: 36.32  E-value: 6.70e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  763 RALYPFEARNHDEMSFNSGDIIQVDEKTiGEPGWLyGSFQGNFGWFPCNYVE 814
Cdd:cd11813     3 KALLDFERHDDDELGFRKNDIITIISQK-DEHCWV-GELNGLRGWFPAKFVE 52
SH3_BAIAP2L1 cd11913
Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, ...
1067-1114 6.85e-03

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212846  Cd Length: 58  Bit Score: 36.43  E-value: 6.85e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 966980062 1067 SGSEQLSLAPGQ-LILILKKNTSGWWQGELQARGkkrQKGWFPASHVKL 1114
Cdd:cd11913    13 NNKTLLSFAQGDvITLLIPEEKDGWLYGEHDTTK---ARGWFPSSYTRP 58
PTZ00184 PTZ00184
calmodulin; Provisional
247-306 6.88e-03

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 38.97  E-value: 6.88e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966980062  247 KYRQKFNSLDKSMSGYLSGFQARNAL--LQSNLSQTQLATIWTLADIDGDGQLKAEEFILAM 306
Cdd:PTZ00184   85 EIKEAFKVFDRDGNGFISAAELRHVMtnLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
SH3_SNX33 cd11896
Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome ...
1134-1183 6.99e-03

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212829 [Multi-domain]  Cd Length: 55  Bit Score: 36.48  E-value: 6.99e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1134 AMYDYAANNEDELSFSKGQLINVMNKDDPD-WWQGEIN-GVTGLFPSNYVKM 1183
Cdd:cd11896     4 ALYSFQSENKEEINIQENEELVIFSENSLDgWLQGQNSrGETGLFPASYVEI 55
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
902-951 7.06e-03

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 36.23  E-value: 7.06e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 951
Cdd:cd11816     1 RCVARFDFEGEQEDELSFSEGDVITLKEYvGEEWAKGELNGKIGIFPLNFV 51
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
762-813 7.06e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 36.37  E-value: 7.06e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 813
Cdd:cd12044     2 YQGLWDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDYL 53
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
903-952 7.07e-03

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212910 [Multi-domain]  Cd Length: 58  Bit Score: 36.53  E-value: 7.07e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQ---QENWWFGEVHGGRGWFPKSYVK 952
Cdd:cd11977     3 AVARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYVE 55
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
984-1034 7.09e-03

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 36.19  E-value: 7.09e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  984 EEYIALYPYSSVEPGDLTFTEGEEILVTQKDGE-WWTG--SIGdRSGIFPSNYV 1034
Cdd:cd11758     1 EYVRALFDFPGNDDEDLPFKKGEILTVIRKPEEqWWNArnSEG-KTGMIPVPYV 53
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
335-759 7.18e-03

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 40.91  E-value: 7.18e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  335 KQIDSINGTLPSYQKIQEEEPQKKLPVtfEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQ 414
Cdd:COG4717    56 DELFKPQGRKPELNLKELKELEEELKE--AEEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQE 133
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  415 EWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRL-EWERIRRQELLNQKNREQEEIVRLNSKKKSLHL 493
Cdd:COG4717   134 LEALEAELAELPERLEELEERLEELRELEEELEELEAELAELQEELeELLEQLSLATEEELQDLAEELEELQQRLAELEE 213
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  494 ELEALNGKHQQISGRLQDVRLKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNERI-------- 565
Cdd:COG4717   214 ELEEAQEELEELEEELEQLENELEAAALEERLKEARLLLLIAAALLALLGLGGSLLSLILTIAGVLFLVLGLlallflll 293
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  566 --KNMQFSNTPDSGVSLLHKKSLEKQELCQRLKEQ---LDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLsllscl 640
Cdd:COG4717   294 arEKASLGKEAEELQALPALEELEEEELEELLAALglpPDLSPEELLELLDRIEELQELLREAEELEEELQLEE------ 367
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  641 nnlflLLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQ 720
Cdd:COG4717   368 -----LEQEIAALLAEAGVEDEEELRAALEQAEEYQELKEELEELEEQLEELLGELEELLEALDEEELEEELEELEEELE 442
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|
gi 966980062  721 E-EKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASVL 759
Cdd:COG4717   443 ElEEELEELREELAELEAELEQLEEDGELAELLQELEELK 482
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
904-951 7.20e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 36.37  E-value: 7.20e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062  904 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 951
Cdd:cd12044     3 QGLWDCFGDNPDELSFQRGDLIYILSKEYNmygWWVGELNGIVGIVPKDYL 53
ERM_helical pfam20492
Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related ...
372-484 7.21e-03

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.


Pssm-ID: 466641 [Multi-domain]  Cd Length: 120  Bit Score: 38.36  E-value: 7.21e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   372 ERGNMELEKRRQALVEQQqreaeRKAQKEKEEWERKQRELQEQewKKQLELEK-RLEKQRELERQREEERRKEIERREAA 450
Cdd:pfam20492    5 EREKQELEERLKQYEEET-----KKAQEELEESEETAEELEEE--RRQAEEEAeRLEQKRQEAEEEKERLEESAEMEAEE 77
                           90       100       110
                   ....*....|....*....|....*....|....
gi 966980062   451 KQELERQRRLEWERIRRQEllNQKNREQEEIVRL 484
Cdd:pfam20492   78 KEQLEAELAEAQEEIARLE--EEVERKEEEARRL 109
SMC_N pfam02463
RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...
348-761 7.55e-03

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.


Pssm-ID: 426784 [Multi-domain]  Cd Length: 1161  Bit Score: 41.11  E-value: 7.55e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   348 QKIQEEEPQKKLPVTFEDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLE 427
Cdd:pfam02463  440 ELKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQEQLELLLSRQKLEERSQKESKARSGLKVLLALIKDG 519
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   428 KQRELERQREEERRK---------------EIERREAAKQELERQRRLEWERIRRQELLNQKNREQEEIVRLNSKKKSLH 492
Cdd:pfam02463  520 VGGRIISAHGRLGDLgvavenykvaistavIVEVSATADEVEERQKLVRALTELPLGARKLRLLIPKLKLPLKSIAVLEI 599
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   493 LELEALNGKHQQISGRLQDVR--------LKKQTQKTELEVLDKQCDLEIMEIKQLQQELQEYQNKLIYLVPEKQLLNER 564
Cdd:pfam02463  600 DPILNLAQLDKATLEADEDDKrakvvegiLKDTELTKLKESAKAKESGLRKGVSLEEGLAEKSEVKASLSELTKELLEIQ 679
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   565 IKNMQFSNTPDSGVSLLHKKSLEKQELCQRLKEQ---LDALEKETASKLSEMDSYNNQLKCGNMDDSVLQCLLSLLSCLn 641
Cdd:pfam02463  680 ELQEKAESELAKEEILRRQLEIKKKEQREKEELKklkLEAEELLADRVQEAQDKINEELKLLKQKIDEEEEEEEKSRLK- 758
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   642 nlfLLLKELRETCNTQQLALEQLYKIKRDKLKEIERKRLeliQKKKLEDEAARKAKQGKENLWKENLRREEEEKQKRLQE 721
Cdd:pfam02463  759 ---KEEKEEEKSELSLKEKELAEEREKTEKLKVEEEKEE---KLKAQEEELRALEEELKEEAELLEEEQLLIEQEEKIKE 832
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|
gi 966980062   722 EKTQEKIQEEERKAEEKQRKDKDTLKVEEKQRETASVLVN 761
Cdd:pfam02463  833 EELEELALELKEEQKLEKLAEEELERLEEEITKEELLQEL 872
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
364-483 7.69e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 40.67  E-value: 7.69e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   364 EDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEwERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKE 443
Cdd:pfam13868  140 AEWKELEKEEEREEDERILEYLKEKAEREEEREAEREEIE-EEKEREIARLRAQQEKAQDEKAERDELRAKLYQEEQERK 218
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 966980062   444 IERREAAKQELERQRRLEWERIRRQELLNQKNREQEEIVR 483
Cdd:pfam13868  219 ERQKEREEAEKKARQRQELQQAREEQIELKERRLAEEAER 258
DUF5401 pfam17380
Family of unknown function (DUF5401); This is a family of unknown function found in ...
656-758 7.88e-03

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.


Pssm-ID: 375164 [Multi-domain]  Cd Length: 722  Bit Score: 40.88  E-value: 7.88e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   656 TQQLALEQLYKIKRDKLKEIERKrleliQKKKLEDEAARKAKQGKENLWKENLRR---EEEEKQKRLQEEKTQEKIQEEE 732
Cdd:pfam17380  266 TENEFLNQLLHIVQHQKAVSERQ-----QQEKFEKMEQERLRQEKEEKAREVERRrklEEAEKARQAEMDRQAAIYAEQE 340
                           90       100
                   ....*....|....*....|....*.
gi 966980062   733 RKAEEKQRkDKDTLKVEEKQRETASV 758
Cdd:pfam17380  341 RMAMERER-ELERIRQEERKRELERI 365
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
902-956 7.96e-03

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 36.53  E-value: 7.96e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWF-GEVHGGRGWFPKSYVKIIPG 956
Cdd:cd11972     4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYeGVMNGVTGLFPGNYVESIMH 59
ClpA COG0542
ATP-dependent Clp protease, ATP-binding subunit ClpA [Posttranslational modification, protein ...
372-469 8.07e-03

ATP-dependent Clp protease, ATP-binding subunit ClpA [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440308 [Multi-domain]  Cd Length: 836  Bit Score: 40.84  E-value: 8.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062  372 ERGNMELEKRRQALV-EQQQREAERKAQKEKEEWE-RKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREA 449
Cdd:COG0542   417 ERRLEQLEIEKEALKkEQDEASFERLAELRDELAElEEELEALKARWEAEKELIEEIQELKEELEQRYGKIPELEKELAE 496
                          90       100
                  ....*....|....*....|
gi 966980062  450 AKQELERQRRLEWERIRRQE 469
Cdd:COG0542   497 LEEELAELAPLLREEVTEED 516
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
762-813 8.16e-03

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212858  Cd Length: 57  Bit Score: 36.13  E-value: 8.16e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  762 YRALYPFEARNHDEMSFNSGDIIQVDEKTigEPGWLYGSF--QGNFGWFPCNYV 813
Cdd:cd11925     3 YLALYAYKPQKNDELELRKGEMYRVIEKC--QDGWFKGTSlrTGVSGVFPGNYV 54
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
988-1035 8.20e-03

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212778  Cd Length: 56  Bit Score: 36.17  E-value: 8.20e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062  988 ALYPYSSVEPGDLTFTEGEEILVTQKDGE----WWTGSIGDRSGIFPSNYVK 1035
Cdd:cd11844     4 ALYDNVAESPDELAFRRGDILTVLEQNTAglegWWLCSLRGRQGIAPGNRLK 55
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
657-754 8.32e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 40.29  E-value: 8.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   657 QQLALEQLYKIKRdklKEIERKRLELIQK--KKLEDEAARKAKQgkENLWKENLRREEEEKQKRLQEEKTQEKIQEEE-- 732
Cdd:pfam13868  163 EKAEREEEREAER---EEIEEEKEREIARlrAQQEKAQDEKAER--DELRAKLYQEEQERKERQKEREEAEKKARQRQel 237
                           90       100
                   ....*....|....*....|..
gi 966980062   733 RKAEEKQRKDKDTLKVEEKQRE 754
Cdd:pfam13868  238 QQAREEQIELKERRLAEEAERE 259
SH3_SH3RF3_2 cd11931
Second Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
1134-1181 8.42e-03

Second Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212864  Cd Length: 55  Bit Score: 36.05  E-value: 8.42e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 966980062 1134 AMYDYAANNEDE----LSFSKGQLINVMNKDDPDWWQGEINGVTGLFPSNYV 1181
Cdd:cd11931     4 ALYDFEIKDKDQdkdcLTFTKDEILTVIRRVDENWAEGMLGDKIGIFPILYV 55
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
902-954 8.57e-03

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212854  Cd Length: 55  Bit Score: 36.05  E-value: 8.57e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966980062  902 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 954
Cdd:cd11921     2 AARLKFDFQAQSPKELTLQKGDIVYIHKEvDKNWLEGEHHGRVGIFPANYVEVL 55
CCDC66 pfam15236
Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil ...
348-425 8.67e-03

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.


Pssm-ID: 434558 [Multi-domain]  Cd Length: 154  Bit Score: 38.62  E-value: 8.67e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   348 QKIQEEEPQKKLpvtfEDKRKANyERGNMELEKRRQALVEQQQREAERKAQKEKEE-WERKQRELQE-----QEWKKQLE 421
Cdd:pfam15236   63 KQLEEKERQKKL----EEERRRQ-EEQEEEERLRREREEEQKQFEEERRKQKEKEEaMTRKTQALLQamqkaQELAQRLK 137

                   ....
gi 966980062   422 LEKR 425
Cdd:pfam15236  138 QEQR 141
SH3_Noxa1_C cd12047
C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox ...
905-951 8.67e-03

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212980  Cd Length: 53  Bit Score: 35.95  E-value: 8.67e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 966980062  905 ALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGGRGWFPKSYV 951
Cdd:cd12047     4 AQHDYSAQGPEDLEFSQGDTIDILsEVNQEWLEGHCDGRIGIFPKCFA 51
CAF-1_p150 pfam11600
Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide ...
366-429 8.69e-03

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.


Pssm-ID: 402959 [Multi-domain]  Cd Length: 164  Bit Score: 38.90  E-value: 8.69e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966980062   366 KRKANYERGNMELEKRRQALVEQQQREAERKAQKEKEEWER--KQRELQEQEWKKQLELEKRLEKQ 429
Cdd:pfam11600   42 KEEAKAEKERAKEEARRKKEEEKELKEKERREKKEKDEKEKaeKLRLKEEKRKEKQEALEAKLEEK 107
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
903-951 8.91e-03

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212743 [Multi-domain]  Cd Length: 53  Bit Score: 36.23  E-value: 8.91e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 966980062  903 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 951
Cdd:cd11809     2 ATAQFDYTGRSERELSFKKGDSLTLYRQVSDdWWRGQLNGQDGLVPHKYI 51
DUF4670 pfam15709
Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins ...
648-753 8.91e-03

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.


Pssm-ID: 464815 [Multi-domain]  Cd Length: 522  Bit Score: 40.71  E-value: 8.91e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   648 KELRETCNTQQLALEQLYKIKRDKLKEIERKRLELIQKKKLEDEAARkakqgkenlwkENLRREEEEKQKRLQEEKTQEK 727
Cdd:pfam15709  372 EKMREELELEQQRRFEEIRLRKQRLEEERQRQEEEERKQRLQLQAAQ-----------ERARQQQEEFRRKLQELQRKKQ 440
                           90       100
                   ....*....|....*....|....*.
gi 966980062   728 IQEEERKAEEKQRKDKDTLKVEEKQR 753
Cdd:pfam15709  441 QEEAERAEAEKQRQKELEMQLAEEQK 466
SH3_DOCK1_5_A cd12051
Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called ...
1064-1114 9.00e-03

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212984 [Multi-domain]  Cd Length: 56  Bit Score: 35.95  E-value: 9.00e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKkNTSGWWQGelQARGKKRQKGWFPASHVKL 1114
Cdd:cd12051     8 YDARGPDELSLQIGDTVHILE-TYEGWYRG--YTLRKKSKKGIFPASYIHL 55
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
364-520 9.00e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 40.29  E-value: 9.00e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   364 EDKRKANYERGNMELEKRRQALVEQQQREAERKAQKEK-------EEWERK--QRELQEQEWKKQLELE----KRLEKQR 430
Cdd:pfam13868  168 EEEREAEREEIEEEKEREIARLRAQQEKAQDEKAERDElraklyqEEQERKerQKEREEAEKKARQRQElqqaREEQIEL 247
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966980062   431 ELERQREEERR--KEIERREAAKQELERQRRLEWERIRRQELlnQKNREQEEIVRLNSKKKSLHLELEALNGKHQQISGR 508
Cdd:pfam13868  248 KERRLAEEAEReeEEFERMLRKQAEDEEIEQEEAEKRRMKRL--EHRRELEKQIEEREEQRAAEREEELEEGERLREEEA 325
                          170
                   ....*....|..
gi 966980062   509 LQDVRLKKQTQK 520
Cdd:pfam13868  326 ERRERIEEERQK 337
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
1064-1114 9.25e-03

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 35.86  E-value: 9.25e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 966980062 1064 YVASGSEQLSLAPGQLILILKKNTSGWWQGElqARGkkrQKGWFPASHVKL 1114
Cdd:cd11959     8 YQAADDDEISFDPDDIITNIEMIDEGWWRGV--CRG---KYGLFPANYVEL 53
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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