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Conserved domains on  [gi|1039767156|ref|XP_017175587|]
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rho guanine nucleotide exchange factor 19 isoform X1 [Mus musculus]

Protein Classification

RhoGEF family protein; PH domain-containing RhoGEF family protein( domain architecture ID 10457350)

RhoGEF (rho guanine nucleotide exchange factor) family protein similar to RhoGEF and PH (pleckstrin homology) domain regions of vertebrate RhoGEFs that accelerate the intrinsic exchange activity of Rho GTPases to stimulate formation of Rho-GTP| PH domain-containing RhoGEF family protein may function as a guanine nucleotide exchange factor; similar to Homo sapiens pleckstrin homology domain-containing family G member 4B and Danio rerio quattro

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
382-558 6.76e-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: 156.31  E-value: 6.76e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 382 FELITSEASYIHSLSVAVGHFLGSVE--LSECLgtQDKQWLFSKLPEVKSTSERFLhdLEQRLEADVLRFSVCDVVLHHC 459
Cdd:pfam00621   3 KELLQTERSYVRDLEILVEVFLPPNSkpLSESE--EEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 460 PAFRrVYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKMLVENILKRTAPGSQD 539
Cdd:pfam00621  79 PGFK-VYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPD 157
                         170
                  ....*....|....*....
gi 1039767156 540 EDMATKAFSALKELVQECN 558
Cdd:pfam00621 158 YEDLKKALEAIKEVAKQIN 176
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
580-706 8.21e-41

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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: 269929  Cd Length: 131  Bit Score: 145.86  E-value: 8.21e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 580 EGKIFPLISQARWLVRHGELVELAPLPAAPPAKLKLSSKAVYLHLFNDCLLLSRRKELGKFAVFVHANMAELQVRDLSLK 659
Cdd:cd01221     1 KIKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVEDP 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039767156 660 LQGIPG---HVFLLRLLHGQRAR-HQLLLRARTESEKQRWISALRPSSPQE 706
Cdd:cd01221    81 LQLPQPlgkNLFLLTLLENHEGKtVELLLSAESESDRERWLSALSPPKSEL 131
SH3 super family cl17036
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
719-773 1.13e-26

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.


The actual alignment was detected with superfamily member cd11940:

Pssm-ID: 473055  Cd Length: 55  Bit Score: 102.95  E-value: 1.13e-26
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11940     1 QVQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRLSDGERGWFPQSHVEE 55
 
Name Accession Description Interval E-value
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
382-558 6.76e-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: 156.31  E-value: 6.76e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 382 FELITSEASYIHSLSVAVGHFLGSVE--LSECLgtQDKQWLFSKLPEVKSTSERFLhdLEQRLEADVLRFSVCDVVLHHC 459
Cdd:pfam00621   3 KELLQTERSYVRDLEILVEVFLPPNSkpLSESE--EEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 460 PAFRrVYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKMLVENILKRTAPGSQD 539
Cdd:pfam00621  79 PGFK-VYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPD 157
                         170
                  ....*....|....*....
gi 1039767156 540 EDMATKAFSALKELVQECN 558
Cdd:pfam00621 158 YEDLKKALEAIKEVAKQIN 176
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
580-706 8.21e-41

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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: 269929  Cd Length: 131  Bit Score: 145.86  E-value: 8.21e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 580 EGKIFPLISQARWLVRHGELVELAPLPAAPPAKLKLSSKAVYLHLFNDCLLLSRRKELGKFAVFVHANMAELQVRDLSLK 659
Cdd:cd01221     1 KIKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVEDP 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039767156 660 LQGIPG---HVFLLRLLHGQRAR-HQLLLRARTESEKQRWISALRPSSPQE 706
Cdd:cd01221    81 LQLPQPlgkNLFLLTLLENHEGKtVELLLSAESESDRERWLSALSPPKSEL 131
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
377-558 8.23e-39

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: 142.05  E-value: 8.23e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 377 LQEAKFELITSEASYIHSLSVAVGHFLGS-VELSECLGTQDKQWLFSKLPEVKSTSERFLHDLEQRLEADVLR-FSVCDV 454
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPlDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSgPRIGDV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 455 VLHHCPAFRrVYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESpvCQRLPLTSFLILPFQRVTRLKMLVENILKRTA 534
Cdd:cd00160    81 FLKLAPFFK-IYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                         170       180
                  ....*....|....*....|....
gi 1039767156 535 PGSQDEDMATKAFSALKELVQECN 558
Cdd:cd00160   158 DGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
382-559 1.84e-37

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: 138.20  E-value: 1.84e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  382 FELITSEASYIHSLSVAVGHFLGSVELSECLGTQDK-QWLFSKLPEVKSTSERFLHDLEQRL-EADVLRFSVCDVVLHHC 459
Cdd:smart00325   3 KELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNElETLFGNIEEIYEFHRDFLDELEERIeEWDDSVERIGDVFLKLE 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  460 PAFRrVYLPYVTNQAYQERTYQRLLlENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKMLVENILKRTAPGSQD 539
Cdd:smart00325  83 EFFK-IYSEYCSNHPDALELLKKLK-KNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160
                          170       180
                   ....*....|....*....|
gi 1039767156  540 EDMATKAFSALKELVQECNA 559
Cdd:smart00325 161 REDLKKALKAIKELANQVNE 180
SH3_ARHGEF5_19 cd11940
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ...
719-773 1.13e-26

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: 102.95  E-value: 1.13e-26
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11940     1 QVQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRLSDGERGWFPQSHVEE 55
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
370-579 1.64e-13

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 74.54  E-value: 1.64e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  370 LSLRDCKLQEAKFELITSEASYIHSLSVAVGHFLGSVELSECLGTQDKQ----WLFSKLPEVKSTSERFLHDLEQRLEAD 445
Cdd:COG5422    478 LPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARRnfikHVFANINEIYAVNSKLLKALTNRQCLS 557
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  446 VLRFSVCDVVLHHCPAFRRvYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKML 525
Cdd:COG5422    558 PIVNGIADIFLDYVPKFEP-FIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLL 636
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1039767156  526 VENILKRTAPGSQDEDMATKAFSALKELVQECNASVQSMKRTEELIHLSKKIHF 579
Cdd:COG5422    637 LEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLF 690
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
716-771 8.10e-10

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: 55.24  E-value: 8.10e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039767156  716 DRPQVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGvRLADGEKGWVPQAHV 771
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKG-RLGRGKEGLFPSNYV 55
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
618-700 6.84e-07

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 48.31  E-value: 6.84e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  618 KAVYLHLFNDCLLLSRRKELGKFAVFVHA-NMAELQVRDLSLKLQGIPGHVFLLRLlhgqRARHQLLLRARTESEKQRWI 696
Cdd:smart00233  19 KKRYFVLFNSTLLYYKSKKDKKSYKPKGSiDLSGCTVREAPDPDSSKKPHCFEIKT----SDRKTLLLQAESEEEREKWV 94

                   ....
gi 1039767156  697 SALR 700
Cdd:smart00233  95 EALR 98
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
720-774 8.55e-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: 46.44  E-value: 8.55e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 720 VQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLadGEKGWVPQAHVVEI 774
Cdd:pfam07653   2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETG--GRVGLVPSTAVEEI 54
PH pfam00169
PH domain; PH stands for pleckstrin homology.
593-700 3.77e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 3.77e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 593 LVRHGELVELAPLPAAppaklklSSKAVYLHLFNDCLLLSRRKELGKFAVFVHA-NMAELQVRDLSLKLQGIPGHVFLLR 671
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK-------SWKKRYFVLFDGSLLYYKDDKSGKSKEPKGSiSLSGCEVVEVVASDSPKRKFCFELR 73
                          90       100
                  ....*....|....*....|....*....
gi 1039767156 672 LLHGQRARhQLLLRARTESEKQRWISALR 700
Cdd:pfam00169  74 TGERTGKR-TYLLQAESEEERKDWIKAIQ 101
 
Name Accession Description Interval E-value
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
382-558 6.76e-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: 156.31  E-value: 6.76e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 382 FELITSEASYIHSLSVAVGHFLGSVE--LSECLgtQDKQWLFSKLPEVKSTSERFLhdLEQRLEADVLRFSVCDVVLHHC 459
Cdd:pfam00621   3 KELLQTERSYVRDLEILVEVFLPPNSkpLSESE--EEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 460 PAFRrVYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKMLVENILKRTAPGSQD 539
Cdd:pfam00621  79 PGFK-VYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPD 157
                         170
                  ....*....|....*....
gi 1039767156 540 EDMATKAFSALKELVQECN 558
Cdd:pfam00621 158 YEDLKKALEAIKEVAKQIN 176
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
580-706 8.21e-41

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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: 269929  Cd Length: 131  Bit Score: 145.86  E-value: 8.21e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 580 EGKIFPLISQARWLVRHGELVELAPLPAAPPAKLKLSSKAVYLHLFNDCLLLSRRKELGKFAVFVHANMAELQVRDLSLK 659
Cdd:cd01221     1 KIKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVEDP 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039767156 660 LQGIPG---HVFLLRLLHGQRAR-HQLLLRARTESEKQRWISALRPSSPQE 706
Cdd:cd01221    81 LQLPQPlgkNLFLLTLLENHEGKtVELLLSAESESDRERWLSALSPPKSEL 131
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
377-558 8.23e-39

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: 142.05  E-value: 8.23e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 377 LQEAKFELITSEASYIHSLSVAVGHFLGS-VELSECLGTQDKQWLFSKLPEVKSTSERFLHDLEQRLEADVLR-FSVCDV 454
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPlDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSgPRIGDV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 455 VLHHCPAFRrVYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESpvCQRLPLTSFLILPFQRVTRLKMLVENILKRTA 534
Cdd:cd00160    81 FLKLAPFFK-IYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                         170       180
                  ....*....|....*....|....
gi 1039767156 535 PGSQDEDMATKAFSALKELVQECN 558
Cdd:cd00160   158 DGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
382-559 1.84e-37

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: 138.20  E-value: 1.84e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  382 FELITSEASYIHSLSVAVGHFLGSVELSECLGTQDK-QWLFSKLPEVKSTSERFLHDLEQRL-EADVLRFSVCDVVLHHC 459
Cdd:smart00325   3 KELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNElETLFGNIEEIYEFHRDFLDELEERIeEWDDSVERIGDVFLKLE 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  460 PAFRrVYLPYVTNQAYQERTYQRLLlENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKMLVENILKRTAPGSQD 539
Cdd:smart00325  83 EFFK-IYSEYCSNHPDALELLKKLK-KNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160
                          170       180
                   ....*....|....*....|
gi 1039767156  540 EDMATKAFSALKELVQECNA 559
Cdd:smart00325 161 REDLKKALKAIKELANQVNE 180
SH3_ARHGEF5_19 cd11940
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ...
719-773 1.13e-26

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: 102.95  E-value: 1.13e-26
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11940     1 QVQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRLSDGERGWFPQSHVEE 55
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
719-773 2.53e-22

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: 90.47  E-value: 2.53e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11793     1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRDGERGWFPSSYTEE 55
SH3_ephexin1 cd11939
Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called ...
719-773 6.19e-17

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: 75.37  E-value: 6.19e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11939     1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGERLHDQERGWFPSSVVEE 55
SH3_ARHGEF16_26 cd11938
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ...
719-767 1.29e-13

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: 66.02  E-value: 1.29e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVP 767
Cdd:cd11938     1 QVEIIKAYTAKQPDELSLQQADVVLVLQTESDGWYYGERLRDGERGWFP 49
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
370-579 1.64e-13

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 74.54  E-value: 1.64e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  370 LSLRDCKLQEAKFELITSEASYIHSLSVAVGHFLGSVELSECLGTQDKQ----WLFSKLPEVKSTSERFLHDLEQRLEAD 445
Cdd:COG5422    478 LPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARRnfikHVFANINEIYAVNSKLLKALTNRQCLS 557
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  446 VLRFSVCDVVLHHCPAFRRvYLPYVTNQAYQERTYQRLLLENPKFPGILARLEESPVCQRLPLTSFLILPFQRVTRLKML 525
Cdd:COG5422    558 PIVNGIADIFLDYVPKFEP-FIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLL 636
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1039767156  526 VENILKRTAPGSQDEDMATKAFSALKELVQECNASVQSMKRTEELIHLSKKIHF 579
Cdd:COG5422    637 LEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLF 690
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
716-771 8.10e-10

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: 55.24  E-value: 8.10e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039767156  716 DRPQVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGvRLADGEKGWVPQAHV 771
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKG-RLGRGKEGLFPSNYV 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
719-770 2.25e-08

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: 50.92  E-value: 2.25e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGvRLADGEKGWVPQAH 770
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEG-ELNGGREGLFPANY 51
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
618-700 6.84e-07

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 48.31  E-value: 6.84e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156  618 KAVYLHLFNDCLLLSRRKELGKFAVFVHA-NMAELQVRDLSLKLQGIPGHVFLLRLlhgqRARHQLLLRARTESEKQRWI 696
Cdd:smart00233  19 KKRYFVLFNSTLLYYKSKKDKKSYKPKGSiDLSGCTVREAPDPDSSKKPHCFEIKT----SDRKTLLLQAESEEEREKWV 94

                   ....
gi 1039767156  697 SALR 700
Cdd:smart00233  95 EALR 98
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
720-774 8.55e-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: 46.44  E-value: 8.55e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 720 VQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLadGEKGWVPQAHVVEI 774
Cdd:pfam07653   2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETG--GRVGLVPSTAVEEI 54
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
725-773 1.15e-06

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: 46.10  E-value: 1.15e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1039767156 725 TYKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHVVE 773
Cdd:cd11766     7 NYEAQREDELSLRKGDRVLVLEKSSDGWWRGE--CNGQVGWFPSNYVTE 53
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
726-767 1.54e-06

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: 45.66  E-value: 1.54e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGvRLADGEKGWVP 767
Cdd:pfam00018   6 YTAQEPDELSFKKGDIIIVLEKSEDGWWKG-RNKGGKEGLIP 46
PH pfam00169
PH domain; PH stands for pleckstrin homology.
593-700 3.77e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 3.77e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767156 593 LVRHGELVELAPLPAAppaklklSSKAVYLHLFNDCLLLSRRKELGKFAVFVHA-NMAELQVRDLSLKLQGIPGHVFLLR 671
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK-------SWKKRYFVLFDGSLLYYKDDKSGKSKEPKGSiSLSGCEVVEVVASDSPKRKFCFELR 73
                          90       100
                  ....*....|....*....|....*....
gi 1039767156 672 LLHGQRARhQLLLRARTESEKQRWISALR 700
Cdd:pfam00169  74 TGERTGKR-TYLLQAESEEERKDWIKAIQ 101
SH3_SH3RF2_3 cd11784
Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
723-772 1.65e-05

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: 42.84  E-value: 1.65e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039767156 723 VRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVV 772
Cdd:cd11784     5 LHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLSLVTGRVGIFPSNYVS 54
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
719-773 4.18e-05

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: 41.53  E-value: 4.18e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHVVE 773
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGT--LNGKTGWFPSNYVKE 53
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
725-771 7.42e-05

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: 7.42e-05
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gi 1039767156 725 TYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHV 771
Cdd:cd11783     7 PYKPQKPDELELRKGEMYTVTEKCQDGWFKGTSLRTGQSGVFPGNYV 53
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
720-771 7.99e-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: 40.77  E-value: 7.99e-05
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gi 1039767156 720 VQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHV 771
Cdd:cd11826     2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGV--LNGVTGLFPGNYV 51
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
726-771 9.58e-05

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: 40.71  E-value: 9.58e-05
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gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHV 771
Cdd:cd11873     8 YDAEEPDELTLKVGDIITNVKKMEEGWWEGT--LNGKRGMFPDNFV 51
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
725-773 2.00e-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: 39.59  E-value: 2.00e-04
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gi 1039767156 725 TYKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHVVE 773
Cdd:cd11772     7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKAT--CGGKTGLIPSNYVEE 53
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
721-771 2.02e-04

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: 40.01  E-value: 2.02e-04
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gi 1039767156 721 QCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEK---GWVPQAHV 771
Cdd:cd11839     3 QVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARGKKrqiGWFPANYV 56
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
726-773 2.08e-04

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: 39.99  E-value: 2.08e-04
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gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRlaDGEKGWVPQAHVVE 773
Cdd:cd11902     9 YVAEREDELSLVKGSRVTVMEKCSDGWWRGSY--NGQIGWFPSNYVVE 54
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
719-771 2.08e-04

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: 39.62  E-value: 2.08e-04
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gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAV-KTRTSDGWLEGVRlADGEKGWVPQAHV 771
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTItRQDVGDGWLEGRN-SRGEVGLFPSSYV 53
SH3_DNMBP_N2 cd11795
Second N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
722-773 3.27e-04

Second 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: 212729  Cd Length: 54  Bit Score: 39.35  E-value: 3.27e-04
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gi 1039767156 722 CVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGvRLADGEKGWVPQAHVVE 773
Cdd:cd11795     4 CIEAFTSQEPGHLNLQRGDLVELTGTTDSGWLQG-RSCWGSSGFFPSSCVQE 54
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
725-773 3.50e-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: 3.50e-04
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gi 1039767156 725 TYKAL------QPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11858     1 TYKALydfagsVANELSLKKDDIVYIVQKEDNGWWLAKKLDESKEGWVPAAYLEE 55
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
720-767 3.72e-04

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: 39.23  E-value: 3.72e-04
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gi 1039767156 720 VQCVRTYKALQPDELTLEKTDILAV-----KTRTSDGWLEGVRLADGEKGWVP 767
Cdd:cd11790     5 VRATHDYTAEDTDELTFEKGDVILVipfddPEEQDEGWLMGVKESTGCRGVFP 57
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
726-771 4.00e-04

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: 39.03  E-value: 4.00e-04
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gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGvRLADGEKGWVPQAHV 771
Cdd:cd11812     8 YTANRSDELTIHRGDIIRVLYKDNDNWWFG-SLVNGQQGYFPANYV 52
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
719-773 4.15e-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: 39.02  E-value: 4.15e-04
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gi 1039767156 719 QVQCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHVVE 773
Cdd:cd12046     1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQ--CKGKIGIFPSAFVED 53
SH3_JIP1 cd11943
Src homology 3 domain of JNK-interacting protein 1; JNK-interacting protein 1 (JIP1) is also ...
730-773 5.10e-04

Src homology 3 domain of JNK-interacting protein 1; JNK-interacting protein 1 (JIP1) is also called Islet-brain 1 (IB1) or Mitogen-activated protein kinase 8-interacting protein 1 (MAPK8IP1). It is highly expressed in neurons, where it functions as an adaptor linking motor to cargo during axonal transport. It also affects microtubule dynamics in neurons. JIP1 is also found in pancreatic beta-cells, where it is involved in regulating insulin secretion. In addition to a JNK binding domain, JIP1 also contains SH3 and Phosphotyrosine-binding (PTB) domains. Its SH3 domain homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212876  Cd Length: 55  Bit Score: 38.81  E-value: 5.10e-04
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gi 1039767156 730 QPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11943    12 HPDELELEVDDPLLVEVQAEDYWYEAYNMRTGARGIFPAYYAIE 55
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
725-773 5.13e-04

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: 38.86  E-value: 5.13e-04
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gi 1039767156 725 TYKALQPDELTLEKTDILAVKTRTSDGWLEGVRlaDGEKGWVPQAHVVE 773
Cdd:cd11901     9 NYTAEREDELSLVKGTKVIVMEKCSDGWWRGSY--NGQVGWFPSNYVTE 55
SH3_9 pfam14604
Variant SH3 domain;
726-771 7.82e-04

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 37.98  E-value: 7.82e-04
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gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRlaDGEKGWVPQAHV 771
Cdd:pfam14604   5 YEPKDDDELSLQRGDVITVIEESEDGWWEGIN--TGRTGLVPANYV 48
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
726-773 8.48e-04

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: 38.09  E-value: 8.48e-04
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gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEG-VRladGEKGWVPQAHVVE 773
Cdd:cd11823     8 YTANREDELSLQPGDIIEVHEKQDDGWWLGeLN---GKKGIFPATYVEE 53
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
726-774 9.35e-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: 38.13  E-value: 9.35e-04
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gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRlaDGEKGWVPQAHVVEI 774
Cdd:cd12061     8 FQQTNEDELSFSKGDVIHVTRVEEGGWWEGTH--NGRTGWFPSNYVREI 54
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
616-699 9.68e-04

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: 39.06  E-value: 9.68e-04
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gi 1039767156 616 SSKAVYLHLFNDCLLLSRRKELGKFAVFVHANMAE-LQVRDLSlklQGIPGHVFLLRLLHGQRarhqLLLRARTESEKQR 694
Cdd:cd00821    15 SWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGiLEVEEVS---PKERPHCFELVTPDGRT----YYLQADSEEERQE 87

                  ....*
gi 1039767156 695 WISAL 699
Cdd:cd00821    88 WLKAL 92
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
726-767 9.71e-04

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: 37.95  E-value: 9.71e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVP 767
Cdd:cd11845     8 YEARTDDDLSFKKGDRLQILDDSDGDWWLARHLSTGKEGYIP 49
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
726-776 1.15e-03

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: 37.67  E-value: 1.15e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVrlADGEKGWVPQAHVVEISS 776
Cdd:cd12060    10 FKQTNEDELSVCKGDIIYVTRVEEGGWWEGT--LNGKTGWFPSNYVREIKS 58
SH3_Intersectin1_4 cd11993
Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
717-775 1.18e-03

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: 38.18  E-value: 1.18e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039767156 717 RPQV-QCVRTYKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEK---GWVPQAHVVEIS 775
Cdd:cd11993     2 KPEIaQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYVKLLS 64
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
726-771 1.45e-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: 37.34  E-value: 1.45e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1039767156 726 YKALQPDELTLEKTDILAV-KTRTSDGWLEGvRLADGEKGWVPQAHV 771
Cdd:cd11761    10 YEAQRPDELTITEGEELEViEDGDGDGWVKA-RNKSGEVGYVPENYL 55
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
725-767 1.80e-03

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: 36.94  E-value: 1.80e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1039767156 725 TYKALQPDELTLEKTDILAVKTRTSD--GWLEGVrlADGEKGWVP 767
Cdd:cd11875     7 DYEAENEDELTLREGDIVTILSKDCEdkGWWKGE--LNGKRGVFP 49
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
726-771 2.00e-03

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: 36.97  E-value: 2.00e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRlaDGEKGWVPQAHV 771
Cdd:cd11824     8 YTAQEDDELSISKGDVVAVIEKGEDGWWTVER--NGQKGLVPGTYL 51
SH3_JIP1_like cd11801
Src homology 3 domain of JNK-interacting proteins 1 and 2, and similar domains; ...
731-773 2.09e-03

Src homology 3 domain of JNK-interacting proteins 1 and 2, and similar domains; JNK-interacting proteins (JIPs) function as scaffolding proteins for c-Jun N-terminal kinase (JNK) signaling pathways. They bind to components of Mitogen-activated protein kinase (MAPK) pathways such as JNK, MKK, and several MAP3Ks such as MLK and DLK. There are four JIPs (JIP1-4); all contain a JNK binding domain. JIP1 and JIP2 also contain SH3 and Phosphotyrosine-binding (PTB) domains. Both are highly expressed in the brain and pancreatic beta-cells. JIP1 functions as an adaptor linking motor to cargo during axonal transport and also is involved in regulating insulin secretion. JIP2 form complexes with fibroblast growth factor homologous factors (FHFs), which facilitates activation of the p38delta MAPK. The SH3 domain of JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212735  Cd Length: 55  Bit Score: 36.90  E-value: 2.09e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1039767156 731 PDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVE 773
Cdd:cd11801    13 EDEIELDIGDPVYVEQEADDLWCEGTNLRTGQRGIFPAAYVVE 55
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
726-767 2.70e-03

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: 36.52  E-value: 2.70e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRlADGEKGWVP 767
Cdd:cd11770     8 FQAEQEGDLSFKKGEVLRIISKRADGWWLAEN-SKGNRGLVP 48
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
726-774 3.44e-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: 36.36  E-value: 3.44e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039767156 726 YKALQPDELTLEKTDILA-VKTRTSDGWLEGVrlADGEKGWVPQAHVVEI 774
Cdd:cd12053     8 YDAVHEDELTIRVGEIIRnVKKLEEEGWLEGE--LNGRRGMFPDNFVKEI 55
SH3_RasGAP cd11788
Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein ...
717-774 3.67e-03

Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein activator, RASA1, or p120RasGAP, is part of the GAP1 family of GTPase-activating proteins. It is a 120kD cytosolic protein containing an SH3 domain flanked by two SH2 domains at the N-terminal end, a pleckstrin homology (PH) domain, a calcium dependent phospholipid binding domain (CaLB/C2), and a C-terminal catalytic GAP domain. It stimulates the GTPase activity of normal RAS p21. It acts as a positive effector of Ras in tumor cells. It also functions as a regulator downstream of tyrosine receptors such as those of PDGF, EGF, ephrin, and insulin, among others. The SH3 domain of RasGAP is unable to bind proline-rich sequences but have been shown to interact with protein partners such as the G3BP protein, Aurora kinases, and the Calpain small subunit 1. The RasGAP SH3 domain is necessary for the downstream signaling of Ras and it also influences Rho-mediated cytoskeletal reorganization. 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: 212722  Cd Length: 59  Bit Score: 36.20  E-value: 3.67e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039767156 717 RPQVQCVRTY-KALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVEI 774
Cdd:cd11788     1 RRRVRAILPYnKVPDTDELSFQKGDIFVVHNELEDGWLWVTSLRTGESGLVFRDLVEEL 59
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
726-772 3.86e-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: 3.86e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRlaDGEKGWVPQAHVV 772
Cdd:cd11809     8 YTGRSERELSFKKGDSLTLYRQVSDDWWRGQL--NGQDGLVPHKYIT 52
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
726-774 4.13e-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: 4.13e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1039767156 726 YKALQPDELTLEKTDILAVKTRTSDGWLEGVRLADGEKGWVPQAHVVEI 774
Cdd:cd11925     9 YKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRTGVSGVFPGNYVTPV 57
 
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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