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Conserved domains on  [gi|1907111731|ref|XP_036015216|]
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triple functional domain protein isoform X7 [Mus musculus]

Protein Classification

triple functional domain protein( domain architecture ID 12213596)

triple functional domain protein (Trio) is a large serine/threonine-protein kinase and Rho guanine nucleotide exchange factor that catalyzes the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates and functions as a GEF for Rac1, RhoG, and RhoA

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SH3-RhoG_link super family cl24983
SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved ...
 1715-1972 2.20e-150

SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved residues from higher eukaryotes is found to lie between an SH3 pfam00018 and the RhoGEF, pfam00621, domains. It is serine-rich and likely to be acidic and natively unstructured.


The actual alignment was detected with superfamily member pfam16609:

Pssm-ID: 465196  Cd Length: 261  Bit Score: 467.36  E-value: 2.20e-150
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1715 SLCIAHSRSSMEMEGIFNHKDSLSVSSNDASPPASVASLQP-HMIGAQSSPGPKRPGNTLRKWLTSPVRRLSSGKADGHA 1793
Cdd:pfam16609    1 MLCIAHSRSSMEMEGIFNHKDTLSVYSNDSIMPGSSATLQPgHGISSHASPGPKRPGNTLRKWLTSPVRRLSSGKADGHV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1794 KKLAHKHKKSREVRKS--ADAGSQKDSDDSAATPQDETIEERGRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADAVPLPP 1871
Cdd:pfam16609   81 KKLAHKHKKSREVRKSreITAGSQKDSDDSAATPQDETVEERVRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADSVPLPP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1872 PMAIQQHSLLQPDSQDDKASSRLLVRPTSSETPSAAELVSAIEELVKSKMALEDRPSSLLVDQGDSSSPSFNPSDNSLLS 1951
Cdd:pfam16609  161 PMAIQQHSLLQPDSQDDKTSSRLFVRPSSSETPSAAELVSAIEELVKSKMALEDRPSSLSVDQGDSSSPSFNPSDNSLLS 240

                          250       260
                   ....*....|....*....|.
gi 1907111731 1952 SSSPIDEMEERKCSSLKRRHY 1972
Cdd:pfam16609  241 SSSPISEMDERRSSFLKKRHY 261
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 2148-2286 1.20e-79

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 259.12  E-value: 1.20e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2148 VGRLQGFDGKIVAQGKLLLQDTFLVTDQDAGLLPRCKERRVFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKVSCLCLEE 2227
Cdd:cd13241      1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTQFSNPGYIYKNHIKVNKMSLEE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2228 NVESDPCKFALTSRTG-DAVETFVLHSSSPSVRQTWIHEINQILENQRNFLNALTSPIEY 2286
Cdd:cd13241     81 NVDGDPLRFALKSRDPnNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 1472-1594 7.97e-72

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


:

Pssm-ID: 270060  Cd Length: 123  Bit Score: 236.13  E-value: 7.97e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1472 MLEGFDENIESQGELILQESFQVWDPKTLIRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEHVEGD 1551
Cdd:cd13240      1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1907111731 1552 PCKFALWVGRTPTSDNKIVLKASSIENKQDWIKHIREVIQERT 1594
Cdd:cd13240     81 PCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQERI 123
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 2792-2875 2.08e-52

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd14113:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 263  Bit Score: 186.33  E-value: 2.08e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2792 WKDNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVL 2871
Cdd:cd14113      1 WKDNFDSFYSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYIL 80


                   ....
gi 1907111731 2872 VLEI 2875
Cdd:cd14113     81 VLEM 84
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1970-2143 7.28e-51

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: 178.65  E-value: 7.28e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1970 RHYVLQELVETERDYVRDLGCVVEGYMALMKEDGVPDDmKGKDKIVFGNIHQIYDWHRDFFLGELEKCLED---PEKLGS 2046
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLS-PEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdksGPRIGD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2047 LFVKHERRLHMYIVYCQNKPKSEHIVSEYI--DTFFEDLKQRLG---HRLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKA 2121
Cdd:cd00160     80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKkfNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159

                          170       180
                   ....*....|....*....|..
gi 1907111731 2122 SLDTSELEKAVEVMCIVPKRCN 2143
Cdd:cd00160    160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1295-1465 1.26e-44

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


:

Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 160.54  E-value: 1.26e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1295 FIMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPPGIVNkelIIFGNMQEIYEFHNnIFLKELEKY----EQLPEDVG 1370
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVE---LLFGNIEEIYEFHR-IFLKSLEERveewDKSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1371 HCFVTWADKFQMYVTYCKNKPDSTQLILEHAG--SYFDEIQQRHGLAN---SISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnKFFQEFLEKAESECgrlKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|...
gi 1907111731 1446 G---KGEIKDGLEVMLSVPKRAN 1465
Cdd:cd00160    159 GhedREDLKKALEAIKEVASQVN 181
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 2559-2617 1.31e-34

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212787  Cd Length: 59  Bit Score: 127.17  E-value: 1.31e-34
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2559 TMLVTHEYTAVKEDEINVYQGEVVQILASNQQNMFLVFRAATDQCPAAEGWIPGFVLGH 2617
Cdd:cd11853      1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVLGH 59
SH3_Kalirin_1 cd11852
First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 1659-1718 6.62e-32

First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212786  Cd Length: 62  Bit Score: 119.81  E-value: 6.62e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1659 ELTVVIHDFTACNSNELTIRRGQTVEVLERPHDKPDWCLVRTT--DRSPAAEGLVPCGSLCI 1718
Cdd:cd11852      1 ELTVVIEDFEATSSQELTVSKGQTVEVLERPSSRPDWCLVRTLeqDNSPPQEGLVPSSILCI 62
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 567-783 3.59e-25

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 105.99  E-value: 3.59e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  567 QLCVFQQDVQQVLDWIENHGEAFLSkhTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIY 646
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSS--TDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  647 QAAHQLEDRIQDFVRRVEQRKILLDMSV---SFHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKRFgqqqqttlQV 723
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALdlqQFFRDADDLEQWLEEKEAALASEDLGKDLESVEELLKKH--------KE 150

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  724 TVNVIKEGEDLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEELFQERKIKLE 783
Cdd:cd00176    151 LEEELEAHEPRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLE 210
I-set pfam07679
Immunoglobulin I-set domain;
2689-2780 4.31e-22

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 92.71  E-value: 4.31e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHnTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQ-PLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:pfam07679   79 AGEAEASAELTV 90
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
 69-204 5.53e-22

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


:

Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 95.06  E-value: 5.53e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731    69 LKEKVAYLSGGR--DKRGGPILTFPARS--NHDRIRQEDLRRLISYLACIPSEE---VCKRGFTVIVDMRGSK-----WD 136
Cdd:smart00516    2 LELLKAYIPGGRgyDKDGRPVLIERAGRfdLKSVTLEELLRYLVYVLEKILQEEkktGGIEGFTVIFDLKGLSmsnpdLS 81

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731   137 SIKPLLKILQESFPCCIHIALIIKPDNFWQ---KQRTNFGSSKFEFETNMVSL---EGLTKVVDPSQLTPEFDG 204
Cdd:smart00516   82 VLRKILKILQDHYPERLGKVYIINPPWFFRvlwKIIKPFLDEKTREKIRFVGNdskEELLEYIDKEQLPEELGG 155
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 908-1137 8.46e-19

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 87.50  E-value: 8.46e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  908 QLRHLQAEVKQVLGWIRNGESMLNAGLiTASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDMIRD 987
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSSTD-YGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  988 CAEKVASHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVlesleqeykreEDWCGGADKLGPNSETDHVTPMISKHLEQK 1067
Cdd:cd00176     80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDL-----------EQWLEEKEAALASEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1068 EAFLKACTlarrNADVFLKYLHRNSVSMPGmvTHIKAPEQQVKNILNELFQRENRVLHYWTMRKRRLDQC 1137
Cdd:cd00176    149 KELEEELE----AHEPRLKSLNELAEELLE--EGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 341-566 1.02e-17

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 84.42  E-value: 1.02e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  341 QLRLFEQDAEKMFDWITHnKGLFLNSyTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIK 420
Cdd:cd00176      1 KLQQFLRDADELEAWLSE-KEELLSS-TDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  421 QIANQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKyMSNVDSWCKACGEV----DLPSELQDLEDAIHHHQGIYEHITL 496
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRD-ADDLEQWLEEKEAAlaseDLGKDLESVEELLKKHKELEEELEA 157

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  497 AysevSQDGKSLLDKLQRPLTPGSSDSLTasanyskavhHVLDVIHEVLHHQRQLENIWQHRKVRLHQRL 566
Cdd:cd00176    158 H----EPRLKSLNELAEELLEEGHPDADE----------EIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 787-1014 1.71e-16

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 80.95  E-value: 1.71e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  787 QLRIFERDAidiiSDLESWNDELSQQMNDFDT-EDLTIAEQRLQHHADKALTMNNltfdviHQGQdllqyVNEVQASGvE 865
Cdd:cd00176      1 KLQQFLRDA----DELEAWLSEKEELLSSTDYgDDLESVEALLKKHEALEAELAA------HEER-----VEALNELG-E 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  866 LLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQVLGWIRNGESMLNAGLITaSSLQEAEQ 945
Cdd:cd00176     65 QLIEEGHPDAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAALASEDLG-KDLESVEE 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  946 LQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDM-IRDCAEKVASHWQQLMLKMEDRLKLVNASV 1014
Cdd:cd00176    144 LLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADEeIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 220-445 3.46e-15

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 77.10  E-value: 3.46e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  220 FEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKK--KVIKAPIEDLDLEGQKLLQriqssdsfpkknS 297
Cdd:cd00176      2 LQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAelAAHEERVEALNELGEQLIE------------E 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  298 GSGNADlqnllpKVSTMLDRLHSTRQHLHQMWHVRKLKLDQCFQLRLFEQDAEKMFDWIThNKGLFLNSyTEIGTSHPHA 377
Cdd:cd00176     70 GHPDAE------EIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLE-EKEAALAS-EDLGKDLESV 141

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731  378 MELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQ-QIKQIANQLEQEWKAFAAALDERSTLLD 445
Cdd:cd00176    142 EELLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADeEIEEKLEELNERWEELLELAEERQKKLE 210
SPEC smart00150
Spectrin repeats;
1143-1243 8.73e-14

Spectrin repeats;


:

Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 69.67  E-value: 8.73e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1143 FERSAKQALEWIHDNGEfyLSTHTSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIKKCVT 1222
Cdd:smart00150    3 FLRDADELEAWLEEKEQ--LLASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731  1223 AVDKRYRDFSLRMEKYRTSLE 1243
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
 
Name Accession Description Interval E-value
SH3-RhoG_link pfam16609
SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved ...
 1715-1972 2.20e-150

SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved residues from higher eukaryotes is found to lie between an SH3 pfam00018 and the RhoGEF, pfam00621, domains. It is serine-rich and likely to be acidic and natively unstructured.


Pssm-ID: 465196  Cd Length: 261  Bit Score: 467.36  E-value: 2.20e-150
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1715 SLCIAHSRSSMEMEGIFNHKDSLSVSSNDASPPASVASLQP-HMIGAQSSPGPKRPGNTLRKWLTSPVRRLSSGKADGHA 1793
Cdd:pfam16609    1 MLCIAHSRSSMEMEGIFNHKDTLSVYSNDSIMPGSSATLQPgHGISSHASPGPKRPGNTLRKWLTSPVRRLSSGKADGHV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1794 KKLAHKHKKSREVRKS--ADAGSQKDSDDSAATPQDETIEERGRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADAVPLPP 1871
Cdd:pfam16609   81 KKLAHKHKKSREVRKSreITAGSQKDSDDSAATPQDETVEERVRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADSVPLPP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1872 PMAIQQHSLLQPDSQDDKASSRLLVRPTSSETPSAAELVSAIEELVKSKMALEDRPSSLLVDQGDSSSPSFNPSDNSLLS 1951
Cdd:pfam16609  161 PMAIQQHSLLQPDSQDDKTSSRLFVRPSSSETPSAAELVSAIEELVKSKMALEDRPSSLSVDQGDSSSPSFNPSDNSLLS 240

                          250       260
                   ....*....|....*....|.
gi 1907111731 1952 SSSPIDEMEERKCSSLKRRHY 1972
Cdd:pfam16609  241 SSSPISEMDERRSSFLKKRHY 261
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 2148-2286 1.20e-79

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 259.12  E-value: 1.20e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2148 VGRLQGFDGKIVAQGKLLLQDTFLVTDQDAGLLPRCKERRVFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKVSCLCLEE 2227
Cdd:cd13241      1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTQFSNPGYIYKNHIKVNKMSLEE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2228 NVESDPCKFALTSRTG-DAVETFVLHSSSPSVRQTWIHEINQILENQRNFLNALTSPIEY 2286
Cdd:cd13241     81 NVDGDPLRFALKSRDPnNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 1472-1594 7.97e-72

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 236.13  E-value: 7.97e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1472 MLEGFDENIESQGELILQESFQVWDPKTLIRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEHVEGD 1551
Cdd:cd13240      1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1907111731 1552 PCKFALWVGRTPTSDNKIVLKASSIENKQDWIKHIREVIQERT 1594
Cdd:cd13240     81 PCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQERI 123
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 2792-2875 2.08e-52

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 186.33  E-value: 2.08e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2792 WKDNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVL 2871
Cdd:cd14113      1 WKDNFDSFYSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYIL 80


                   ....
gi 1907111731 2872 VLEI 2875
Cdd:cd14113     81 VLEM 84
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1970-2143 7.28e-51

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: 178.65  E-value: 7.28e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1970 RHYVLQELVETERDYVRDLGCVVEGYMALMKEDGVPDDmKGKDKIVFGNIHQIYDWHRDFFLGELEKCLED---PEKLGS 2046
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLS-PEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdksGPRIGD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2047 LFVKHERRLHMYIVYCQNKPKSEHIVSEYI--DTFFEDLKQRLG---HRLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKA 2121
Cdd:cd00160     80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKkfNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159

                          170       180
                   ....*....|....*....|..
gi 1907111731 2122 SLDTSELEKAVEVMCIVPKRCN 2143
Cdd:cd00160    160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1973-2143 1.28e-47

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: 169.02  E-value: 1.28e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1973 VLQELVETERDYVRDLGCVVEGYMALMKE--DGVPDDMKgkdkIVFGNIHQIYDWHRDFFLGELEKCLEDPEKLGSLFVK 2050
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKplSESEEEIK----TIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2051 HERRLHMYIVYCQNKPKSEHIVSEY------IDTFFEDLKQRLG-HRLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKASL 2123
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLlkknpkFRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156

                          170       180
                   ....*....|....*....|
gi 1907111731 2124 DTSELEKAVEVMCIVPKRCN 2143
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1973-2144 9.96e-47

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: 166.71  E-value: 9.96e-47
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1973 VLQELVETERDYVRDLGCVVEGYMALMKEDGVPDDMKGKDKIvFGNIHQIYDWHRDFfLGELEKCLED----PEKLGSLF 2048
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETL-FGNIEEIYEFHRDF-LDELEERIEEwddsVERIGDVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  2049 VKHERRLHMYIVYCQNKPKSEHIVSE--YIDTFFEDLKQRLGH----RLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKAS 2122
Cdd:smart00325   79 LKLEEFFKIYSEYCSNHPDALELLKKlkKNPRFQKFLKEIESSpqcrRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 1907111731  2123 LDTSELEKAVEVMCIVPKRCND 2144
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1295-1465 1.26e-44

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


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 160.54  E-value: 1.26e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1295 FIMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPPGIVNkelIIFGNMQEIYEFHNnIFLKELEKY----EQLPEDVG 1370
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVE---LLFGNIEEIYEFHR-IFLKSLEERveewDKSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1371 HCFVTWADKFQMYVTYCKNKPDSTQLILEHAG--SYFDEIQQRHGLAN---SISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnKFFQEFLEKAESECgrlKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|...
gi 1907111731 1446 G---KGEIKDGLEVMLSVPKRAN 1465
Cdd:cd00160    159 GhedREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1296-1466 2.94e-42

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: 154.00  E-value: 2.94e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1296 IMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPPgivNKELIIFGNMQEIYEFHNnIFLKELEKY----EQLPEDVGH 1371
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSP---NELETLFGNIEEIYEFHR-DFLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1372 CFVTWADKFQMYVTYCKNKPDSTQLI--LEHAGSYFDEIQQRHGLAN----SISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLkkLKKNPRFQKFLKEIESSPQcrrlTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 1907111731  1446 G---KGEIKDGLEVMLSVPKRAND 1466
Cdd:smart00325  157 DhedREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1296-1465 6.01e-41

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: 149.76  E-value: 6.01e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1296 IMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPpgivnKEL-IIFGNMQEIYEFHNNIFLKELEKYEQLPEDVGHCFV 1374
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESE-----EEIkTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1375 TWADKFQMYVTYCKNKPDSTQLI------LEHAGSYFDEIQQR---HGLanSISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:pfam00621   76 KFAPGFKVYSTYCSNYPKALKLLkkllkkNPKFRAFLEELEANpecRGL--DLNSFLIKPVQRIPRYPLLLKELLKHTPP 153

                          170       180
                   ....*....|....*....|...
gi 1907111731 1446 G---KGEIKDGLEVMLSVPKRAN 1465
Cdd:pfam00621  154 DhpdYEDLKKALEAIKEVAKQIN 176
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 2559-2617 1.31e-34

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212787  Cd Length: 59  Bit Score: 127.17  E-value: 1.31e-34
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2559 TMLVTHEYTAVKEDEINVYQGEVVQILASNQQNMFLVFRAATDQCPAAEGWIPGFVLGH 2617
Cdd:cd11853      1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVLGH 59
SH3_Kalirin_1 cd11852
First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 1659-1718 6.62e-32

First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212786  Cd Length: 62  Bit Score: 119.81  E-value: 6.62e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1659 ELTVVIHDFTACNSNELTIRRGQTVEVLERPHDKPDWCLVRTT--DRSPAAEGLVPCGSLCI 1718
Cdd:cd11852      1 ELTVVIEDFEATSSQELTVSKGQTVEVLERPSSRPDWCLVRTLeqDNSPPQEGLVPSSILCI 62
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 567-783 3.59e-25

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 105.99  E-value: 3.59e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  567 QLCVFQQDVQQVLDWIENHGEAFLSkhTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIY 646
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSS--TDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  647 QAAHQLEDRIQDFVRRVEQRKILLDMSV---SFHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKRFgqqqqttlQV 723
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALdlqQFFRDADDLEQWLEEKEAALASEDLGKDLESVEELLKKH--------KE 150

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  724 TVNVIKEGEDLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEELFQERKIKLE 783
Cdd:cd00176    151 LEEELEAHEPRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLE 210
I-set pfam07679
Immunoglobulin I-set domain;
2689-2780 4.31e-22

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 92.71  E-value: 4.31e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHnTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQ-PLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:pfam07679   79 AGEAEASAELTV 90
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
 69-204 5.53e-22

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 95.06  E-value: 5.53e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731    69 LKEKVAYLSGGR--DKRGGPILTFPARS--NHDRIRQEDLRRLISYLACIPSEE---VCKRGFTVIVDMRGSK-----WD 136
Cdd:smart00516    2 LELLKAYIPGGRgyDKDGRPVLIERAGRfdLKSVTLEELLRYLVYVLEKILQEEkktGGIEGFTVIFDLKGLSmsnpdLS 81

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731   137 SIKPLLKILQESFPCCIHIALIIKPDNFWQ---KQRTNFGSSKFEFETNMVSL---EGLTKVVDPSQLTPEFDG 204
Cdd:smart00516   82 VLRKILKILQDHYPERLGKVYIINPPWFFRvlwKIIKPFLDEKTREKIRFVGNdskEELLEYIDKEQLPEELGG 155
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 908-1137 8.46e-19

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 87.50  E-value: 8.46e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  908 QLRHLQAEVKQVLGWIRNGESMLNAGLiTASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDMIRD 987
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSSTD-YGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  988 CAEKVASHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVlesleqeykreEDWCGGADKLGPNSETDHVTPMISKHLEQK 1067
Cdd:cd00176     80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDL-----------EQWLEEKEAALASEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1068 EAFLKACTlarrNADVFLKYLHRNSVSMPGmvTHIKAPEQQVKNILNELFQRENRVLHYWTMRKRRLDQC 1137
Cdd:cd00176    149 KELEEELE----AHEPRLKSLNELAEELLE--EGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 341-566 1.02e-17

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 84.42  E-value: 1.02e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  341 QLRLFEQDAEKMFDWITHnKGLFLNSyTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIK 420
Cdd:cd00176      1 KLQQFLRDADELEAWLSE-KEELLSS-TDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  421 QIANQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKyMSNVDSWCKACGEV----DLPSELQDLEDAIHHHQGIYEHITL 496
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRD-ADDLEQWLEEKEAAlaseDLGKDLESVEELLKKHKELEEELEA 157

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  497 AysevSQDGKSLLDKLQRPLTPGSSDSLTasanyskavhHVLDVIHEVLHHQRQLENIWQHRKVRLHQRL 566
Cdd:cd00176    158 H----EPRLKSLNELAEELLEEGHPDADE----------EIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 787-1014 1.71e-16

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 80.95  E-value: 1.71e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  787 QLRIFERDAidiiSDLESWNDELSQQMNDFDT-EDLTIAEQRLQHHADKALTMNNltfdviHQGQdllqyVNEVQASGvE 865
Cdd:cd00176      1 KLQQFLRDA----DELEAWLSEKEELLSSTDYgDDLESVEALLKKHEALEAELAA------HEER-----VEALNELG-E 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  866 LLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQVLGWIRNGESMLNAGLITaSSLQEAEQ 945
Cdd:cd00176     65 QLIEEGHPDAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAALASEDLG-KDLESVEE 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  946 LQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDM-IRDCAEKVASHWQQLMLKMEDRLKLVNASV 1014
Cdd:cd00176    144 LLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADEeIEEKLEELNERWEELLELAEERQKKLEEAL 213
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2696-2780 4.98e-16

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 75.23  E-value: 4.98e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  2696 SEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVNDMGSASSS 2775
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSG-STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1907111731  2776 ASLRV 2780
Cdd:smart00410   81 TTLTV 85
SEC14 cd00170
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
 74-204 2.98e-15

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 469559 [Multi-domain]  Cd Length: 156  Bit Score: 75.45  E-value: 2.98e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   74 AYLSGGRDKRGGPILTFPAR-SNHDRIRQEDLRRLISYL--ACIPSEEVCKRGFTVIVDMRGSKW------DSIKPLLKI 144
Cdd:cd00170     11 IGYLGGRDKEGRPVLVFRAGwDPPKLLDLEELLRYLVYLleKALRELEEQVEGFVVIIDLKGFSLsnlsdlSLLKKLLKI 90

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  145 LQESFPCCIHIALIIKPDNF----WQ------KQRTnfgSSKFEFETNmvSLEGLTKVVDPSQLTPEFDG 204
Cdd:cd00170     91 LQDHYPERLKKIYIVNAPWIfsalWKivkpflSEKT---RKKIVFLGS--DLEELLEYIDPDQLPKELGG 155
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 220-445 3.46e-15

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 77.10  E-value: 3.46e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  220 FEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKK--KVIKAPIEDLDLEGQKLLQriqssdsfpkknS 297
Cdd:cd00176      2 LQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAelAAHEERVEALNELGEQLIE------------E 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  298 GSGNADlqnllpKVSTMLDRLHSTRQHLHQMWHVRKLKLDQCFQLRLFEQDAEKMFDWIThNKGLFLNSyTEIGTSHPHA 377
Cdd:cd00176     70 GHPDAE------EIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLE-EKEAALAS-EDLGKDLESV 141

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731  378 MELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQ-QIKQIANQLEQEWKAFAAALDERSTLLD 445
Cdd:cd00176    142 EELLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADeEIEEKLEELNERWEELLELAEERQKKLE 210
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 2800-2874 5.06e-15

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 77.57  E-value: 5.06e-15
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731  2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK--RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKkdRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVME 77
Pkinase pfam00069
Protein kinase domain;
2800-2874 3.74e-14

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 74.20  E-value: 3.74e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNK---KLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKekiKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLE 78
SPEC smart00150
Spectrin repeats;
1143-1243 8.73e-14

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 69.67  E-value: 8.73e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1143 FERSAKQALEWIHDNGEfyLSTHTSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIKKCVT 1222
Cdd:smart00150    3 FLRDADELEAWLEEKEQ--LLASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731  1223 AVDKRYRDFSLRMEKYRTSLE 1243
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
SPEC smart00150
Spectrin repeats;
571-671 1.33e-13

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 68.90  E-value: 1.33e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   571 FQQDVQQVLDWIENHgEAFLSkHTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIYQAAH 650
Cdd:smart00150    3 FLRDADELEAWLEEK-EQLLA-SEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731   651 QLEDRIQDFVRRVEQRKILLD 671
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 2694-2780 2.05e-13

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 67.80  E-value: 2.05e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITWkgpehntLNNDDHYSISY--SDIGEATLKIIGVSTEDDGIYTCIAVNDMGS 2771
Cdd:cd20978      7 PEKNVVVKGGQDVTLPCQVTGVPQPKITW-------LHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79


                   ....*....
gi 1907111731 2772 ASSSASLRV 2780
Cdd:cd20978     80 IYTETLLHV 88
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 1139-1246 5.07e-13

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 70.55  E-value: 5.07e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1139 QYVVFERSAKQALEWIHDNGEFYLSThtSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIK 1218
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSST--DYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100
                   ....*....|....*....|....*...
gi 1907111731 1219 KCVTAVDKRYRDFSLRMEKYRTSLEKAL 1246
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEAL 106
SPEC smart00150
Spectrin repeats;
910-1008 1.50e-11

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 63.12  E-value: 1.50e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   910 RHLQAEVKQVLGWIRNGESMLNAgLITASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDMIRDCA 989
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLLAS-EDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERL 79

                            90
                    ....*....|....*....
gi 1907111731   990 EKVASHWQQLMLKMEDRLK 1008
Cdd:smart00150   80 EELNERWEELKELAEERRQ 98
SPEC smart00150
Spectrin repeats;
345-445 1.77e-11

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 62.73  E-value: 1.77e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   345 FEQDAEKMFDWITHNKGLFlnSYTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIKQIAN 424
Cdd:smart00150    3 FLRDADELEAWLEEKEQLL--ASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731   425 QLEQEWKAFAAALDERSTLLD 445
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
CRAL_TRIO_2 pfam13716
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
 84-211 4.30e-10

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.


Pssm-ID: 463965 [Multi-domain]  Cd Length: 140  Bit Score: 60.03  E-value: 4.30e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   84 GGPILTFPARS-NHDRIRQEDLRRLISYLACIPSEEVCKRGFTVIVDMRGSKWDS------IKPLLKILQESFPCCIHIA 156
Cdd:pfam13716    1 GRPVLVFISKLlPSRPASLDDLDRLLFYLLKTLSEKLKGKPFVVVVDHTGVTSENfpslsfLKKAYDLLPRAFKKNLKAV 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  157 LIIKPDNFWQKQ----RTNFGSSKFEFETNMVS-LEGLTKVVDPSQLTPEFDGCLEYNHE 211
Cdd:pfam13716   81 YVVHPSTFLRTFlktlGSLLGSKKLRKKVHYVSsLSELWEGIDREQLPTELPGVLSYDEE 140
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 908-999 7.21e-08

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 52.71  E-value: 7.21e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  908 QLRHLQAEVKQVLGWIRNGESMLNAGLItASSLQEAEQLQREHEQFQHAIEkTHQSALQ-VQQKAEAMLQANHYDMDMIR 986
Cdd:pfam00435    2 LLQQFFRDADDLESWIEEKEALLSSEDY-GKDLESVQALLKKHKALEAELA-AHQDRVEaLNELAEKLIDEGHYASEEIQ 79

                           90
                   ....*....|...
gi 1907111731  987 DCAEKVASHWQQL 999
Cdd:pfam00435   80 ERLEELNERWEQL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1505-1590 1.26e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 52.18  E-value: 1.26e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1505 RERHLFLFEMSLVFSKevkDSSGRSKYLYKSKLFTSELGVTEHVEGD----PCKFALWVGrTPTSDNKIVLKASSIENKQ 1580
Cdd:pfam00169   19 KKRYFVLFDGSLLYYK---DDKSGKSKEPKGSISLSGCEVVEVVASDspkrKFCFELRTG-ERTGKRTYLLQAESEEERK 94

                           90
                   ....*....|
gi 1907111731 1581 DWIKHIREVI 1590
Cdd:pfam00169   95 DWIKAIQSAI 104
SPEC smart00150
Spectrin repeats;
221-337 1.39e-07

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 51.95  E-value: 1.39e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   221 EEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKKKV--IKAPIEDLDLEGQKLLQriqssdsfpkknSG 298
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLLASEDLGKDLESVEALLKKHEAFEAELeaHEERVEALNELGEQLIE------------EG 68

                            90       100       110
                    ....*....|....*....|....*....|....*....
gi 1907111731   299 SGNAdlqnllPKVSTMLDRLHSTRQHLHQMWHVRKLKLD 337
Cdd:smart00150   69 HPDA------EEIEERLEELNERWEELKELAEERRQKLE 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1483-1591 1.90e-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: 51.40  E-value: 1.90e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1483 QGELILQEsfqvwdpKTLIRKGRERHLFLFEMSLVFSKevkDSSGRSKYLYKSKLFTSELGVTEHVEGD----PCKFALW 1558
Cdd:smart00233    4 EGWLYKKS-------GGGKKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDPDsskkPHCFEIK 73

                            90       100       110
                    ....*....|....*....|....*....|...
gi 1907111731  1559 VGRTPTsdnkIVLKASSIENKQDWIKHIREVIQ 1591
Cdd:smart00233   74 TSDRKT----LLLQAESEEEREKWVEALRKAIA 102
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1969-2135 2.27e-07

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 56.82  E-value: 2.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1969 RRHYVLQELVETERDYVRDLGCVVEGYMALMKE-DGVPDDMKGK-DKIVFGNIHQIYDWHRDFfLGELEK--CLED-PEK 2043
Cdd:COG5422    484 KRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEEsNIIPENARRNfIKHVFANINEIYAVNSKL-LKALTNrqCLSPiVNG 562

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2044 LGSLFVKHERRLHMYIVYCQNKP------KSEHIVSEYIDTFFED-LKQRLGHRLQLTDLLIKPVQRIMKYQLLLKDFLK 2116
Cdd:COG5422    563 IADIFLDYVPKFEPFIKYGASQPyakyefEREKSVNPNFARFDHEvERLDESRKLELDGYLTKPTTRLARYPLLLEEVLK 642

                          170
                   ....*....|....*....
gi 1907111731 2117 YSKKASLDTSELEKAVEVM 2135
Cdd:COG5422    643 FTDPDNPDTEDIPKVIDML 661
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 1662-1713 2.44e-07

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: 49.46  E-value: 2.44e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1907111731  1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVRTTDRspaAEGLVPC 1713
Cdd:smart00326    6 RALYDYTAQDPDELSFKKGDIITVLEKSDD--GWWKGRLGRG---KEGLFPS 52
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 1143-1243 6.31e-07

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 50.01  E-value: 6.31e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1143 FERSAKQALEWIHDNGEFYLSThtSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIKKCVT 1222
Cdd:pfam00435    6 FFRDADDLESWIEEKEALLSSE--DYGKDLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQERLE 83

                           90       100
                   ....*....|....*....|.
gi 1907111731 1223 AVDKRYRDFSLRMEKYRTSLE 1243
Cdd:pfam00435   84 ELNERWEQLLELAAERKQKLE 104
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1280-1457 1.05e-06

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 54.90  E-value: 1.05e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1280 HELNEEKRKSARRKEFIMAELIQTEKAYVRDLRECMDTY---LWEMTsgveeIPPGIVNKELI--IFGNMQEIYEFhNNI 1354
Cdd:COG5422    472 KEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWikpLEESN-----IIPENARRNFIkhVFANINEIYAV-NSK 545

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1355 FLKELEK---YEQLPEDVGHCFVTWADKFQMYVTYCKNKPDSTQLIlEHAGS-------YFDEIQ-----QRHGlansIS 1419
Cdd:COG5422    546 LLKALTNrqcLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEF-EREKSvnpnfarFDHEVErldesRKLE----LD 620

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1907111731 1420 SYLIKPVQRITKYQLLLKELLTCCEEGKGEIKDGLEVM 1457
Cdd:COG5422    621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVI 658
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 341-444 3.08e-06

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 48.08  E-value: 3.08e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  341 QLRLFEQDAEKMFDWIThNKGLFLNSyTEIGTSHPHAMELQTQHNHFAMNcMNVY-VNINRIMSVANRLVESGHYASQQI 419
Cdd:pfam00435    2 LLQQFFRDADDLESWIE-EKEALLSS-EDYGKDLESVQALLKKHKALEAE-LAAHqDRVEALNELAEKLIDEGHYASEEI 78

                           90       100
                   ....*....|....*....|....*
gi 1907111731  420 KQIANQLEQEWKAFAAALDERSTLL 444
Cdd:pfam00435   79 QERLEELNERWEQLLELAAERKQKL 103
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 1662-1713 4.87e-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: 4.87e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVRTTDRSpaaEGLVPC 1713
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSED--GWWKGRNKGGK---EGLIPS 47
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 2175-2270 9.91e-06

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: 46.77  E-value: 9.91e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  2175 QDAGLLPRCKERRVFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKVSClCLEENVESDPCKFALTSRTGdavETFVLHSS 2254
Cdd:smart00233   10 KSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVRE-APDPDSSKKPHCFEIKTSDR---KTLLLQAE 85

                            90
                    ....*....|....*.
gi 1907111731  2255 SPSVRQTWIHEINQIL 2270
Cdd:smart00233   86 SEEEREKWVEALRKAI 101
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 571-670 1.02e-05

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 46.54  E-value: 1.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  571 FQQDVQQVLDWIENHgEAFLSKhTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIYQAAH 650
Cdd:pfam00435    6 FFRDADDLESWIEEK-EALLSS-EDYGKDLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQERLE 83

                           90       100
                   ....*....|....*....|
gi 1907111731  651 QLEDRIQDFVRRVEQRKILL 670
Cdd:pfam00435   84 ELNERWEQLLELAAERKQKL 103
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
2803-2874 1.11e-05

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 50.78  E-value: 1.11e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 2803 VAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK----RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:COG0515     12 LRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAAdpeaRERFRREARALARLNHPNIVRVYDVGEEDGRPYLVME 87
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 2175-2271 1.54e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.02  E-value: 1.54e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2175 QDAGLLPRCKERRVFLFEQIVIFSepldkKKGFSMPGFLFKNSIKVSCLCLEENVESD----PCKFALTSRTGDAVETFV 2250
Cdd:pfam00169   10 KGGGKKKSWKKRYFVLFDGSLLYY-----KDDKSGKSKEPKGSISLSGCEVVEVVASDspkrKFCFELRTGERTGKRTYL 84

                           90       100
                   ....*....|....*....|.
gi 1907111731 2251 LHSSSPSVRQTWIHEINQILE 2271
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSAIR 105
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 733-1039 1.90e-05

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


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 50.44  E-value: 1.90e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  733 DLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEEL---FQERKIKLElFLQLRIFERDaiDIISDLESWNDEL 809
Cdd:TIGR02168  217 ELKAELRELELALLVLRLEELREELEELQEELKEAEEELEELtaeLQELEEKLE-ELRLEVSELE--EEIEELQKELYAL 293

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  810 SQQMNDFdtedltiaEQRLQHHADKALTMNNLTFDVIHQGQDLLQYVNEVQASGVELLCDRDVDMA--TRVQDLLEFLHE 887
Cdd:TIGR02168  294 ANEISRL--------EQQKQILRERLANLERQLEELEAQLEELESKLDELAEELAELEEKLEELKEelESLEAELEELEA 365

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  888 KQQELDLAAEQHRKHLEQcvqlrhLQAEVKQvlgwIRNGESMLNAGLITASSlqEAEQLQREHEQFQHAIEkTHQSALQV 967
Cdd:TIGR02168  366 ELEELESRLEELEEQLET------LRSKVAQ----LELQIASLNNEIERLEA--RLERLEDRRERLQQEIE-ELLKKLEE 432

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731  968 QQKAEAMLQANHYDMdMIRDCAEKVASHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVLESLEQEYKREED 1039
Cdd:TIGR02168  433 AELKELQAELEELEE-ELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQARLDSLERLQENLEG 503
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 2806-2874 4.54e-05

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 48.28  E-value: 4.54e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:PTZ00263    26 LGTGSFGRVRIAKHKGTGEYYAIKCLKKReILKMKQVQHvaqEKSILMELSHPFIVNMMCSFQDENRVYFLLE 98
MukB COG3096
Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell ...
 574-914 1.22e-04

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 442330 [Multi-domain]  Cd Length: 1470  Bit Score: 48.02  E-value: 1.22e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  574 DVQQVLDwienhgeaflSKHTgvgkslhraRALQkrhedfeevaqntYTNADKLLEAAEQLAQTGECDPEEI--YQAAHQ 651
Cdd:COG3096    400 DYQQALD----------VQQT---------RAIQ-------------YQQAVQALEKARALCGLPDLTPENAedYLAAFR 447

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  652 L-EDRIQDFVRRVEQRKILLDMSVSFHTHVKELwtwleeLQKeLLDDVYAESV-EAVQDLIKRFgqqqqttlQVTVNVIK 729
Cdd:COG3096    448 AkEQQATEEVLELEQKLSVADAARRQFEKAYEL------VCK-IAGEVERSQAwQTARELLRRY--------RSQQALAQ 512

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  730 EGEDLIQQLRDsaissnktphnssinhIETVLQQLDEAQSQMEELFQERKIKLELFLQLRiferdaiDIISDLESWNDEL 809
Cdd:COG3096    513 RLQQLRAQLAE----------------LEQRLRQQQNAERLLEEFCQRIGQQLDAAEELE-------ELLAELEAQLEEL 569

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  810 SQQMNDFdTEDLTIAEQRLQHHADKaltMNNLTFD--VIHQGQDLLQYVNEvqASGVELLCDRDVdMATRvQDLLEFLHE 887
Cdd:COG3096    570 EEQAAEA-VEQRSELRQQLEQLRAR---IKELAARapAWLAAQDALERLRE--QSGEALADSQEV-TAAM-QQLLERERE 641

                          330       340
                   ....*....|....*....|....*..
gi 1907111731  888 KQQELDLAAEQhRKHLEQcvQLRHLQA 914
Cdd:COG3096    642 ATVERDELAAR-KQALES--QIERLSQ 665
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 766-977 1.76e-04

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


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 47.24  E-value: 1.76e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  766 EAQSQMEELfQERKIKLeLFLQLRIFERDAIDIISDLESWNDELSQQMNDFDTEDLTIAEQRLQHHAdkaltmnnLTFDV 845
Cdd:COG1196    214 RYRELKEEL-KELEAEL-LLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEE--------LELEL 283

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  846 IHQGQDLLQYVNEVQA--SGVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQVLgwI 923
Cdd:COG1196    284 EEAQAEEYELLAELARleQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAEL--A 361

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907111731  924 RNGESMLNAGLITASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQA 977
Cdd:COG1196    362 EAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLER 415
sbcc TIGR00618
exonuclease SbcC; All proteins in this family for which functions are known are part of an ...
 417-973 1.99e-04

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129705 [Multi-domain]  Cd Length: 1042  Bit Score: 47.27  E-value: 1.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  417 QQIKQIANQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKYMSNVDSWCKACGEVDLPSELQDLEDAIHHHQGIYEHITl 496
Cdd:TIGR00618  314 TELQSKMRSRAKLLMKRAAHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLT- 392

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  497 aysEVSQDGKSLLDKLQRplTPGSSDSLTASAN---YSKAVHHVLDVIHEVLHHQRQL--ENIWQHRK------VRLHQR 565
Cdd:TIGR00618  393 ---QKLQSLCKELDILQR--EQATIDTRTSAFRdlqGQLAHAKKQQELQQRYAELCAAaiTCTAQCEKlekihlQESAQS 467

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  566 LQLCVFQ-QDVQQVLDWIENHG---EAFLSKHTGV-----GKSLHRARALQKRHE---DFEEVAQNTYTNAdKLLEAAEQ 633
Cdd:TIGR00618  468 LKEREQQlQTKEQIHLQETRKKavvLARLLELQEEpcplcGSCIHPNPARQDIDNpgpLTRRMQRGEQTYA-QLETSEED 546

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  634 LAQTGECDPEEIYQAAHQLEDRIQDFVRRVEQRKILLDMSVSFHTHVKELWTWLE---ELQKELLDDVYAESVE-----A 705
Cdd:TIGR00618  547 VYHQLTSERKQRASLKEQMQEIQQSFSILTQCDNRSKEDIPNLQNITVRLQDLTEklsEAEDMLACEQHALLRKlqpeqD 626

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  706 VQDLIKRFGQQQQTTLQVTVNVIKEGEDLIQQ-LRDSAISSNKTPHNSsinhIETVLQQLDEAQSQMEELFQERKIKLEL 784
Cdd:TIGR00618  627 LQDVRLHLQQCSQELALKLTALHALQLTLTQErVREHALSIRVLPKEL----LASRQLALQKMQSEKEQLTYWKEMLAQC 702

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  785 FLQLRIFERDAIDIISDLESWNDELSQQMNDFDTEDLTIAE--QRLQHHADKALtmnnltfdvihQGQDLLQYVNEVQAS 862
Cdd:TIGR00618  703 QTLLRELETHIEEYDREFNEIENASSSLGSDLAAREDALNQslKELMHQARTVL-----------KARTEAHFNNNEEVT 771

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  863 GVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQvlgwiRNGESMLNAGLITASSLQE 942
Cdd:TIGR00618  772 AALQTGAELSHLAAEIQFFNRLREEDTHLLKTLEAEIGQEIPSDEDILNLQCETLV-----QEEEQFLSRLEEKSATLGE 846

                          570       580       590
                   ....*....|....*....|....*....|..
gi 1907111731  943 AEQLQREHEQ-FQHAIEKTHQSALQVQQKAEA 973
Cdd:TIGR00618  847 ITHQLLKYEEcSKQLAQLTQEQAKIIQLSDKL 878
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 220-338 5.83e-04

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 41.54  E-value: 5.83e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  220 FEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKK--KVIKAPIEDLDLEGQKLLQRiQSSDSfpkkns 297
Cdd:pfam00435    3 LQQFFRDADDLESWIEEKEALLSSEDYGKDLESVQALLKKHKALEAelAAHQDRVEALNELAEKLIDE-GHYAS------ 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907111731  298 gsgnadlqnllPKVSTMLDRLHSTRQHLHQMWHVRKLKLDQ 338
Cdd:pfam00435   76 -----------EEIQERLEELNERWEQLLELAAERKQKLEE 105
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 544-846 1.03e-03

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


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 45.05  E-value: 1.03e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  544 VLHHQRQLENIWQHRKVRLHQRLQLCVFQQDVQQVLDWIENHGEAFLSKHTGVGKSLHRARALQKRHEDFEEVAQNTYTN 623
Cdd:TIGR02168  672 ILERRREIEELEEKIEELEEKIAELEKALAELRKELEELEEELEQLRKELEELSRQISALRKDLARLEAEVEQLEERIAQ 751

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  624 ADKLLEAAEQLAQTGECDPEEIYQAAHQLEDRIQDFVRRVEQRKILLdmsvsfhthvKELWTWLEELQKEL--LDDVYAE 701
Cdd:TIGR02168  752 LSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEEL----------KALREALDELRAELtlLNEEAAN 821

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  702 SVEAVQDLIKRfgqqqqttlqvTVNVIKEGEDLIQQLRDSAissnktphnssiNHIETVLQQLDEAQSQMEELFQERKIK 781
Cdd:TIGR02168  822 LRERLESLERR-----------IAATERRLEDLEEQIEELS------------EDIESLAAEIEELEELIEELESELEAL 878

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731  782 LELF----LQLRIFERDAIDIISDLESWN----------DELSQQMNDFDTEdLTIAEQRLQHHADKALTMNNLTFDVI 846
Cdd:TIGR02168  879 LNERasleEALALLRSELEELSEELRELEskrselrrelEELREKLAQLELR-LEGLEVRIDNLQERLSEEYSLTLEEA 956
 
Name Accession Description Interval E-value
SH3-RhoG_link pfam16609
SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved ...
 1715-1972 2.20e-150

SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved residues from higher eukaryotes is found to lie between an SH3 pfam00018 and the RhoGEF, pfam00621, domains. It is serine-rich and likely to be acidic and natively unstructured.


Pssm-ID: 465196  Cd Length: 261  Bit Score: 467.36  E-value: 2.20e-150
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1715 SLCIAHSRSSMEMEGIFNHKDSLSVSSNDASPPASVASLQP-HMIGAQSSPGPKRPGNTLRKWLTSPVRRLSSGKADGHA 1793
Cdd:pfam16609    1 MLCIAHSRSSMEMEGIFNHKDTLSVYSNDSIMPGSSATLQPgHGISSHASPGPKRPGNTLRKWLTSPVRRLSSGKADGHV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1794 KKLAHKHKKSREVRKS--ADAGSQKDSDDSAATPQDETIEERGRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADAVPLPP 1871
Cdd:pfam16609   81 KKLAHKHKKSREVRKSreITAGSQKDSDDSAATPQDETVEERVRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADSVPLPP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1872 PMAIQQHSLLQPDSQDDKASSRLLVRPTSSETPSAAELVSAIEELVKSKMALEDRPSSLLVDQGDSSSPSFNPSDNSLLS 1951
Cdd:pfam16609  161 PMAIQQHSLLQPDSQDDKTSSRLFVRPSSSETPSAAELVSAIEELVKSKMALEDRPSSLSVDQGDSSSPSFNPSDNSLLS 240

                          250       260
                   ....*....|....*....|.
gi 1907111731 1952 SSSPIDEMEERKCSSLKRRHY 1972
Cdd:pfam16609  241 SSSPISEMDERRSSFLKKRHY 261
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 2148-2286 1.20e-79

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 259.12  E-value: 1.20e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2148 VGRLQGFDGKIVAQGKLLLQDTFLVTDQDAGLLPRCKERRVFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKVSCLCLEE 2227
Cdd:cd13241      1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTQFSNPGYIYKNHIKVNKMSLEE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2228 NVESDPCKFALTSRTG-DAVETFVLHSSSPSVRQTWIHEINQILENQRNFLNALTSPIEY 2286
Cdd:cd13241     81 NVDGDPLRFALKSRDPnNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 1472-1594 7.97e-72

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 236.13  E-value: 7.97e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1472 MLEGFDENIESQGELILQESFQVWDPKTLIRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEHVEGD 1551
Cdd:cd13240      1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1907111731 1552 PCKFALWVGRTPTSDNKIVLKASSIENKQDWIKHIREVIQERT 1594
Cdd:cd13240     81 PCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQERI 123
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 2792-2875 2.08e-52

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 186.33  E-value: 2.08e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2792 WKDNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVL 2871
Cdd:cd14113      1 WKDNFDSFYSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYIL 80


                   ....
gi 1907111731 2872 VLEI 2875
Cdd:cd14113     81 VLEM 84
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1970-2143 7.28e-51

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: 178.65  E-value: 7.28e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1970 RHYVLQELVETERDYVRDLGCVVEGYMALMKEDGVPDDmKGKDKIVFGNIHQIYDWHRDFFLGELEKCLED---PEKLGS 2046
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLS-PEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdksGPRIGD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2047 LFVKHERRLHMYIVYCQNKPKSEHIVSEYI--DTFFEDLKQRLG---HRLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKA 2121
Cdd:cd00160     80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKkfNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159

                          170       180
                   ....*....|....*....|..
gi 1907111731 2122 SLDTSELEKAVEVMCIVPKRCN 2143
Cdd:cd00160    160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1973-2143 1.28e-47

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: 169.02  E-value: 1.28e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1973 VLQELVETERDYVRDLGCVVEGYMALMKE--DGVPDDMKgkdkIVFGNIHQIYDWHRDFFLGELEKCLEDPEKLGSLFVK 2050
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKplSESEEEIK----TIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2051 HERRLHMYIVYCQNKPKSEHIVSEY------IDTFFEDLKQRLG-HRLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKASL 2123
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLlkknpkFRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156

                          170       180
                   ....*....|....*....|
gi 1907111731 2124 DTSELEKAVEVMCIVPKRCN 2143
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1973-2144 9.96e-47

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: 166.71  E-value: 9.96e-47
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1973 VLQELVETERDYVRDLGCVVEGYMALMKEDGVPDDMKGKDKIvFGNIHQIYDWHRDFfLGELEKCLED----PEKLGSLF 2048
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETL-FGNIEEIYEFHRDF-LDELEERIEEwddsVERIGDVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  2049 VKHERRLHMYIVYCQNKPKSEHIVSE--YIDTFFEDLKQRLGH----RLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKAS 2122
Cdd:smart00325   79 LKLEEFFKIYSEYCSNHPDALELLKKlkKNPRFQKFLKEIESSpqcrRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 1907111731  2123 LDTSELEKAVEVMCIVPKRCND 2144
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1295-1465 1.26e-44

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


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 160.54  E-value: 1.26e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1295 FIMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPPGIVNkelIIFGNMQEIYEFHNnIFLKELEKY----EQLPEDVG 1370
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVE---LLFGNIEEIYEFHR-IFLKSLEERveewDKSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1371 HCFVTWADKFQMYVTYCKNKPDSTQLILEHAG--SYFDEIQQRHGLAN---SISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnKFFQEFLEKAESECgrlKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|...
gi 1907111731 1446 G---KGEIKDGLEVMLSVPKRAN 1465
Cdd:cd00160    159 GhedREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1296-1466 2.94e-42

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: 154.00  E-value: 2.94e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1296 IMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPPgivNKELIIFGNMQEIYEFHNnIFLKELEKY----EQLPEDVGH 1371
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSP---NELETLFGNIEEIYEFHR-DFLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1372 CFVTWADKFQMYVTYCKNKPDSTQLI--LEHAGSYFDEIQQRHGLAN----SISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLkkLKKNPRFQKFLKEIESSPQcrrlTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 1907111731  1446 G---KGEIKDGLEVMLSVPKRAND 1466
Cdd:smart00325  157 DhedREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1296-1465 6.01e-41

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: 149.76  E-value: 6.01e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1296 IMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPpgivnKEL-IIFGNMQEIYEFHNNIFLKELEKYEQLPEDVGHCFV 1374
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESE-----EEIkTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1375 TWADKFQMYVTYCKNKPDSTQLI------LEHAGSYFDEIQQR---HGLanSISSYLIKPVQRITKYQLLLKELLTCCEE 1445
Cdd:pfam00621   76 KFAPGFKVYSTYCSNYPKALKLLkkllkkNPKFRAFLEELEANpecRGL--DLNSFLIKPVQRIPRYPLLLKELLKHTPP 153

                          170       180
                   ....*....|....*....|...
gi 1907111731 1446 G---KGEIKDGLEVMLSVPKRAN 1465
Cdd:pfam00621  154 DhpdYEDLKKALEAIKEVAKQIN 176
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 2559-2617 1.31e-34

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212787  Cd Length: 59  Bit Score: 127.17  E-value: 1.31e-34
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2559 TMLVTHEYTAVKEDEINVYQGEVVQILASNQQNMFLVFRAATDQCPAAEGWIPGFVLGH 2617
Cdd:cd11853      1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVLGH 59
SH3_Kalirin_1 cd11852
First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 1659-1718 6.62e-32

First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212786  Cd Length: 62  Bit Score: 119.81  E-value: 6.62e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1659 ELTVVIHDFTACNSNELTIRRGQTVEVLERPHDKPDWCLVRTT--DRSPAAEGLVPCGSLCI 1718
Cdd:cd11852      1 ELTVVIEDFEATSSQELTVSKGQTVEVLERPSSRPDWCLVRTLeqDNSPPQEGLVPSSILCI 62
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 1470-1605 3.21e-27

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 109.27  E-value: 3.21e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1470 LSMLEGFDENIESQGELILQESFQVWDPK-TLIRKGRERHLFLFEMSLVFSKEVKDSSGRSK--YLYKSKLFTSELGVTE 1546
Cdd:cd13241      1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSaGLLQKGKERRVFLFEQIIIFSEILGKKTQFSNpgYIYKNHIKVNKMSLEE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1547 HVEGDPCKFALWvGRTP-TSDNKIVLKASSIENKQDWIKHIREVIQERTVHLRgALKEPI 1605
Cdd:cd13241     81 NVDGDPLRFALK-SRDPnNPSETFILQAASPEVRQEWVDTINQILDTQRDFLK-ALQSPI 138
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
 2806-2876 1.90e-25

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 107.74  E-value: 1.90e-25
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14006      1 LGRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELC 71
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 567-783 3.59e-25

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 105.99  E-value: 3.59e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  567 QLCVFQQDVQQVLDWIENHGEAFLSkhTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIY 646
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSS--TDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  647 QAAHQLEDRIQDFVRRVEQRKILLDMSV---SFHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKRFgqqqqttlQV 723
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALdlqQFFRDADDLEQWLEEKEAALASEDLGKDLESVEELLKKH--------KE 150

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  724 TVNVIKEGEDLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEELFQERKIKLE 783
Cdd:cd00176    151 LEEELEAHEPRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLE 210
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 2806-2876 2.85e-24

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 104.66  E-value: 2.85e-24
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14115      1 IGRGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELM 71
I-set pfam07679
Immunoglobulin I-set domain;
2689-2780 4.31e-22

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 92.71  E-value: 4.31e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHnTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQ-PLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:pfam07679   79 AGEAEASAELTV 90
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
 69-204 5.53e-22

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 95.06  E-value: 5.53e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731    69 LKEKVAYLSGGR--DKRGGPILTFPARS--NHDRIRQEDLRRLISYLACIPSEE---VCKRGFTVIVDMRGSK-----WD 136
Cdd:smart00516    2 LELLKAYIPGGRgyDKDGRPVLIERAGRfdLKSVTLEELLRYLVYVLEKILQEEkktGGIEGFTVIFDLKGLSmsnpdLS 81

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731   137 SIKPLLKILQESFPCCIHIALIIKPDNFWQ---KQRTNFGSSKFEFETNMVSL---EGLTKVVDPSQLTPEFDG 204
Cdd:smart00516   82 VLRKILKILQDHYPERLGKVYIINPPWFFRvlwKIIKPFLDEKTREKIRFVGNdskEELLEYIDKEQLPEELGG 155
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
 1462-1598 2.02e-21

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270062  Cd Length: 136  Bit Score: 92.35  E-value: 2.02e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1462 KRANDAMHLSMLEGFDENIESQGELILQESFQVWDPktliRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSE 1541
Cdd:cd13242      5 RHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQG----RKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 1542 LGVTEHVEGDPCKFALWVgRTPTSDNKIVLKASSIENKQDWIKHIREVIQERTVHLR 1598
Cdd:cd13242     81 IGLTENVGDSGLKFEIWF-RRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 1475-1590 3.79e-21

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. 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: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 91.49  E-value: 3.79e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1475 GFDENIESQGELILQESFQVW------DPKTLIR-KGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEH 1547
Cdd:cd01227      4 GYDGNLGDLGKLLMQGSFNVWtehkkgHTKKLARfKPMQRHIFLYEKAVLFCKKRGENGEAPSYSYKNSLNTTAVGLTEN 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1907111731 1548 VEGDPCKFALWV-GRTPTsdnkIVLKASSIENKQDWIKHIREVI 1590
Cdd:cd01227     84 VKGDTKKFEIWLnGREEV----FIIQAPTPEIKAAWVKAIRQVL 123
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
 2143-2273 5.31e-21

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270062  Cd Length: 136  Bit Score: 91.20  E-value: 5.31e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2143 NDMMNVGRLQGFDGKIVAQGKLLLQDTFLVTDQDagllpRCKERRVFLFEQIVIFSEPLDKKKGFSMpgFLFKNSIKVSC 2222
Cdd:cd13242      8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGR-----KKCLRHVFLFEDLILFSKPKKTPGGKDV--YIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907111731 2223 LCLEENVESDPCKFALTSRTGDAVETFVLHSSSPSVRQTWIHEINQILENQ 2273
Cdd:cd13242     81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQ 131
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 908-1137 8.46e-19

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 87.50  E-value: 8.46e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  908 QLRHLQAEVKQVLGWIRNGESMLNAGLiTASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDMIRD 987
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSSTD-YGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  988 CAEKVASHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVlesleqeykreEDWCGGADKLGPNSETDHVTPMISKHLEQK 1067
Cdd:cd00176     80 RLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDL-----------EQWLEEKEAALASEDLGKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1068 EAFLKACTlarrNADVFLKYLHRNSVSMPGmvTHIKAPEQQVKNILNELFQRENRVLHYWTMRKRRLDQC 1137
Cdd:cd00176    149 KELEEELE----AHEPRLKSLNELAEELLE--EGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEA 212
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 2151-2271 5.44e-18

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 82.43  E-value: 5.44e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2151 LQGFDGKIVAQGKLLLQDTFLVTDQDAgLLPRCKERRVFLFEQIVIFSEPLDKKKGFSmpGFLFKNSIKVSCLCLEENVE 2230
Cdd:cd13240      2 LEGCDEDLDSLGEVILQDSFQVWDPKQ-LIRKGRERHVFLFELCLVFSKEVKDSNGKS--KYIYKSRLMTSEIGVTEHIE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1907111731 2231 SDPCKFAL-TSRTGDAVETFVLHSSSPSVRQTWIHEINQILE 2271
Cdd:cd13240     79 GDPCKFALwTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQ 120
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 341-566 1.02e-17

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 84.42  E-value: 1.02e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  341 QLRLFEQDAEKMFDWITHnKGLFLNSyTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIK 420
Cdd:cd00176      1 KLQQFLRDADELEAWLSE-KEELLSS-TDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  421 QIANQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKyMSNVDSWCKACGEV----DLPSELQDLEDAIHHHQGIYEHITL 496
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRD-ADDLEQWLEEKEAAlaseDLGKDLESVEELLKKHKELEEELEA 157

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  497 AysevSQDGKSLLDKLQRPLTPGSSDSLTasanyskavhHVLDVIHEVLHHQRQLENIWQHRKVRLHQRL 566
Cdd:cd00176    158 H----EPRLKSLNELAEELLEEGHPDADE----------EIEEKLEELNERWEELLELAEERQKKLEEAL 213
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 787-1014 1.71e-16

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 80.95  E-value: 1.71e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  787 QLRIFERDAidiiSDLESWNDELSQQMNDFDT-EDLTIAEQRLQHHADKALTMNNltfdviHQGQdllqyVNEVQASGvE 865
Cdd:cd00176      1 KLQQFLRDA----DELEAWLSEKEELLSSTDYgDDLESVEALLKKHEALEAELAA------HEER-----VEALNELG-E 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  866 LLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQVLGWIRNGESMLNAGLITaSSLQEAEQ 945
Cdd:cd00176     65 QLIEEGHPDAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAALASEDLG-KDLESVEE 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  946 LQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDM-IRDCAEKVASHWQQLMLKMEDRLKLVNASV 1014
Cdd:cd00176    144 LLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADEeIEEKLEELNERWEELLELAEERQKKLEEAL 213
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2688-2767 1.72e-16

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 76.45  E-value: 1.72e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNddHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVN 2767
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSG--STRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2696-2780 4.98e-16

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 75.23  E-value: 4.98e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  2696 SEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVNDMGSASSS 2775
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSG-STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1907111731  2776 ASLRV 2780
Cdd:smart00410   81 TTLTV 85
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
 2806-2875 9.05e-16

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 79.58  E-value: 9.05e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVN-KKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14103      1 LGRGKFGTVYRCVEKATGKELAAKFIKcRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEY 71
SEC14 cd00170
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
 74-204 2.98e-15

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 469559 [Multi-domain]  Cd Length: 156  Bit Score: 75.45  E-value: 2.98e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   74 AYLSGGRDKRGGPILTFPAR-SNHDRIRQEDLRRLISYL--ACIPSEEVCKRGFTVIVDMRGSKW------DSIKPLLKI 144
Cdd:cd00170     11 IGYLGGRDKEGRPVLVFRAGwDPPKLLDLEELLRYLVYLleKALRELEEQVEGFVVIIDLKGFSLsnlsdlSLLKKLLKI 90

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  145 LQESFPCCIHIALIIKPDNF----WQ------KQRTnfgSSKFEFETNmvSLEGLTKVVDPSQLTPEFDG 204
Cdd:cd00170     91 LQDHYPERLKKIYIVNAPWIfsalWKivkpflSEKT---RKKIVFLGS--DLEELLEYIDPDQLPKELGG 155
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
 2794-2877 3.07e-15

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 78.68  E-value: 3.07e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2794 DNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK-------RDQVTHELGILQNLQHPLLVSLLDTFETP 2866
Cdd:cd14105      1 ENVEDFYDIGEELGSGQFAVVKKCREKSTGLEYAAKFIKKRRSKasrrgvsREDIEREVSILRQVLHPNIITLHDVFENK 80

                           90
                   ....*....|.
gi 1907111731 2867 TSYVLVLEILR 2877
Cdd:cd14105     81 TDVVLILELVA 91
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 220-445 3.46e-15

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 77.10  E-value: 3.46e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  220 FEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKK--KVIKAPIEDLDLEGQKLLQriqssdsfpkknS 297
Cdd:cd00176      2 LQQFLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAelAAHEERVEALNELGEQLIE------------E 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  298 GSGNADlqnllpKVSTMLDRLHSTRQHLHQMWHVRKLKLDQCFQLRLFEQDAEKMFDWIThNKGLFLNSyTEIGTSHPHA 377
Cdd:cd00176     70 GHPDAE------EIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLE-EKEAALAS-EDLGKDLESV 141

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731  378 MELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQ-QIKQIANQLEQEWKAFAAALDERSTLLD 445
Cdd:cd00176    142 EELLKKHKELEEELEAHEPRLKSLNELAEELLEEGHPDADeEIEEKLEELNERWEELLELAEERQKKLE 210
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
 2805-2877 4.34e-15

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 77.90  E-value: 4.34e-15
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd05117      7 VLGRGSFGVVRLAVHKKTGEEYAVKIIDKKKLKSEDEEMlrrEIEILKRLDHPNIVKLYEVFEDDKNLYLVMELCT 82
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 2800-2874 5.06e-15

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 77.57  E-value: 5.06e-15
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731  2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK--RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKkdRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVME 77
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
 2794-2876 8.14e-15

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 77.37  E-value: 8.14e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2794 DNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK-------RDQVTHELGILQNLQHPLLVSLLDTFETP 2866
Cdd:cd14194      1 ENVDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKssrrgvsREDIEREVSILKEIQHPNVITLHEVYENK 80

                           90
                   ....*....|
gi 1907111731 2867 TSYVLVLEIL 2876
Cdd:cd14194     81 TDVILILELV 90
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 1472-1593 2.92e-14

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. 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: 270059  Cd Length: 125  Bit Score: 71.81  E-value: 2.92e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1472 MLEGFDENIESQGELILQESFQVWDPKTLIR---KGRERHLFLFEMSLVFSKEVKDSSGRSK-YLYKSKLFTSELGVTEH 1547
Cdd:cd13239      1 LIENYPAPLQALGEPIRQGHFTVWEEAPEVKtssRGHHRHVFLFKNCVVICKPKRDSRTDTVtYVFKNKMKLSDIDVKDT 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1907111731 1548 VEGDPCKFALWVGRTpTSDNKIVLKASSIENKQDWIKHIREvIQER 1593
Cdd:cd13239     81 VEGDDRSFGLWHEHR-GSVRKYTLQARSAIIKSSWLKDLRD-LQQR 124
Pkinase pfam00069
Protein kinase domain;
2800-2874 3.74e-14

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 74.20  E-value: 3.74e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNK---KLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKekiKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLE 78
SPEC smart00150
Spectrin repeats;
1143-1243 8.73e-14

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 69.67  E-value: 8.73e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1143 FERSAKQALEWIHDNGEfyLSTHTSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIKKCVT 1222
Cdd:smart00150    3 FLRDADELEAWLEEKEQ--LLASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731  1223 AVDKRYRDFSLRMEKYRTSLE 1243
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
SPEC smart00150
Spectrin repeats;
571-671 1.33e-13

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 68.90  E-value: 1.33e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   571 FQQDVQQVLDWIENHgEAFLSkHTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIYQAAH 650
Cdd:smart00150    3 FLRDADELEAWLEEK-EQLLA-SEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731   651 QLEDRIQDFVRRVEQRKILLD 671
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 2153-2273 1.34e-13

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. 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: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 69.92  E-value: 1.34e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2153 GFDGKIVAQGKLLLQDTFLV-TDQDAG---LLPRCK--ERRVFLFEQIVIFSepldKKKG--FSMPGFLFKNSIKVSCLC 2224
Cdd:cd01227      4 GYDGNLGDLGKLLMQGSFNVwTEHKKGhtkKLARFKpmQRHIFLYEKAVLFC----KKRGenGEAPSYSYKNSLNTTAVG 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1907111731 2225 LEENVESDPCKFALTsrTGDAVETFVLHSSSPSVRQTWIHEINQILENQ 2273
Cdd:cd01227     80 LTENVKGDTKKFEIW--LNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 2694-2780 2.05e-13

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 67.80  E-value: 2.05e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITWkgpehntLNNDDHYSISY--SDIGEATLKIIGVSTEDDGIYTCIAVNDMGS 2771
Cdd:cd20978      7 PEKNVVVKGGQDVTLPCQVTGVPQPKITW-------LHNGKPLQGPMerATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79


                   ....*....
gi 1907111731 2772 ASSSASLRV 2780
Cdd:cd20978     80 IYTETLLHV 88
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 1139-1246 5.07e-13

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 70.55  E-value: 5.07e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1139 QYVVFERSAKQALEWIHDNGEFYLSThtSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIK 1218
Cdd:cd00176      1 KLQQFLRDADELEAWLSEKEELLSST--DYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQ 78

                           90       100
                   ....*....|....*....|....*...
gi 1907111731 1219 KCVTAVDKRYRDFSLRMEKYRTSLEKAL 1246
Cdd:cd00176     79 ERLEELNQRWEELRELAEERRQRLEEAL 106
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
 2794-2876 5.19e-13

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 71.96  E-value: 5.19e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2794 DNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLM-------KRDQVTHELGILQNLQHPLLVSLLDTFETP 2866
Cdd:cd14195      1 SMVEDHYEMGEELGSGQFAIVRKCREKGTGKEYAAKFIKKRRLsssrrgvSREEIEREVNILREIQHPNIITLHDIFENK 80

                           90
                   ....*....|
gi 1907111731 2867 TSYVLVLEIL 2876
Cdd:cd14195     81 TDVVLILELV 90
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
 2795-2876 1.56e-12

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 70.37  E-value: 1.56e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2795 NFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKL-------MKRDQVTHELGILQNLQHPLLVSLLDTFETPT 2867
Cdd:cd14196      2 KVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRQsrasrrgVSREEIEREVSILRQVLHPNIITLHDVYENRT 81


                   ....*....
gi 1907111731 2868 SYVLVLEIL 2876
Cdd:cd14196     82 DVVLILELV 90
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 2703-2780 1.69e-12

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 65.11  E-value: 1.69e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2703 GETVVFRCRVCGRPKASITWKgpehntlNNDDHYSISYSDI-GEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd05725     12 DDSAEFQCEVGGDPVPTVRWR-------KEDGELPKGRYEIlDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2796-2876 1.80e-12

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 70.62  E-value: 1.80e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2796 FDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVnKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14085      1 LEDFFEIESELGRGATSVVYRCRQKGTQKPYAVKKL-KKTVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLEL 79


                   .
gi 1907111731 2876 L 2876
Cdd:cd14085     80 V 80
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 2703-2780 1.93e-12

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 65.17  E-value: 1.93e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2703 GETVVFRCRVCGRPKASITWKGPEHNTLNNDDhysISYSDIGeaTLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd04969     17 GGDVIIECKPKASPKPTISWSKGTELLTNSSR---ICILPDG--SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 676-907 5.07e-12

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 67.86  E-value: 5.07e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  676 FHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKR---FGQQQQTTLQVTVNVIKEGEDLIQQLRDSAissnktphns 752
Cdd:cd00176      5 FLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKheaLEAELAAHEERVEALNELGEQLIEEGHPDA---------- 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  753 siNHIETVLQQLDEAQSQMEELFQERKIKLELFLQLRIFERDAidiiSDLESWNDELSQQMNDFDT-EDLTIAEQRLQHH 831
Cdd:cd00176     75 --EEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDA----DDLEQWLEEKEAALASEDLgKDLESVEELLKKH 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731  832 ADKALTMNNltfdviHQGQdllqyVNEVQASGVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCV 907
Cdd:cd00176    149 KELEEELEA------HEPR-----LKSLNELAEELLEEGHPDADEEIEEKLEELNERWEELLELAEERQKKLEEAL 213
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 2689-2780 5.08e-12

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 64.36  E-value: 5.08e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITW--KGPEHNTLNNDDHYSIsYSDIGEATLKIIGVSTEDDGIYTCIAV 2766
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWykNGVPIDPSSIPGKYKI-ESEYGVHVLHIRRVTVEDSAVYSAVAK 79

                           90
                   ....*....|....
gi 1907111731 2767 NDMGSASSSASLRV 2780
Cdd:cd20951     80 NIHGEASSSASVVV 93
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 2794-2874 1.06e-11

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 68.03  E-value: 1.06e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2794 DNFDAFYS-EVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD---QVTHELGILQNLQ-HPLLVSLLDTFETPTS 2868
Cdd:cd14198      3 DNFNNFYIlTSKELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGQDcraEILHEIAVLELAKsNPRVVNLHEVYETTSE 82


                   ....*.
gi 1907111731 2869 YVLVLE 2874
Cdd:cd14198     83 IILILE 88
SPEC smart00150
Spectrin repeats;
910-1008 1.50e-11

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 63.12  E-value: 1.50e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   910 RHLQAEVKQVLGWIRNGESMLNAgLITASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDMIRDCA 989
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLLAS-EDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERL 79

                            90
                    ....*....|....*....
gi 1907111731   990 EKVASHWQQLMLKMEDRLK 1008
Cdd:smart00150   80 EELNERWEELKELAEERRQ 98
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
 2800-2874 1.59e-11

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 67.35  E-value: 1.59e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNK-KLM-KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14095      2 YDIGRVIGDGNFAVVKECRDKATDKEYALKIIDKaKCKgKEHMIENEVAILRRVKHPNIVQLIEEYDTDTELYLVME 78
SPEC smart00150
Spectrin repeats;
345-445 1.77e-11

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 62.73  E-value: 1.77e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   345 FEQDAEKMFDWITHNKGLFlnSYTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIKQIAN 424
Cdd:smart00150    3 FLRDADELEAWLEEKEQLL--ASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERLE 80

                            90       100
                    ....*....|....*....|.
gi 1907111731   425 QLEQEWKAFAAALDERSTLLD 445
Cdd:smart00150   81 ELNERWEELKELAEERRQKLE 101
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 2694-2780 2.05e-11

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 62.21  E-value: 2.05e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITWKgPEHNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGSAS 2773
Cdd:cd20973      3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWM-KDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                   ....*..
gi 1907111731 2774 SSASLRV 2780
Cdd:cd20973     82 CSAELTV 88
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 450-671 3.17e-11

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 65.54  E-value: 3.17e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  450 FHQKAEKYMSNVDSWCKACGEVDLPSELQDLEDAIHHHQGIYEHITLAYSEVSQdgkslLDKLqrpltpgsSDSLTASAN 529
Cdd:cd00176      5 FLRDADELEAWLSEKEELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEA-----LNEL--------GEQLIEEGH 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  530 YSKAVHHvlDVIHEVLHHQRQLENIWQHRKVRLHQRLQLCVFQQDVQQVLDWIENHGEAFLSkhTGVGKSLHRARALQKR 609
Cdd:cd00176     72 PDAEEIQ--ERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLEQWLEEKEAALAS--EDLGKDLESVEELLKK 147

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731  610 HEDFEEVAQNTYTNADKLLEAAEQLAQTGECD-PEEIYQAAHQLEDRIQDFVRRVEQRKILLD 671
Cdd:cd00176    148 HKELEEELEAHEPRLKSLNELAEELLEEGHPDaDEEIEEKLEELNERWEELLELAEERQKKLE 210
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 2805-2874 6.18e-11

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 65.73  E-value: 6.18e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD---QVTHELGILQNLQ-HPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14197     16 ELGRGKFAVVRKCVEKDSGKEFAAKFMRKRRKGQDcrmEIIHEIAVLELAQaNPWVINLHEVYETASEMILVLE 89
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2706-2775 1.22e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 59.65  E-value: 1.22e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2706 VVFRCRVCGRPKASITWKGPehNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSS 2775
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKN--GKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 2798-2875 1.45e-10

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 64.53  E-value: 1.45e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2798 AFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14107      2 SVYEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILEL 79
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 1449-1592 1.76e-10

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 61.60  E-value: 1.76e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1449 EIKDGLEVMLSVPKRAND-------AMHL----SMLEGFDE-NIESQGELILQESFqvwdpkTLIRKGRERHLFLFEMSL 1516
Cdd:cd13243      3 VVEEALDTMTQVAWHINDmkrkhehAVRVqeiqSLLDGWEGpELTTYGDLVLEGTF------RMAGAKNERLLFLFDKML 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 1517 VFSKEVKDSSgrskYLYKSKLFTSELGVTEHVEGDPCKFalWVGRTPTSDNKIVLKASSIENKQDWIKHIREVIQE 1592
Cdd:cd13243     77 LITKKREDGI----LQYKTHIMCSNLMLSESIPKEPLSF--QVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILE 146
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
 2806-2874 1.81e-10

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 64.08  E-value: 1.81e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14003      8 LGEGSFGKVKLARHKLTGEKVAIKIIDKSKLKEEIEEKikrEIEIMKLLNHPNIIKLYEVIETENKIYLVME 79
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 2694-2780 2.41e-10

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 59.44  E-value: 2.41e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYsiSYSDIGEaTLKIIGVSTEDDGIYTCIAVNDM-GSA 2772
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRY--IVRENGT-TLTIRNIRRSDMGIYLCIASNGVpGSV 84


                   ....*...
gi 1907111731 2773 SSSASLRV 2780
Cdd:cd20970     85 EKRITLQV 92
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 2793-2874 2.87e-10

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 63.52  E-value: 2.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2793 KDNFDAFYS-EVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQ---VTHELGIL-QNLQHPLLVSLLDTFETPT 2867
Cdd:cd14106      2 TENINEVYTvESTPLGRGKFAVVRKCIHKETGKEYAAKFLRKRRRGQDCrneILHEIAVLeLCKDCPRVVNLHEVYETRS 81


                   ....*..
gi 1907111731 2868 SYVLVLE 2874
Cdd:cd14106     82 ELILILE 88
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 2689-2780 2.91e-10

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 59.05  E-value: 2.91e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHySISYSDIGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAH-KMLVRENGRHSLIIEPVTKRDAGIYTCIARNR 79

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:cd05744     80 AGENSFNAELVV 91
CRAL_TRIO_2 pfam13716
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
 84-211 4.30e-10

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.


Pssm-ID: 463965 [Multi-domain]  Cd Length: 140  Bit Score: 60.03  E-value: 4.30e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   84 GGPILTFPARS-NHDRIRQEDLRRLISYLACIPSEEVCKRGFTVIVDMRGSKWDS------IKPLLKILQESFPCCIHIA 156
Cdd:pfam13716    1 GRPVLVFISKLlPSRPASLDDLDRLLFYLLKTLSEKLKGKPFVVVVDHTGVTSENfpslsfLKKAYDLLPRAFKKNLKAV 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  157 LIIKPDNFWQKQ----RTNFGSSKFEFETNMVS-LEGLTKVVDPSQLTPEFDGCLEYNHE 211
Cdd:pfam13716   81 YVVHPSTFLRTFlktlGSLLGSKKLRKKVHYVSsLSELWEGIDREQLPTELPGVLSYDEE 140
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2806-2875 1.61e-09

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 61.23  E-value: 1.61e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKR--DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14083     11 LGTGAFSEVVLAEDKATGKLVAIKCIDKKALKGkeDSLENEIAVLRKIKHPNIVQLLDIYESKSHLYLVMEL 82
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 2697-2780 1.63e-09

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 56.74  E-value: 1.63e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2697 EVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSIsysdIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSA 2776
Cdd:cd20952      8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITT----LENGSLQIKGAEKSDTGEYTCVALNLSGEATWSA 83


                   ....
gi 1907111731 2777 SLRV 2780
Cdd:cd20952     84 VLDV 87
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
 2806-2874 2.36e-09

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 60.70  E-value: 2.36e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFV-----NKKLmkRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14009      1 IGRGSFATVWKGRHKQTGEVVAIKEIsrkklNKKL--QENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLE 72
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 2706-2778 8.78e-09

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 54.89  E-value: 8.78e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2706 VVFRCRVCGRPKASITWkgpehnTLNND-----DHYSIsysdIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASL 2778
Cdd:cd05723     15 IVFECEVTGKPTPTVKW------VKNGDvvipsDYFKI----VKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
 2799-2876 1.03e-08

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 58.75  E-value: 1.03e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2799 FYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKL-MKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14114      3 HYDILEELGTGAFGVVHRCTERATGNNFAAKFIMTPHeSDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFL 81
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 2689-2780 1.06e-08

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 54.72  E-value: 1.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:cd05893     81 QGRISCTGRLMV 92
IgI_SALM5_like cd05764
Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; ...
 2703-2780 1.14e-08

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409421 [Multi-domain]  Cd Length: 88  Bit Score: 54.40  E-value: 1.14e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2703 GETVVFRCRVCGRPKASITWKGPEHNTLNNDDHySISYSDigeATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd05764     15 GQRATLRCKARGDPEPAIHWISPEGKLISNSSR-TLVYDN---GTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
 2806-2877 1.25e-08

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 58.81  E-value: 1.25e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLM--KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14185      8 IGDGNFAVVKECRHWNENQEYAMKIIDKSKLkgKEDMIESEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVR 81
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
 2806-2876 1.37e-08

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 58.43  E-value: 1.37e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK-RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14192     12 LGGGRFGQVHKCTELSTGLTLAAKIIKVKGAKeREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYV 83
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 2689-2780 1.50e-08

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 54.39  E-value: 1.50e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:cd05892     81 AGVVSCNARLDV 92
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
 1479-1592 1.64e-08

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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: 270134  Cd Length: 114  Bit Score: 55.05  E-value: 1.64e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1479 NIESQGELILQESFQVWDPKTlirKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEHvEGDPCKFALW 1558
Cdd:cd13325      2 NIHKLGRLLRHDWFTVTDGEG---KAKERYLFLFKSRILITKVRRISEDRSVFILKDIIRLPEVNVKQH-PDDERTFELQ 77

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1907111731 1559 VGRTPTSDNKIVLKASSIENKQDWIKHIREVIQE 1592
Cdd:cd13325     78 PKLPAFGILPIDFKAHKDEIKDYWLNEIEEYAND 111
CRAL_TRIO pfam00650
CRAL/TRIO domain;
79-204 1.69e-08

CRAL/TRIO domain;


Pssm-ID: 459890 [Multi-domain]  Cd Length: 151  Bit Score: 56.11  E-value: 1.69e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   79 GRDKRGGPILTF-PARSNHDRIRQEDLRRLISYLACI---PSEEVCKRGFTVIVDMRGSK--------WDSIKPLLKILQ 146
Cdd:pfam00650    8 GRDKEGRPVLYLrLGRHDPKKSSEEELVRFLVLVLERallLMPEGQVEGLTVIIDLKGLSlsnmdwwsISLLKKIIKILQ 87

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731  147 ESFPCCIHIALIIKPD---NFWQKQRTNFGS----SKFEFeTNMVSLEGLTKVVDPSQLTPEFDG 204
Cdd:pfam00650   88 DNYPERLGKILIVNAPwifNTIWKLIKPFLDpktrEKIVF-LKNSNEEELEKYIPPEQLPKEYGG 151
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
 2800-2874 1.81e-08

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 58.26  E-value: 1.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNK---KLMKR--DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14098      2 YQIIDRLGSGTFAEVKKAVEVETGKMRAIKQIVKrkvAGNDKnlQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVME 81
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2688-2780 2.02e-08

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 53.73  E-value: 2.02e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPeFVIPLSEVTCETGETVVFRCRVCGRPKASITW-KG----PehntlnnDDHYSISYSDigeATLKIIGVST-EDDGIY 2761
Cdd:cd20958      1 PP-FIRPMGNLTAVAGQTLRLHCPVAGYPISSITWeKDgrrlP-------LNHRQRVFPN---GTLVIENVQRsSDEGEY 69

                           90       100
                   ....*....|....*....|
gi 1907111731 2762 TCIAVNDMG-SASSSASLRV 2780
Cdd:cd20958     70 TCTARNQQGqSASRSVFVKV 89
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 2693-2778 2.13e-08

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 53.74  E-value: 2.13e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2693 IPLSEVTCETGETVVFRCRV-CGRPKASITWKGpEHNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGS 2771
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSK-EGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79


                   ....*..
gi 1907111731 2772 ASSSASL 2778
Cdd:pfam00047   80 ATLSTSL 86
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 2688-2780 2.41e-08

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 53.74  E-value: 2.41e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITW--KGPE-HNTLNnddhysISYSDIGEATLKIIGVSTEDD-GIYTC 2763
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWfcEGKElQNSPD------IQIHQEGDLHSLIIAEAFEEDtGRYSC 74

                           90
                   ....*....|....*..
gi 1907111731 2764 IAVNDMGSASSSASLRV 2780
Cdd:cd20972     75 LATNSVGSDTTSAEIFV 91
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
 2802-2874 2.97e-08

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 57.26  E-value: 2.97e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 2802 EVAEL-GRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVT---HELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14002      4 HVLELiGEGSFGKVYKGRRKYTGQVVALKFIPKRGKSEKELRnlrQEIEILRKLNHPNIIEMLDSFETKKEFVVVTE 80
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2805-2876 3.05e-08

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 57.82  E-value: 3.05e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVN-KKLMKRD--QVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14086      8 ELGKGAFSVVRRCVQKSTGQEFAAKIINtKKLSARDhqKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLV 82
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2699-2780 3.64e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 52.92  E-value: 3.64e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2699 TCETGETVVFRCRVCGRPKASITW-KGPEHntLNNDDHYSIsysdIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSAS 2777
Cdd:cd20957     12 TVDFGRTAVFNCSVTGNPIHTVLWmKDGKP--LGHSSRVQI----LSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAE 85


                   ...
gi 1907111731 2778 LRV 2780
Cdd:cd20957     86 LKL 88
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2688-2780 4.27e-08

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 52.95  E-value: 4.27e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKgPEHNTLNNDDHYSIS-Y-SDIGEAT--LKIIGVSTEDDGIYTC 2763
Cdd:cd20956      1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWT-LDGFPIPESPRFRVGdYvTSDGDVVsyVNISSVRVEDGGEYTC 79

                           90
                   ....*....|....*..
gi 1907111731 2764 IAVNDMGSASSSASLRV 2780
Cdd:cd20956     80 TATNDVGSVSHSARINV 96
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 1469-1593 4.63e-08

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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: 269931  Cd Length: 138  Bit Score: 54.19  E-value: 4.63e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1469 HLSMLEGFDENIES-QGELILQESFQVWDPKTL--IRKGR--ERHLFLFEMSLVFSKevKDSSGRSKYLYKSKLFTSELG 1543
Cdd:cd01224      3 NLEKLAAWQSTVEGwEGEDLSDRSSELIHSGELtkISAGRaqERTFFLFDHQLVYCK--KDLLRRKNYIYKGRIDTDNME 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 1544 V------TEHVEGDPCKFALWVGRtpTSDNK-IVLKASSIENKQDWIKHIREviqER 1593
Cdd:cd01224     81 IedlpdgKDDESGVTVKNAWKIYN--ASKNKwYVLCAKSAEEKQRWLEAFAE---ER 132
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 908-999 7.21e-08

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 52.71  E-value: 7.21e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  908 QLRHLQAEVKQVLGWIRNGESMLNAGLItASSLQEAEQLQREHEQFQHAIEkTHQSALQ-VQQKAEAMLQANHYDMDMIR 986
Cdd:pfam00435    2 LLQQFFRDADDLESWIEEKEALLSSEDY-GKDLESVQALLKKHKALEAELA-AHQDRVEaLNELAEKLIDEGHYASEEIQ 79

                           90
                   ....*....|...
gi 1907111731  987 DCAEKVASHWQQL 999
Cdd:pfam00435   80 ERLEELNERWEQL 92
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2797-2876 7.73e-08

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 56.44  E-value: 7.73e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2797 DAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLM--KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14169      2 NSVYELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKALrgKEAMVENEIAVLRRINHENIVSLEDIYESPTHLYLAME 81


                   ..
gi 1907111731 2875 IL 2876
Cdd:cd14169     82 LV 83
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
 2689-2780 7.94e-08

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 52.55  E-value: 7.94e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEH---NTLNNDDHY--SISYSDIGEatLKIIGVSTEDDGIYTC 2763
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPgkeNLIMRPNHVrgNVVVTNIGQ--LVIYNAQPQDAGLYTC 78

                           90
                   ....*....|....*..
gi 1907111731 2764 IAVNDMGSASSSASLRV 2780
Cdd:cd05765     79 TARNSGGLLRANFPLSV 95
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
 2806-2877 8.81e-08

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 56.16  E-value: 8.81e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLM--KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14183     14 IGDGNFAVVKECVERSTGREYALKIINKSKCrgKEHMIQNEVSILRRVKHPNIVLLIEEMDMPTELYLVMELVK 87
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 2688-2780 1.01e-07

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 51.87  E-value: 1.01e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSIsysDIGEATLKIIGVSTEDDGIYTCIAVN 2767
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTC---EAGVGELHIQDVLPEDHGTYTCLAKN 77

                           90
                   ....*....|...
gi 1907111731 2768 DMGSASSSASLRV 2780
Cdd:cd20976     78 AAGQVSCSAWVTV 90
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
 2806-2874 1.20e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 55.70  E-value: 1.20e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK-RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14190     12 LGGGKFGKVHTCTEKRTGLKLAAKVINKQNSKdKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFME 81
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 2800-2875 1.23e-07

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 55.69  E-value: 1.23e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14110      5 YAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEEL 80
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1505-1590 1.26e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 52.18  E-value: 1.26e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1505 RERHLFLFEMSLVFSKevkDSSGRSKYLYKSKLFTSELGVTEHVEGD----PCKFALWVGrTPTSDNKIVLKASSIENKQ 1580
Cdd:pfam00169   19 KKRYFVLFDGSLLYYK---DDKSGKSKEPKGSISLSGCEVVEVVASDspkrKFCFELRTG-ERTGKRTYLLQAESEEERK 94

                           90
                   ....*....|
gi 1907111731 1581 DWIKHIREVI 1590
Cdd:pfam00169   95 DWIKAIQSAI 104
SPEC smart00150
Spectrin repeats;
221-337 1.39e-07

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 51.95  E-value: 1.39e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   221 EEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKKKV--IKAPIEDLDLEGQKLLQriqssdsfpkknSG 298
Cdd:smart00150    1 QQFLRDADELEAWLEEKEQLLASEDLGKDLESVEALLKKHEAFEAELeaHEERVEALNELGEQLIE------------EG 68

                            90       100       110
                    ....*....|....*....|....*....|....*....
gi 1907111731   299 SGNAdlqnllPKVSTMLDRLHSTRQHLHQMWHVRKLKLD 337
Cdd:smart00150   69 HPDA------EEIEERLEELNERWEELKELAEERRQKLE 101
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 2800-2876 1.48e-07

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 55.91  E-value: 1.48e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRF-AVVKKCDQKGTKRAVATKFVNK--------KLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYV 2870
Cdd:cd14096      3 YRLINKIGEGAFsNVYKAVPLRNTGKPVAIKVVRKadlssdnlKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYY 82


                   ....*.
gi 1907111731 2871 LVLEIL 2876
Cdd:cd14096     83 IVLELA 88
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 2806-2874 1.51e-07

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 55.22  E-value: 1.51e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLM-KRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05123      1 LGKGSFGKVLLVRKKDTGKLYAMKVLRKKEIiKRKEVEHtlnERNILERVNHPFIVKLHYAFQTEEKLYLVLD 73
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
 2806-2877 1.57e-07

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 55.42  E-value: 1.57e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLM--KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14184      9 IGDGNFAVVKECVERSTGKEFALKIIDKAKCcgKEHLIENEVSILRRVKHPNIIMLIEEMDTPAELYLVMELVK 82
IgI_Lingo-1 cd20969
Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing ...
 2697-2780 1.57e-07

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409561  Cd Length: 92  Bit Score: 51.62  E-value: 1.57e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2697 EVTCETGETVVFRCRVCGRPKASITWKGPEHNTLN---NDDHYSISysdigEATLKIIGVSTEDDGIYTCIAVNDMGSAS 2773
Cdd:cd20969     11 QVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSaksNGRLTVFP-----DGTLEVRYAQVQDNGTYLCIAANAGGNDS 85


                   ....*..
gi 1907111731 2774 SSASLRV 2780
Cdd:cd20969     86 MPAHLHV 92
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 1662-1712 1.70e-07

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: 49.77  E-value: 1.70e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVRTTDRSpaaEGLVP 1712
Cdd:cd00174      3 RALYDYEAQDDDELSFKKGDIITVLEKDDD--GWWEGELNGGR---EGLFP 48
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1483-1591 1.90e-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: 51.40  E-value: 1.90e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  1483 QGELILQEsfqvwdpKTLIRKGRERHLFLFEMSLVFSKevkDSSGRSKYLYKSKLFTSELGVTEHVEGD----PCKFALW 1558
Cdd:smart00233    4 EGWLYKKS-------GGGKKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDPDsskkPHCFEIK 73

                            90       100       110
                    ....*....|....*....|....*....|...
gi 1907111731  1559 VGRTPTsdnkIVLKASSIENKQDWIKHIREVIQ 1591
Cdd:smart00233   74 TSDRKT----LLLQAESEEEREKWVEALRKAIA 102
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
 2799-2876 2.03e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 55.01  E-value: 2.03e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2799 FYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK-RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14191      3 FYDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFKAYSAKeKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMV 81
Ig3_L1-CAM_like cd05731
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar ...
 2694-2780 2.19e-07

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.


Pssm-ID: 409394 [Multi-domain]  Cd Length: 83  Bit Score: 50.87  E-value: 2.19e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITWKgPEHNTLNNDdhySISYSDIGEaTLKIIGVSTEDDGIYTCIAVNDMGSAS 2773
Cdd:cd05731      1 SESSTMVLRGGVLLLECIAEGLPTPDIRWI-KLGGELPKG---RTKFENFNK-TLKIENVSEADSGEYQCTASNTMGSAR 75


                   ....*..
gi 1907111731 2774 SSASLRV 2780
Cdd:cd05731     76 HTISVTV 82
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1969-2135 2.27e-07

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 56.82  E-value: 2.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1969 RRHYVLQELVETERDYVRDLGCVVEGYMALMKE-DGVPDDMKGK-DKIVFGNIHQIYDWHRDFfLGELEK--CLED-PEK 2043
Cdd:COG5422    484 KRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEEsNIIPENARRNfIKHVFANINEIYAVNSKL-LKALTNrqCLSPiVNG 562

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2044 LGSLFVKHERRLHMYIVYCQNKP------KSEHIVSEYIDTFFED-LKQRLGHRLQLTDLLIKPVQRIMKYQLLLKDFLK 2116
Cdd:COG5422    563 IADIFLDYVPKFEPFIKYGASQPyakyefEREKSVNPNFARFDHEvERLDESRKLELDGYLTKPTTRLARYPLLLEEVLK 642

                          170
                   ....*....|....*....
gi 1907111731 2117 YSKKASLDTSELEKAVEVM 2135
Cdd:COG5422    643 FTDPDNPDTEDIPKVIDML 661
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 1662-1713 2.44e-07

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: 49.46  E-value: 2.44e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1907111731  1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVRTTDRspaAEGLVPC 1713
Cdd:smart00326    6 RALYDYTAQDPDELSFKKGDIITVLEKSDD--GWWKGRLGRG---KEGLFPS 52
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
 2806-2874 2.50e-07

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 54.58  E-value: 2.50e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKR----DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14079     10 LGVGSFGKVKLAEHELTGHKVAVKILNRQKIKSldmeEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVME 82
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 2688-2780 3.10e-07

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 50.70  E-value: 3.10e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEV--TCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYsDIGEATlkIIGVSTEDDGIYTCIA 2765
Cdd:cd05730      1 PPTIRARQSEVnaTANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNE-DGSEMT--ILDVDKLDEAEYTCIA 77

                           90
                   ....*....|....*
gi 1907111731 2766 VNDMGSASSSASLRV 2780
Cdd:cd05730     78 ENKAGEQEAEIHLKV 92
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1501-1586 3.28e-07

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: 50.62  E-value: 3.28e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1501 IRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKsklFTSELGVTEHVEGD-PCKFALWVgrtpTSDNKIVLKASSIENK 1579
Cdd:cd00821     13 LKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIP---LSGILEVEEVSPKErPHCFELVT----PDGRTYYLQADSEEER 85


                   ....*..
gi 1907111731 1580 QDWIKHI 1586
Cdd:cd00821     86 QEWLKAL 92
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 2689-2781 3.71e-07

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 50.43  E-value: 3.71e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITW-KGPEHNTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVN 2767
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWfRDGQVISTSTLPGVQISFSD-GRAKLSIPAVTKANSGRYSLTATN 79

                           90
                   ....*....|....
gi 1907111731 2768 DMGSASSSASLRVL 2781
Cdd:cd20974     80 GSGQATSTAELLVL 93
Ig3_Peroxidasin cd05745
Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 2703-2780 4.73e-07

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143222 [Multi-domain]  Cd Length: 74  Bit Score: 49.55  E-value: 4.73e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2703 GETVVFRCRVCGRPKASITW-KGpeHNTLNNDDHYSIsysdIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWtKG--GSQLSVDRRHLV----LSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 1143-1243 6.31e-07

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 50.01  E-value: 6.31e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1143 FERSAKQALEWIHDNGEFYLSThtSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIKKCVT 1222
Cdd:pfam00435    6 FFRDADDLESWIEEKEALLSSE--DYGKDLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQERLE 83

                           90       100
                   ....*....|....*....|.
gi 1907111731 1223 AVDKRYRDFSLRMEKYRTSLE 1243
Cdd:pfam00435   84 ELNERWEQLLELAAERKQKLE 104
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 2801-2877 6.55e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 53.84  E-value: 6.55e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2801 SEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLmkrdQVTHELGILQNLQ-HPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14092      9 LREEALGDGSFSVCRKCVHKKTGQEFAVKIVSRRL----DTSREVQLLRLCQgHPNIVKLHEVFQDELHTYLVMELLR 82
SPEC smart00150
Spectrin repeats;
676-783 6.74e-07

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 50.02  E-value: 6.74e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731   676 FHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKR---FGQQQQTTLQVTVNVIKEGEDLIQQlrdsaissnktpHNS 752
Cdd:smart00150    3 FLRDADELEAWLEEKEQLLASEDLGKDLESVEALLKKheaFEAELEAHEERVEALNELGEQLIEE------------GHP 70

                            90       100       110
                    ....*....|....*....|....*....|.
gi 1907111731   753 SINHIETVLQQLDEAQSQMEELFQERKIKLE 783
Cdd:smart00150   71 DAEEIEERLEELNERWEELKELAEERRQKLE 101
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
 2806-2874 7.53e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 53.38  E-value: 7.53e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK-RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14193     12 LGGGRFGQVHKCEEKSSGLKLAAKIIKARSQKeKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVME 81
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
 1660-1713 7.77e-07

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212698 [Multi-domain]  Cd Length: 54  Bit Score: 48.03  E-value: 7.77e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 1660 LTVVIHDFTACNSNELTIRRGQTVEVLErphDKPDWCLVRTtdrSPAAEGLVPC 1713
Cdd:cd11764      1 YVRVLYDFTARNSKELSVLKGEYLEVLD---DSRQWWKVRN---SRGQVGYVPH 48
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
 2805-2877 8.08e-07

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 53.41  E-value: 8.08e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKlmKRDqVTHELGILQNL-QHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14091      7 EIGKGSYSVCKRCIHKATGKEYAVKIIDKS--KRD-PSEEIEILLRYgQHPNIITLRDVYDDGNSVYLVTELLR 77
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
 2806-2874 9.35e-07

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 52.76  E-value: 9.35e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2806 LGRGRFAVV-KKCDQKGTKRAVATKFVNKKLMKRDQ--VTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14120      1 IGHGAFAVVfKGRHRKKPDLPVAIKCITKKNLSKSQnlLGKEIKILKELSHENVVALLDCQETSSSVYLVME 72
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 2803-2874 9.73e-07

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 53.39  E-value: 9.73e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 2803 VAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLM-KRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05574      6 IKLLGKGDVGRVYLVRLKGTGKLFAMKVLDKEEMiKRNKVKRvltEREILATLDHPFLPTLYASFQTSTHLCFVMD 81
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
 1662-1713 1.04e-06

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


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 47.63  E-value: 1.04e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERphDKPDWCLVRTTDRspaaEGLVPC 1713
Cdd:cd11856      3 VAIADYEAQGDDEISLQEGEVVEVLEK--NDSGWWYVRKGDK----EGWVPA 48
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1280-1457 1.05e-06

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 54.90  E-value: 1.05e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1280 HELNEEKRKSARRKEFIMAELIQTEKAYVRDLRECMDTY---LWEMTsgveeIPPGIVNKELI--IFGNMQEIYEFhNNI 1354
Cdd:COG5422    472 KEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWikpLEESN-----IIPENARRNFIkhVFANINEIYAV-NSK 545

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1355 FLKELEK---YEQLPEDVGHCFVTWADKFQMYVTYCKNKPDSTQLIlEHAGS-------YFDEIQ-----QRHGlansIS 1419
Cdd:COG5422    546 LLKALTNrqcLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEF-EREKSvnpnfarFDHEVErldesRKLE----LD 620

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1907111731 1420 SYLIKPVQRITKYQLLLKELLTCCEEGKGEIKDGLEVM 1457
Cdd:COG5422    621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVI 658
IgI_1_NCAM-1 cd05865
First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); member of the ...
 2703-2775 1.36e-06

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1). NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-nonNCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409451  Cd Length: 97  Bit Score: 48.88  E-value: 1.36e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2703 GETVVFRCRVCGRPKAS-ITWKGPEHNTLN-NDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSS 2775
Cdd:cd05865     15 GESKFFLCQVAGEAKDKdISWFSPNGEKLTpNQQRISVVRNDDYSSTLTIYNANIDDAGIYKCVVSNEDEGESEA 89
IgI_M-protein_C cd05891
C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily ...
 2698-2770 1.53e-06

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.


Pssm-ID: 143299  Cd Length: 92  Bit Score: 48.75  E-value: 1.53e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2698 VTCETGETVVFRCRVCGRPKASITWKGPEHNtLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMG 2770
Cdd:cd05891     11 VTIMEGKTLNLTCTVFGNPDPEVIWFKNDQD-IELSEHYSVKLEQGKYASLTIKGVTSEDSGKYSINVKNKYG 82
Ig5_Contactin-1 cd05852
Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth ...
 2703-2780 1.78e-06

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409438  Cd Length: 89  Bit Score: 48.46  E-value: 1.78e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2703 GETVVFRCRVCGRPKASITW-KGPEhnTLNNDDHYSIsYSDigeATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd05852     17 GGRVIIECKPKAAPKPKFSWsKGTE--LLVNNSRISI-WDD---GSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2793-2876 1.79e-06

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 52.34  E-value: 1.79e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2793 KDNFDafYSEVaeLGRGRFAVVKKCDQKGTKRAVATKFVNKKLM--KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYV 2870
Cdd:cd14167      2 RDIYD--FREV--LGTGAFSEVVLAEEKRTQKLVAIKCIAKKALegKETSIENEIAVLHKIKHPNIVALDDIYESGGHLY 77


                   ....*.
gi 1907111731 2871 LVLEIL 2876
Cdd:cd14167     78 LIMQLV 83
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
 2797-2874 2.11e-06

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 51.93  E-value: 2.11e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2797 DAFYSEVAELGRGRFAVV-KKCDQKGTKRAVATKFVNKKLMKRDQVT--HELGILQNLQHPLLVSLLDTFETPTSYVLVL 2873
Cdd:cd14201      5 DFEYSRKDLVGHGAFAVVfKGRHRKKTDWEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVM 84


                   .
gi 1907111731 2874 E 2874
Cdd:cd14201     85 E 85
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
 2806-2877 2.50e-06

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 51.64  E-value: 2.50e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLM---KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14082     11 LGSGQFGIVYGGKHRKTGRDVAIKVIDKLRFptkQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKLH 85
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
 2805-2877 2.99e-06

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 51.45  E-value: 2.99e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKL----MKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd05581      8 PLGEGSYSTVVLAKEKETGKEYAIKVLDKRHiikeKKVKYVTIEKEVLSRLAHPGIVKLYYTFQDESKLYFVLEYAP 84
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 341-444 3.08e-06

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 48.08  E-value: 3.08e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  341 QLRLFEQDAEKMFDWIThNKGLFLNSyTEIGTSHPHAMELQTQHNHFAMNcMNVY-VNINRIMSVANRLVESGHYASQQI 419
Cdd:pfam00435    2 LLQQFFRDADDLESWIE-EKEALLSS-EDYGKDLESVQALLKKHKALEAE-LAAHqDRVEALNELAEKLIDEGHYASEEI 78

                           90       100
                   ....*....|....*....|....*
gi 1907111731  420 KQIANQLEQEWKAFAAALDERSTLL 444
Cdd:pfam00435   79 QERLEELNERWEQLLELAAERKQKL 103
IgI_1_NCAM-1_like cd04977
First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar ...
 2693-2775 3.25e-06

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-nonNCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409366  Cd Length: 95  Bit Score: 47.63  E-value: 3.25e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2693 IPLSEVTCETGETVVFRCRVCGRPKaSITWKGPE-HNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGS 2771
Cdd:cd04977      5 IIPSYAEISVGESKFFLCKVSGDAK-NINWVSPNgEKVLTKHGNLKVVNHGSVLSSLTIYNANINDAGIYKCVATNGKGT 83


                   ....
gi 1907111731 2772 ASSS 2775
Cdd:cd04977     84 ESEA 87
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
 2798-2875 3.27e-06

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 51.38  E-value: 3.27e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2798 AFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14087      1 AKYDIKALIGRGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMEL 78
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
 2806-2877 3.64e-06

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 51.24  E-value: 3.64e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKR---------DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14084     14 LGSGACGEVKLAYDKSTCKKVAIKIINKRKFTIgsrreinkpRNIETEIEILKKLSHPCIIKIEDFFDAEDDYYIVLELM 93


                   .
gi 1907111731 2877 R 2877
Cdd:cd14084     94 E 94
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
 2807-2876 4.22e-06

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 51.10  E-value: 4.22e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2807 GRGRFAVVKKCDQKGTKRAVATKFVNK-KLMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd05578      9 GKGSFGKVCIVQKKDTKKMFAMKYMNKqKCIEKDSVRNvlnELEILQELEHPFLVNLWYSFQDEEDMYMVVDLL 82
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 2689-2780 4.46e-06

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 47.40  E-value: 4.46e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKgPEHNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQ-LDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNR 79

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:cd20990     80 AGQNSFNLELVV 91
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 1662-1713 4.87e-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: 4.87e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVRTTDRSpaaEGLVPC 1713
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSED--GWWKGRNKGGK---EGLIPS 47
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
 2794-2874 5.92e-06

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 50.87  E-value: 5.92e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2794 DNFDafysEVAELGRGRFAVVKKCDQKGTKRAVATKFVNK-KLMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSY 2869
Cdd:cd14209      1 DDFD----RIKTLGTGSFGRVMLVRHKETGNYYAMKILDKqKVVKLKQVEHtlnEKRILQAINFPFLVKLEYSFKDNSNL 76


                   ....*
gi 1907111731 2870 VLVLE 2874
Cdd:cd14209     77 YMVME 81
IgI_Myomesin_like_C cd05737
C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of ...
 2698-2780 6.22e-06

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.


Pssm-ID: 319300  Cd Length: 92  Bit Score: 46.82  E-value: 6.22e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2698 VTCETGETVVFRCRVCGRPKASITWkgpehntLNND------DHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGS 2771
Cdd:cd05737     11 VTIMEGKTLNLTCNVWGDPPPEVSW-------LKNDqalaflDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYGS 83


                   ....*....
gi 1907111731 2772 ASSSASLRV 2780
Cdd:cd05737     84 ETSDVTVSV 92
IgI_APEG-1_like cd20975
Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and ...
 2689-2780 6.26e-06

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409567  Cd Length: 91  Bit Score: 47.08  E-value: 6.26e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEG-GLCRLRILAAERGDAGFYTCKAVNE 79

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:cd20975     80 YGARQCEARLEV 91
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
 2800-2876 7.18e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 50.65  E-value: 7.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATK--FVNKKLMKRDQVT----HELGILQNLQHPLLVSLLDTFETPTSYVLVL 2873
Cdd:cd07841      2 YEKGKKLGEGTYAVVYKARDKETGRIVAIKkiKLGERKEAKDGINftalREIKLLQELKHPNIIGLLDVFGHKSNINLVF 81


                   ...
gi 1907111731 2874 EIL 2876
Cdd:cd07841     82 EFM 84
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
 2806-2874 9.37e-06

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 49.78  E-value: 9.37e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKR----DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14007      8 LGKGKFGNVYLAREKKSGFIVALKVISKSQLQKsgleHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILE 80
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 2175-2270 9.91e-06

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: 46.77  E-value: 9.91e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  2175 QDAGLLPRCKERRVFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKVSClCLEENVESDPCKFALTSRTGdavETFVLHSS 2254
Cdd:smart00233   10 KSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVRE-APDPDSSKKPHCFEIKTSDR---KTLLLQAE 85

                            90
                    ....*....|....*.
gi 1907111731  2255 SPSVRQTWIHEINQIL 2270
Cdd:smart00233   86 SEEEREKWVEALRKAI 101
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 571-670 1.02e-05

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 46.54  E-value: 1.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  571 FQQDVQQVLDWIENHgEAFLSKhTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIYQAAH 650
Cdd:pfam00435    6 FFRDADDLESWIEEK-EALLSS-EDYGKDLESVQALLKKHKALEAELAAHQDRVEALNELAEKLIDEGHYASEEIQERLE 83

                           90       100
                   ....*....|....*....|
gi 1907111731  651 QLEDRIQDFVRRVEQRKILL 670
Cdd:pfam00435   84 ELNERWEQLLELAAERKQKL 103
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
2803-2874 1.11e-05

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 50.78  E-value: 1.11e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 2803 VAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK----RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:COG0515     12 LRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAAdpeaRERFRREARALARLNHPNIVRVYDVGEEDGRPYLVME 87
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
 2796-2877 1.26e-05

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 49.66  E-value: 1.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2796 FDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD--------QVTH-ELGILQNLQ-HPLLVSLLDTFET 2865
Cdd:cd14093      1 FYAKYEPKEILGRGVSSTVRRCIEKETGQEFAVKIIDITGEKSSeneaeelrEATRrEIEILRQVSgHPNIIELHDVFES 80

                           90
                   ....*....|..
gi 1907111731 2866 PTSYVLVLEILR 2877
Cdd:cd14093     81 PTFIFLVFELCR 92
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 2689-2777 1.32e-05

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 45.92  E-value: 1.32e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKgPEHNTLNNDDHYSISYSDIGEATLKIIGVSTE-DDGIYTCIAVN 2767
Cdd:cd20971      2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWY-RQGKEIIADGLKYRIQEFKGGYHQLIIASVTDdDATVYQVRATN 80

                           90
                   ....*....|
gi 1907111731 2768 DMGSASSSAS 2777
Cdd:cd20971     81 QGGSVSGTAS 90
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 2175-2271 1.54e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.02  E-value: 1.54e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2175 QDAGLLPRCKERRVFLFEQIVIFSepldkKKGFSMPGFLFKNSIKVSCLCLEENVESD----PCKFALTSRTGDAVETFV 2250
Cdd:pfam00169   10 KGGGKKKSWKKRYFVLFDGSLLYY-----KDDKSGKSKEPKGSISLSGCEVVEVVASDspkrKFCFELRTGERTGKRTYL 84

                           90       100
                   ....*....|....*....|.
gi 1907111731 2251 LHSSSPSVRQTWIHEINQILE 2271
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSAIR 105
SH3_Fus1p cd11854
Src homology 3 domain of yeast cell fusion protein Fus1p; Fus1p is required at the cell ...
 1660-1719 1.58e-05

Src homology 3 domain of yeast cell fusion protein Fus1p; Fus1p is required at the cell surface for cell fusion during the mating response in yeast. It requires Bch1p and Bud7p, which are Chs5p-Arf1p binding proteins, for localization to the plasma membrane. It acts as a scaffold protein to assemble a cell surface complex which is involved in septum degradation and inhibition of the NOG pathway to promote cell fusion. The SH3 domain of Fus1p interacts with Bin1p, a formin that controls the assembly of actin cables in response to Cdc42 signaling. It has been shown to bind the motif, R(S/T)(S/T)SL, instead of PxxP motifs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212788 [Multi-domain]  Cd Length: 56  Bit Score: 44.62  E-value: 1.58e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1660 LTVVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVRTTDRSPAAEGLVPCgsLCIA 1719
Cdd:cd11854      1 LMTVISTFEPSLDDELLIKVGETVRVLAEYDD--GWCLVERADGLNGDRGMVPG--ECLQ 56
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
 2805-2876 1.67e-05

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 49.47  E-value: 1.67e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14104      7 ELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFI 78
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 733-1039 1.90e-05

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


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 50.44  E-value: 1.90e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  733 DLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEEL---FQERKIKLElFLQLRIFERDaiDIISDLESWNDEL 809
Cdd:TIGR02168  217 ELKAELRELELALLVLRLEELREELEELQEELKEAEEELEELtaeLQELEEKLE-ELRLEVSELE--EEIEELQKELYAL 293

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  810 SQQMNDFdtedltiaEQRLQHHADKALTMNNLTFDVIHQGQDLLQYVNEVQASGVELLCDRDVDMA--TRVQDLLEFLHE 887
Cdd:TIGR02168  294 ANEISRL--------EQQKQILRERLANLERQLEELEAQLEELESKLDELAEELAELEEKLEELKEelESLEAELEELEA 365

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  888 KQQELDLAAEQHRKHLEQcvqlrhLQAEVKQvlgwIRNGESMLNAGLITASSlqEAEQLQREHEQFQHAIEkTHQSALQV 967
Cdd:TIGR02168  366 ELEELESRLEELEEQLET------LRSKVAQ----LELQIASLNNEIERLEA--RLERLEDRRERLQQEIE-ELLKKLEE 432

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731  968 QQKAEAMLQANHYDMdMIRDCAEKVASHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVLESLEQEYKREED 1039
Cdd:TIGR02168  433 AELKELQAELEELEE-ELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQARLDSLERLQENLEG 503
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
 2806-2875 2.03e-05

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 49.05  E-value: 2.03e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD-----QVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14070     10 LGEGSFAKVREGLHAVTGEKVAIKVIDKKKAKKDsyvtkNLRREGRIQQMIRHPNITQLLDILETENSYYLVMEL 84
IgV_1_Necl_like cd05717
First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the ...
 2696-2775 2.29e-05

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.


Pssm-ID: 409382  Cd Length: 94  Bit Score: 45.20  E-value: 2.29e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2696 SEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDH-------YSISYSDIGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd05717      4 QDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQTIYFNDKralrdsrYQLLNHSASELSISVSNVTLSDEGVYTCLHYTD 83


                   ....*..
gi 1907111731 2769 MGSASSS 2775
Cdd:cd05717     84 PVSTKKV 90
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
 2806-2875 2.54e-05

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 48.56  E-value: 2.54e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNK-KL--MKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14074     11 LGRGHFAVVKLARHVFTGEKVAVKVIDKtKLddVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILEL 83
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
 2806-2874 2.58e-05

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 48.89  E-value: 2.58e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTHELG---ILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05571      3 LGKGTFGKVILCREKATGELYAIKILKKEvIIAKDEVAHTLTenrVLQNTRHPFLTSLKYSFQTNDRLCFVME 75
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 2689-2780 3.26e-05

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 45.24  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2689 PEFVIPLSEVTCETGETVVFRCRVCGRPKASITW-KGPEHNTLNNDDHYS--ISYSDIGEATLKIIG--VSTEDDGIYTC 2763
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWlKNGQPLETDKDDPRShrIVLPSGSLFFLRVVHgrKGRSDEGVYVC 80

                           90
                   ....*....|....*...
gi 1907111731 2764 IAVNDMGSA-SSSASLRV 2780
Cdd:cd07693     81 VAHNSLGEAvSRNASLEV 98
IgV_1_Necl-3 cd07701
First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the ...
 2693-2781 3.29e-05

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region, belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.


Pssm-ID: 409498  Cd Length: 96  Bit Score: 45.08  E-value: 3.29e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2693 IPLSE-VTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDI-------GEATLKIIGVSTEDDGIYTCi 2764
Cdd:cd07701      1 FPLTQnVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIelvraswHELSISISDVSLSDEGQYTC- 79

                           90
                   ....*....|....*..
gi 1907111731 2765 AVNDMGSASSSASLRVL 2781
Cdd:cd07701     80 SLFTMPVKTSKAYLTVL 96
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
 2806-2874 4.24e-05

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 47.70  E-value: 4.24e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQ-HPLLVSLLD-TFETPTSYVLVLE 2874
Cdd:cd13987      1 LGEGTYGKVLLAVHKGSGTKMALKFVPKPSTKLKDFLREYNISLELSvHPHIIKTYDvAFETEDYYVFAQE 71
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 2806-2874 4.54e-05

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 48.28  E-value: 4.54e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:PTZ00263    26 LGTGSFGRVRIAKHKGTGEYYAIKCLKKReILKMKQVQHvaqEKSILMELSHPFIVNMMCSFQDENRVYFLLE 98
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 2151-2275 4.56e-05

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. 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: 270059  Cd Length: 125  Bit Score: 45.23  E-value: 4.56e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2151 LQGFDGKIVAQGKLLLQDTFLVTDQDAGLLP--RCKERRVFLFEQIVIFSEPlDKKKGFSMPGFLFKNSIKVSCLCLEEN 2228
Cdd:cd13239      2 IENYPAPLQALGEPIRQGHFTVWEEAPEVKTssRGHHRHVFLFKNCVVICKP-KRDSRTDTVTYVFKNKMKLSDIDVKDT 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1907111731 2229 VESDPCKFALTSRTGDAVETFVLHSSSPSVRQTWIHEINQIleNQRN 2275
Cdd:cd13239     81 VEGDDRSFGLWHEHRGSVRKYTLQARSAIIKSSWLKDLRDL--QQRL 125
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 2799-2875 4.67e-05

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 47.59  E-value: 4.67e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 2799 FYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14108      3 YYDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTEL 79
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
 2800-2874 5.48e-05

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 47.38  E-value: 5.48e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKK-----LMKRDQ----VTHELGILQNLQ---HPLLVSLLDTFETPT 2867
Cdd:cd14004      2 YTILKEMGEGAYGQVNLAIYKSKGKEVVIKFIFKErilvdTWVRDRklgtVPLEIHILDTLNkrsHPNIVKLLDFFEDDE 81


                   ....*..
gi 1907111731 2868 SYVLVLE 2874
Cdd:cd14004     82 FYYLVME 88
Ig3_L1-CAM cd05876
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here ...
 2703-2780 6.03e-05

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409460 [Multi-domain]  Cd Length: 83  Bit Score: 43.75  E-value: 6.03e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2703 GETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISysdigEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd05876     10 GQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNH-----NKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82
IgI_7_Dscam cd20954
Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar ...
 2688-2774 6.80e-05

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409546 [Multi-domain]  Cd Length: 96  Bit Score: 43.84  E-value: 6.80e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITWK---GP---EHNTLNNDDHYSIsysdIGEATLKIIGVSTEDDGIY 2761
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKkatGStpgEYKDLLYDPNVRI----LPNGTLVFGHVQKENEGHY 76

                           90
                   ....*....|...
gi 1907111731 2762 TCIAVNDMGSASS 2774
Cdd:cd20954     77 LCEAKNGIGSGLS 89
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
 2800-2874 6.97e-05

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 47.33  E-value: 6.97e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD---QVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14069      3 WDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPGDcpeNIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLE 80
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
 2805-2874 9.48e-05

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 46.90  E-value: 9.48e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKlmKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14010      7 EIGRGKHSVVYKGRRKGTIEFVAIKCVDKS--KRPEVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVE 74
IgI_Titin_M1-like cd20927
Immunoglobulin-like M1 domain from Titin; a member of the I-set of IgSF domains; The members ...
 2701-2780 9.68e-05

Immunoglobulin-like M1 domain from Titin; a member of the I-set of IgSF domains; The members here are composed of the Immunoglobulin-like M1 I-set domain from Titin and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin-M1 domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409521  Cd Length: 90  Bit Score: 43.49  E-value: 9.68e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2701 ETGETVVFRCRVCGRPKAS-ITWKGPEHNtLNNDDHYSISYSDiGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLR 2779
Cdd:cd20927     12 EEGGHVKYVCKIENYDQSTqVTWYFGVRQ-LENSEKYEITYED-GVAILYVKDITKFDDGTYRCKVVNDYGEDSSYAELF 89


                   .
gi 1907111731 2780 V 2780
Cdd:cd20927     90 V 90
Ig_DSCAM cd05734
Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members ...
 2688-2780 1.15e-04

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.


Pssm-ID: 409397 [Multi-domain]  Cd Length: 97  Bit Score: 43.25  E-value: 1.15e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITW---KGPEHNTlnnddHYSISYSD-----IGEATLKIIGVSTEDDG 2759
Cdd:cd05734      1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkhsKGSGVPQ-----FQHIVPLNgriqlLSNGSLLIKHVLEEDSG 75

                           90       100
                   ....*....|....*....|..
gi 1907111731 2760 IYTCIAVNDMGS-ASSSASLRV 2780
Cdd:cd05734     76 YYLCKVSNDVGAdISKSMYLTV 97
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
 2798-2874 1.15e-04

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 46.56  E-value: 1.15e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2798 AFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKlmKRDQVTH-----ELGILQNLQHPLLVSLLDTFETPTSYVLV 2872
Cdd:cd14075      2 GFYRIRGELGSGNFSQVKLGIHQLTKEKVAIKILDKT--KLDQKTQrllsrEISSMEKLHHPNIIRLYEVVETLSKLHLV 79


                   ..
gi 1907111731 2873 LE 2874
Cdd:cd14075     80 ME 81
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
 2156-2272 1.16e-04

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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: 270134  Cd Length: 114  Bit Score: 43.88  E-value: 1.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2156 GKIVAQGKLLLQDTFLVTDQDAgllpRCKERRVFLFEQIVIFSepldKKKGFSMPG--FLFKNSIKVScLCLEENVESDP 2233
Cdd:cd13325      1 GNIHKLGRLLRHDWFTVTDGEG----KAKERYLFLFKSRILIT----KVRRISEDRsvFILKDIIRLP-EVNVKQHPDDE 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1907111731 2234 CKFAL---TSRTGDAVETFVLHSssPSVRQTWIHEINQILEN 2272
Cdd:cd13325     72 RTFELqpkLPAFGILPIDFKAHK--DEIKDYWLNEIEEYAND 111
MukB COG3096
Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell ...
 574-914 1.22e-04

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 442330 [Multi-domain]  Cd Length: 1470  Bit Score: 48.02  E-value: 1.22e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  574 DVQQVLDwienhgeaflSKHTgvgkslhraRALQkrhedfeevaqntYTNADKLLEAAEQLAQTGECDPEEI--YQAAHQ 651
Cdd:COG3096    400 DYQQALD----------VQQT---------RAIQ-------------YQQAVQALEKARALCGLPDLTPENAedYLAAFR 447

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  652 L-EDRIQDFVRRVEQRKILLDMSVSFHTHVKELwtwleeLQKeLLDDVYAESV-EAVQDLIKRFgqqqqttlQVTVNVIK 729
Cdd:COG3096    448 AkEQQATEEVLELEQKLSVADAARRQFEKAYEL------VCK-IAGEVERSQAwQTARELLRRY--------RSQQALAQ 512

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  730 EGEDLIQQLRDsaissnktphnssinhIETVLQQLDEAQSQMEELFQERKIKLELFLQLRiferdaiDIISDLESWNDEL 809
Cdd:COG3096    513 RLQQLRAQLAE----------------LEQRLRQQQNAERLLEEFCQRIGQQLDAAEELE-------ELLAELEAQLEEL 569

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  810 SQQMNDFdTEDLTIAEQRLQHHADKaltMNNLTFD--VIHQGQDLLQYVNEvqASGVELLCDRDVdMATRvQDLLEFLHE 887
Cdd:COG3096    570 EEQAAEA-VEQRSELRQQLEQLRAR---IKELAARapAWLAAQDALERLRE--QSGEALADSQEV-TAAM-QQLLERERE 641

                          330       340
                   ....*....|....*....|....*..
gi 1907111731  888 KQQELDLAAEQhRKHLEQcvQLRHLQA 914
Cdd:COG3096    642 ATVERDELAAR-KQALES--QIERLSQ 665
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 2703-2780 1.30e-04

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 42.97  E-value: 1.30e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2703 GETVVFRCRVCGRPKASITW-KGPEhnTLNNDDHYSISysdigEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd05728     14 GSSLRWECKASGNPRPAYRWlKNGQ--PLASENRIEVE-----AGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
 2701-2780 1.54e-04

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 43.02  E-value: 1.54e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2701 ETGETVVFRCRVCGRPKASITW-KGPEHNTLNNDDHYSIsysdIGEAT-LKIIGVSTEDDGIYTCIAVNDMGSASSSASL 2778
Cdd:cd05736     13 EPGVEASLRCHAEGIPLPRVQWlKNGMDINPKLSKQLTL----IANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSL 88


                   ..
gi 1907111731 2779 RV 2780
Cdd:cd05736     89 FV 90
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 2692-2781 1.63e-04

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 42.99  E-value: 1.63e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2692 VIPLsEVTCETGETVVFRCRVCGRPKASITWK---GPEHNTLNNDDHYSISYSDIgeatLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd05763      4 KTPH-DITIRAGSTARLECAATGHPTPQIAWQkdgGTDFPAARERRMHVMPEDDV----FFIVDVKIEDTGVYSCTAQNS 78

                           90
                   ....*....|...
gi 1907111731 2769 MGSASSSASLRVL 2781
Cdd:cd05763     79 AGSISANATLTVL 91
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 766-977 1.76e-04

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


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 47.24  E-value: 1.76e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  766 EAQSQMEELfQERKIKLeLFLQLRIFERDAIDIISDLESWNDELSQQMNDFDTEDLTIAEQRLQHHAdkaltmnnLTFDV 845
Cdd:COG1196    214 RYRELKEEL-KELEAEL-LLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEE--------LELEL 283

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  846 IHQGQDLLQYVNEVQA--SGVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQVLgwI 923
Cdd:COG1196    284 EEAQAEEYELLAELARleQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAEL--A 361

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907111731  924 RNGESMLNAGLITASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQA 977
Cdd:COG1196    362 EAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLER 415
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
 2806-2874 1.79e-04

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 45.84  E-value: 1.79e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQ----VTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14073      9 LGKGTYGKVKLAIERATGREVAIKSIKKDKIEDEQdmvrIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVME 81
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 2694-2774 1.85e-04

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 42.61  E-value: 1.85e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITW-KGPEHNTLNNddhySISYSDIGeaTLKIIGVSTEDDGIYTCIAVNDMGSA 2772
Cdd:cd20968      5 PPTNVTIIEGLKAVLPCTTMGNPKPSVSWiKGDDLIKENN----RIAVLESG--SLRIHNVQKEDAGQYRCVAKNSLGIA 78


                   ..
gi 1907111731 2773 SS 2774
Cdd:cd20968     79 YS 80
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
 2796-2877 1.91e-04

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 46.55  E-value: 1.91e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2796 FDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKlmKRDQvTHELGILQNL-QHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14176     17 FTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKS--KRDP-TEEIEILLRYgQHPNIITLKDVYDDGKYVYVVTE 93


                   ...
gi 1907111731 2875 ILR 2877
Cdd:cd14176     94 LMK 96
sbcc TIGR00618
exonuclease SbcC; All proteins in this family for which functions are known are part of an ...
 417-973 1.99e-04

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129705 [Multi-domain]  Cd Length: 1042  Bit Score: 47.27  E-value: 1.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  417 QQIKQIANQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKYMSNVDSWCKACGEVDLPSELQDLEDAIHHHQGIYEHITl 496
Cdd:TIGR00618  314 TELQSKMRSRAKLLMKRAAHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLT- 392

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  497 aysEVSQDGKSLLDKLQRplTPGSSDSLTASAN---YSKAVHHVLDVIHEVLHHQRQL--ENIWQHRK------VRLHQR 565
Cdd:TIGR00618  393 ---QKLQSLCKELDILQR--EQATIDTRTSAFRdlqGQLAHAKKQQELQQRYAELCAAaiTCTAQCEKlekihlQESAQS 467

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  566 LQLCVFQ-QDVQQVLDWIENHG---EAFLSKHTGV-----GKSLHRARALQKRHE---DFEEVAQNTYTNAdKLLEAAEQ 633
Cdd:TIGR00618  468 LKEREQQlQTKEQIHLQETRKKavvLARLLELQEEpcplcGSCIHPNPARQDIDNpgpLTRRMQRGEQTYA-QLETSEED 546

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  634 LAQTGECDPEEIYQAAHQLEDRIQDFVRRVEQRKILLDMSVSFHTHVKELWTWLE---ELQKELLDDVYAESVE-----A 705
Cdd:TIGR00618  547 VYHQLTSERKQRASLKEQMQEIQQSFSILTQCDNRSKEDIPNLQNITVRLQDLTEklsEAEDMLACEQHALLRKlqpeqD 626

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  706 VQDLIKRFGQQQQTTLQVTVNVIKEGEDLIQQ-LRDSAISSNKTPHNSsinhIETVLQQLDEAQSQMEELFQERKIKLEL 784
Cdd:TIGR00618  627 LQDVRLHLQQCSQELALKLTALHALQLTLTQErVREHALSIRVLPKEL----LASRQLALQKMQSEKEQLTYWKEMLAQC 702

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  785 FLQLRIFERDAIDIISDLESWNDELSQQMNDFDTEDLTIAE--QRLQHHADKALtmnnltfdvihQGQDLLQYVNEVQAS 862
Cdd:TIGR00618  703 QTLLRELETHIEEYDREFNEIENASSSLGSDLAAREDALNQslKELMHQARTVL-----------KARTEAHFNNNEEVT 771

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  863 GVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQvlgwiRNGESMLNAGLITASSLQE 942
Cdd:TIGR00618  772 AALQTGAELSHLAAEIQFFNRLREEDTHLLKTLEAEIGQEIPSDEDILNLQCETLV-----QEEEQFLSRLEEKSATLGE 846

                          570       580       590
                   ....*....|....*....|....*....|..
gi 1907111731  943 AEQLQREHEQ-FQHAIEKTHQSALQVQQKAEA 973
Cdd:TIGR00618  847 ITHQLLKYEEcSKQLAQLTQEQAKIIQLSDKL 878
Ig2_PTK7 cd05760
Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here ...
 2694-2775 2.12e-04

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.


Pssm-ID: 409417  Cd Length: 95  Bit Score: 42.61  E-value: 2.12e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2694 PLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSdigEATLKIIGVSTEDDGIYTCIAVNDMGSAS 2773
Cdd:cd05760      7 PASAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSK---ERTLTLRSAGPDDSGLYYCCAHNAFGSVC 83


                   ..
gi 1907111731 2774 SS 2775
Cdd:cd05760     84 SS 85
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
 2799-2874 2.18e-04

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 45.46  E-value: 2.18e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2799 FYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD---QVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14071      1 FYDIERTIGKGNFAVVKLARHRITKTEVAIKIIDKSQLDEEnlkKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTE 79
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
 2800-2874 2.46e-04

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 45.77  E-value: 2.46e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVA---------TKFVNKKLMKrdqvthELGILQNLQHPLLVSLLDTFETPTSYV 2870
Cdd:cd07833      3 YEVLGVVGEGAYGVVLKCRNKATGEIVAikkfkesedDEDVKKTALR------EVKVLRQLRHENIVNLKEAFRRKGRLY 76


                   ....
gi 1907111731 2871 LVLE 2874
Cdd:cd07833     77 LVFE 80
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
 2806-2874 2.63e-04

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 45.77  E-value: 2.63e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTH---ELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05595      3 LGKGTFGKVILVREKATGRYYAMKILRKEvIIAKDEVAHtvtESRVLQNTRHPFLTALKYAFQTHDRLCFVME 75
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
 2806-2876 2.70e-04

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 45.60  E-value: 2.70e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQ----VTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd05577      1 LGRGGFGEVCACQVKATGKMYACKKLDKKRIKKKKgetmALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLM 75
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
 1666-1698 2.96e-04

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


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 40.82  E-value: 2.96e-04
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1907111731 1666 DFTACNSNELTIRRGQTVEVLErPHDK---PDWCLV 1698
Cdd:cd11800      7 TFEARSPGELSVTEGQVVTVLE-KHDLkgnPEWWLV 41
Ig_Perlecan_like cd05743
Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan ...
 2703-2770 3.22e-04

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.


Pssm-ID: 143220  Cd Length: 78  Bit Score: 41.71  E-value: 3.22e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2703 GETVVFRCRVCGRPKASITWKgpehntLN----NDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMG 2770
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWR------LNwghvPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRG 66
IgI_3_FGFR cd04974
Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of ...
 2699-2778 3.43e-04

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409363  Cd Length: 102  Bit Score: 42.41  E-value: 3.43e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2699 TCETGETVVFRCRVCGRPKASITWKgpEHNTLNNDDHYSISY--------SDIG----EATLKIIGVSTEDDGIYTCIAV 2766
Cdd:cd04974     12 TVVLGSDVEFHCKVYSDAQPHIQWL--KHVEVNGSKYGPDGLpyvtvlkvAGVNttgeENTLTISNVTFDDAGEYICLAG 89

                           90
                   ....*....|..
gi 1907111731 2767 NDMGSASSSASL 2778
Cdd:cd04974     90 NSIGLSFHSAWL 101
IgV_HHLA2 cd16091
Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are ...
 2696-2780 3.44e-04

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.


Pssm-ID: 409512  Cd Length: 107  Bit Score: 42.37  E-value: 3.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2696 SEVTCETGETVVFRCRVCGRPKASITWKGPE-----HNTLNNDDHY-----------SISYSDI--GEATLKIIGVSTED 2757
Cdd:cd16091      5 VIVVCLLSEDCILPCSFTPGSEVVIHWYKQDsdikvHSYYYGKDQLesqdqryrnrtSLFKDQIsnGNASLLLRRVQLQD 84

                           90       100
                   ....*....|....*....|...
gi 1907111731 2758 DGIYTCIAVNDMGSASSSASLRV 2780
Cdd:cd16091     85 EGRYKCYTSTIIGNQESFVNLKV 107
IgI_NCAM-1_like cd05732
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar ...
 2692-2780 3.71e-04

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 409395 [Multi-domain]  Cd Length: 96  Bit Score: 42.13  E-value: 3.71e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2692 VIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNND---DHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVND 2768
Cdd:cd05732      5 ITYLENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEgdlDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEASNR 84

                           90
                   ....*....|..
gi 1907111731 2769 MGSASSSASLRV 2780
Cdd:cd05732     85 IGGDQQSMYLEV 96
SH3_Bzz1_1 cd11912
First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
 1663-1712 3.72e-04

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


Pssm-ID: 212845 [Multi-domain]  Cd Length: 55  Bit Score: 40.67  E-value: 3.72e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1663 VIHDFTACNSNELTIRRGQTVEVLErPHDKPDWCLVRTTDrspAAEGLVP 1712
Cdd:cd11912      4 VLYDYTASGDDEVSISEGEEVTVLE-PDDGSGWTKVRNGS---GEEGLVP 49
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
 1659-1712 3.96e-04

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


Pssm-ID: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 40.76  E-value: 3.96e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 1659 ELTVVIHDFTACNSNELTIRRGQTVEVLERPHDKpDWCLVRttDRSPAAEGLVP 1712
Cdd:cd11775      1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKKSK-DWWMVE--NVSTGKEGVVP 51
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
 2806-2874 4.12e-04

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 45.39  E-value: 4.12e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTHELG----ILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05575      3 IGKGSFGKVLLARHKAEGKLYAVKVLQKKaILKRNEVKHIMAernvLLKNVKHPFLVGLHYSFQTKDKLYFVLD 76
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 2803-2859 4.28e-04

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 44.75  E-value: 4.28e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 2803 VAELGRGRFAVVKKCDQKGtKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSL 2859
Cdd:cd05059      9 LKELGSGQFGVVHLGKWRG-KIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQL 64
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
 1664-1712 4.67e-04

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


Pssm-ID: 212837 [Multi-domain]  Cd Length: 57  Bit Score: 40.40  E-value: 4.67e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1907111731 1664 IHDFTACNSNELTIRRGQTVEVLERPHDKPDWCLVRTTDrspAAEGLVP 1712
Cdd:cd11904      6 LYPFSSSNDEELNFEKGEVMDVIEKPENDPEWWKCRKAN---GQVGLVP 51
IgI_3_Contactin-1 cd05851
Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) ...
 2688-2780 5.30e-04

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 143259  Cd Length: 88  Bit Score: 41.16  E-value: 5.30e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2688 PPEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKgpehnTLNNDDHYSISYSDIGeATLKIIGVSTEDDGIYTCIAVN 2767
Cdd:cd05851      1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWR-----KILEPMPATAEISMSG-AVLKIFNIQPEDEGTYECEAEN 74

                           90
                   ....*....|...
gi 1907111731 2768 DMGSASSSASLRV 2780
Cdd:cd05851     75 IKGKDKHQARVYV 87
SH3_ARHGEF37_C2 cd11941
Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 ...
 1662-1718 5.48e-04

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212874  Cd Length: 57  Bit Score: 40.28  E-value: 5.48e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLErPHDK---PDWCLVRTTDRspaaEGLVPCGSLCI 1718
Cdd:cd11941      3 VAAYPFTARSKHEVSLQAGQPVTVLE-PHDKkgsPEWSLVEVNGQ----RGYVPSSYLAR 57
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
 2800-2875 5.66e-04

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 44.47  E-value: 5.66e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK----RDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14099      3 YRRGKFLGKGGFAKCYEVTDMSTGKVYAGKVVPKSSLTkpkqREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLEL 82
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 220-338 5.83e-04

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 41.54  E-value: 5.83e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  220 FEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKK--KVIKAPIEDLDLEGQKLLQRiQSSDSfpkkns 297
Cdd:pfam00435    3 LQQFFRDADDLESWIEEKEALLSSEDYGKDLESVQALLKKHKALEAelAAHQDRVEALNELAEKLIDE-GHYAS------ 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907111731  298 gsgnadlqnllPKVSTMLDRLHSTRQHLHQMWHVRKLKLDQ 338
Cdd:pfam00435   76 -----------EEIQERLEELNERWEQLLELAAERKQKLEE 105
SH3_Nck2_3 cd11903
Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
 1664-1712 7.15e-04

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


Pssm-ID: 212836 [Multi-domain]  Cd Length: 59  Bit Score: 40.04  E-value: 7.15e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1907111731 1664 IHDFTACNSNELTIRRGQTVEVLERPHDKPDWCLVRTtdrSPAAEGLVP 1712
Cdd:cd11903      6 LYPFSSVTEEELNFEKGETMEVIEKPENDPEWWKCKN---SRGQVGLVP 51
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
 2800-2874 7.20e-04

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 43.91  E-value: 7.20e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907111731 2800 YSEVAE-LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRD--QVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14078      4 YYELHEtIGSGGFAKVKLATHILTGEKVAIKIMDKKALGDDlpRVKTEIEALKNLSHQHICRLYHVIETDNKIFMVLE 81
IgI_3_Contactin cd04968
Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) ...
 2697-2770 7.37e-04

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409357 [Multi-domain]  Cd Length: 88  Bit Score: 40.99  E-value: 7.37e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 2697 EVTCETGETVVFRCRVCGRPKASITWK---GPEHNTlnnddhYSISYSdigEATLKIIGVSTEDDGIYTCIAVNDMG 2770
Cdd:cd04968     10 DTYALKGQTVTLECFALGNPVPQIKWRkvdGSPSSQ------WEITTS---EPVLEIPNVQFEDEGTYECEAENSRG 77
IgV_1_Necl-1 cd05882
First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member ...
 2696-2763 7.57e-04

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons.


Pssm-ID: 143290  Cd Length: 95  Bit Score: 41.19  E-value: 7.57e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2696 SEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLN-------NDDHYSISYSDIGEATLKIIGVSTEDDGIYTC 2763
Cdd:cd05882      5 QDETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYfgekralRDNRIQLVKSTPTELIISISNVQLSDEGEYTC 79
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
 2805-2877 8.00e-04

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 44.23  E-value: 8.00e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKlmKRDQvTHELGILQNL-QHPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14178     10 DIGIGSYSVCKRCVHKATSTEYAVKIIDKS--KRDP-SEEIEILLRYgQHPNIITLKDVYDDGKFVYLVMELMR 80
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 2710-2778 8.73e-04

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 40.24  E-value: 8.73e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2710 CRVCGRPKASITWKgPEHNTLNNDDHYSISysdiGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASL 2778
Cdd:cd05746      5 CSAQGDPEPTITWN-KDGVQVTESGKFHIS----PEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 2800-2874 8.91e-04

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 43.99  E-value: 8.91e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14662      2 YELVKDIGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVME 76
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
 2806-2875 9.34e-04

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 43.70  E-value: 9.34e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKR----DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14186      9 LGKGSFACVYRARSLHTGLEVAIKMIDKKAMQKagmvQRVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEM 82
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 544-846 1.03e-03

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


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 45.05  E-value: 1.03e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  544 VLHHQRQLENIWQHRKVRLHQRLQLCVFQQDVQQVLDWIENHGEAFLSKHTGVGKSLHRARALQKRHEDFEEVAQNTYTN 623
Cdd:TIGR02168  672 ILERRREIEELEEKIEELEEKIAELEKALAELRKELEELEEELEQLRKELEELSRQISALRKDLARLEAEVEQLEERIAQ 751

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  624 ADKLLEAAEQLAQTGECDPEEIYQAAHQLEDRIQDFVRRVEQRKILLdmsvsfhthvKELWTWLEELQKEL--LDDVYAE 701
Cdd:TIGR02168  752 LSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEEL----------KALREALDELRAELtlLNEEAAN 821

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  702 SVEAVQDLIKRfgqqqqttlqvTVNVIKEGEDLIQQLRDSAissnktphnssiNHIETVLQQLDEAQSQMEELFQERKIK 781
Cdd:TIGR02168  822 LRERLESLERR-----------IAATERRLEDLEEQIEELS------------EDIESLAAEIEELEELIEELESELEAL 878

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731  782 LELF----LQLRIFERDAIDIISDLESWN----------DELSQQMNDFDTEdLTIAEQRLQHHADKALTMNNLTFDVI 846
Cdd:TIGR02168  879 LNERasleEALALLRSELEELSEELRELEskrselrrelEELREKLAQLELR-LEGLEVRIDNLQERLSEEYSLTLEEA 956
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
 1662-1712 1.06e-03

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212787  Cd Length: 59  Bit Score: 39.35  E-value: 1.06e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERphDKPDWCLVR--TTDRSPAAEGLVP 1712
Cdd:cd11853      3 PVIQDYYALKEDEICVSQGEVVQILAA--NQQNMFLVYrpATDQSPAAEGWIP 53
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
 2806-2874 1.09e-03

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 43.46  E-value: 1.09e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKR-AVATKFVNKKLMKRDQ--VTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14202     10 IGHGAFAVVFKGRHKEKHDlEVAVKCINKKNLAKSQtlLGKEIKILKELKHENIVALYDFQEIANSVYLVME 81
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
 1662-1713 1.09e-03

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


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 39.26  E-value: 1.09e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkPDWCLVRTTDRspaaEGLVPC 1713
Cdd:cd11804      3 VAKHDFKATAEDELSFKKGSILKVLNMEDD-PNWYKAELDGK----EGLIPK 49
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 2690-2782 1.32e-03

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 40.32  E-value: 1.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2690 EFVIPLSEVTCETGETVVFRCRVCGRPKASITWK--GPEHNTLNNDDHYS---ISYSDIGEatLKIIGVSTEDDGIYTCI 2764
Cdd:cd05726      1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQkeGSQNLLFPYQPPQPssrFSVSPTGD--LTITNVQRSDVGYYICQ 78

                           90
                   ....*....|....*...
gi 1907111731 2765 AVNDMGSASSSASLRVLG 2782
Cdd:cd05726     79 ALNVAGSILAKAQLEVTD 96
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
 1660-1712 1.35e-03

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212784  Cd Length: 56  Bit Score: 38.93  E-value: 1.35e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 1660 LTVVIHDFTACNSNELTIRRGQTVEVLERPHDKpDWCLVRTtdRSPAAEGLVP 1712
Cdd:cd11850      1 LFVALYDFVASGENQLSIKKGEQLRVLGYNKNG-EWCEAES--KSTGGQGWVP 50
Spectrin pfam00435
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ...
 676-783 1.41e-03

Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated.


Pssm-ID: 395348 [Multi-domain]  Cd Length: 105  Bit Score: 40.38  E-value: 1.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  676 FHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKRFGQQQQTTLQVTVNViKEGEDLIQQLRDSAISSNKtphnssin 755
Cdd:pfam00435    6 FFRDADDLESWIEEKEALLSSEDYGKDLESVQALLKKHKALEAELAAHQDRV-EALNELAEKLIDEGHYASE-------- 76

                           90       100
                   ....*....|....*....|....*...
gi 1907111731  756 HIETVLQQLDEAQSQMEELFQERKIKLE 783
Cdd:pfam00435   77 EIQERLEELNERWEQLLELAAERKQKLE 104
CwlO1 COG3883
Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function ...
 740-977 1.50e-03

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];


Pssm-ID: 443091 [Multi-domain]  Cd Length: 379  Bit Score: 43.67  E-value: 1.50e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  740 DSAISSNKTPHNSSINHIETVLQQLDEAQSQMEELFQErkiklelflqlriferdaidiISDLESWNDELSQQMNDFdTE 819
Cdd:COG3883     15 DPQIQAKQKELSELQAELEAAQAELDALQAELEELNEE---------------------YNELQAELEALQAEIDKL-QA 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  820 DLTIAEQRLQHHADK------ALTMNNLT---FDVIHQGQDLLQYVNEVQAsgVELLCDRDVDMATRVQDLLEFLHEKQQ 890
Cdd:COG3883     73 EIAEAEAEIEERREElgerarALYRSGGSvsyLDVLLGSESFSDFLDRLSA--LSKIADADADLLEELKADKAELEAKKA 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  891 ELDLA-AEQHRKHLEQCVQLRHLQAEVKQVLGWIRNgesmLNAGLitASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQ 969
Cdd:COG3883    151 ELEAKlAELEALKAELEAAKAELEAQQAEQEALLAQ----LSAEE--AAAEAQLAELEAELAAAEAAAAAAAAAAAAAAA 224


                   ....*...
gi 1907111731  970 KAEAMLQA 977
Cdd:COG3883    225 AAAAAAAA 232
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 2806-2877 1.51e-03

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 43.49  E-value: 1.51e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQvtHELGILQNLQ-HPLLVSLLDTFETPTSYVLVLEILR 2877
Cdd:cd14179     15 LGEGSFSICRKCLHKKTNQEYAVKIVSKRMEANTQ--REIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLK 85
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
 1662-1718 1.58e-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: 38.89  E-value: 1.58e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907111731 1662 VVIHDFTACNSNELTIRRGQTVEVLERPHDkpDWCLVrttDRSpAAEGLVPCGSLCI 1718
Cdd:cd11824      3 SVLYDYTAQEDDELSISKGDVVAVIEKGED--GWWTV---ERN-GQKGLVPGTYLEK 53
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 2702-2781 1.73e-03

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 39.74  E-value: 1.73e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2702 TGETVVFRCRVCGRPKASITW---KGPEH----NTLNNDDHYSISYSDigeatlkiigVSTEDDGIYTCIAVNDMGSASS 2774
Cdd:cd04978     13 PGETGELICEAEGNPQPTITWrlnGVPIEpapeDMRRTVDGRTLIFSN----------LQPNDTAVYQCNASNVHGYLLA 82


                   ....*..
gi 1907111731 2775 SASLRVL 2781
Cdd:cd04978     83 NAFLHVL 89
Ig6_Contactin cd04970
Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth ...
 2701-2783 1.74e-03

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409359  Cd Length: 102  Bit Score: 40.23  E-value: 1.74e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2701 ETGETVVFRCRVCGRPKASIT--WkgpEHNTLNND-----DHYSISY--SDIGEatLKIIGVSTEDDGIYTCIAVNDMGS 2771
Cdd:cd04970     15 TVGENATLQCHASHDPTLDLTftW---SFNGVPIDlekieGHYRRRYgkDSNGD--LEIVNAQLKHAGRYTCTAQTVVDS 89

                           90
                   ....*....|..
gi 1907111731 2772 ASSSASLRVLGP 2783
Cdd:cd04970     90 DSASATLVVRGP 101
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 2692-2775 1.87e-03

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 39.30  E-value: 1.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2692 VIPLSEVTCETGETVVFRCRVCGRPKASITWKGPehNTLNNDDHYSISYSdigeatlkiigVSTEDDGIYTCIAVNDMGS 2771
Cdd:pfam13895    3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKD--GSAISSSPNFFTLS-----------VSAEDSGTYTCVARNGRGG 69


                   ....
gi 1907111731 2772 ASSS 2775
Cdd:pfam13895   70 KVSN 73
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
 2806-2877 2.02e-03

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 43.04  E-value: 2.02e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMK---------RDQVTHELGILQNLQ-HPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14181     18 IGRGVSSVVRRCVHRHTGQEFAVKIIEVTAERlspeqleevRSSTLKEIHILRQVSgHPSIITLIDSYESSTFIFLVFDL 97


                   ..
gi 1907111731 2876 LR 2877
Cdd:cd14181     98 MR 99
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
 1660-1712 2.07e-03

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


Pssm-ID: 212798  Cd Length: 58  Bit Score: 38.77  E-value: 2.07e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907111731 1660 LTVVIHDFTACNSNELTIRRGQTVEVLER---PHdKPDWCLVRTTDRSPaaeGLVP 1712
Cdd:cd11864      1 VARAEYDFVAESEDELSFRAGDKLRLAPKelqPR-VRGWLLATVDGQKI---GLVP 52
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 2698-2780 2.10e-03

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 39.50  E-value: 2.10e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2698 VTCETGETVVFRCRVCGRPKASITWKGPEHNtLNNDDHYSISYSDIgEATLKIIGVSTEDDGIYTCIAVNDMGSASSSAS 2777
Cdd:cd05748      2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQP-LKETGRVQIETTAS-STSLVIKNAKRSDSGKYTLTLKNSAGEKSATIN 79


                   ...
gi 1907111731 2778 LRV 2780
Cdd:cd05748     80 VKV 82
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
 2806-2874 2.26e-03

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 43.09  E-value: 2.26e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTHELG---ILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05594     33 LGKGTFGKVILVKEKATGRYYAMKILKKEvIVAKDEVAHTLTenrVLQNSRHPFLTALKYSFQTHDRLCFVME 105
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
 2806-2874 2.42e-03

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 42.24  E-value: 2.42e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNK-KLMKRDQ---VTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14081      9 LGKGQTGLVKLAKHCVTGQKVAIKIVNKeKLSKESVlmkVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVLE 81
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
 2806-2876 2.59e-03

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 42.56  E-value: 2.59e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQ----VTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd05608      9 LGKGGFGEVSACQMRATGKLYACKKLNKKRLKKRKgyegAMVEKRILAKVHSRFIVSLAYAFQTKTDLCLVMTIM 83
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 2806-2876 2.82e-03

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 42.39  E-value: 2.82e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKR----DQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEIL 2876
Cdd:cd14663      8 LGEGTFAKVKFARNTKTGESVAIKIIDKEQVARegmvEQIKREIAIMKLLRHPNIVELHEVMATKTKIFFVMELV 82
IgI_3_FGFR2 cd05858
Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member ...
 2696-2781 2.93e-03

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409444  Cd Length: 105  Bit Score: 39.56  E-value: 2.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2696 SEVTCETGETVVFRCRVCGRPKASITWKgpehntlnndDHYSISYSDIGE------ATLKIIGVST-------------- 2755
Cdd:cd05858      9 ANTSVVVGTDAEFVCKVYSDAQPHIQWL----------KHVEKNGSKYGPdglpyvEVLKTAGVNTtdkeievlylrnvt 78

                           90       100
                   ....*....|....*....|....*..
gi 1907111731 2756 -EDDGIYTCIAVNDMGSASSSASLRVL 2781
Cdd:cd05858     79 fEDAGEYTCLAGNSIGISHHSAWLTVL 105
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
 2800-2875 3.14e-03

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 42.15  E-value: 3.14e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKK---LMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEI 2875
Cdd:cd14097      3 YTFGRKLGQGSFGVVIEATHKETQTKWAIKKINREkagSSAVKLLEREVDILKHVNHAHIIHLEEVFETPKRMYLVMEL 81
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
 2805-2874 3.57e-03

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 41.87  E-value: 3.57e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907111731 2805 ELGRGRFAVVKKCDQKGTKRAVATKFVNKKLM----KRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd08224      7 KIGKGQFSVVYRARCLLDGRLVALKKVQIFEMmdakARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLE 80
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 209-339 3.96e-03

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 41.28  E-value: 3.96e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731  209 NHEEWIEIRVAFEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKKKV--IKAPIEDLDLEGQKLLQRI 286
Cdd:cd00176     97 ERRQRLEEALDLQQFFRDADDLEQWLEEKEAALASEDLGKDLESVEELLKKHKELEEELeaHEPRLKSLNELAEELLEEG 176

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907111731  287 QSSDsfpkknsgsgnadlqnlLPKVSTMLDRLHSTRQHLHQMWHVRKLKLDQC 339
Cdd:cd00176    177 HPDA-----------------DEEIEEKLEELNERWEELLELAEERQKKLEEA 212
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 2800-2874 4.08e-03

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 41.89  E-value: 4.08e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907111731 2800 YSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14665      2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVME 76
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 2184-2266 4.42e-03

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: 38.68  E-value: 4.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2184 KERRVFLFEQIVIFSEplDKKKGFSMPgflfKNSIKVS--CLCLEENVESDPCKFALTSRTGdavETFVLHSSSPSVRQT 2261
Cdd:cd00821     17 KKRWFVLFEGVLLYYK--SKKDSSYKP----KGSIPLSgiLEVEEVSPKERPHCFELVTPDG---RTYYLQADSEEERQE 87


                   ....*
gi 1907111731 2262 WIHEI 2266
Cdd:cd00821     88 WLKAL 92
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
 2806-2874 6.32e-03

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 41.61  E-value: 6.32e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVNKK-LMKRDQVTHELG---ILQNLQHPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd05593     23 LGKGTFGKVILVREKASGKYYAMKILKKEvIIAKDEVAHTLTesrVLKNTRHPFLTSLKYSFQTKDRLCFVME 95
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
 1667-1712 7.37e-03

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


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 36.91  E-value: 7.37e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1907111731 1667 FTACNSNELTIRRGQTVEVLERPHDKPDWCLVRttdRSPAAEGLVP 1712
Cdd:cd11767      8 FTGENDEELSFEKGERLEIIEKPEDDPDWWKAR---NALGTTGLVP 50
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 2800-2874 8.64e-03

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 40.68  E-value: 8.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2800 YSEVAELGRGRFAVV----KKCDQkgtkRAVATKFVNKKLMKR-------DQVTHELGIL---QNLQHPLLVSLLDTFET 2865
Cdd:cd14005      2 YEVGDLLGKGGFGTVysgvRIRDG----LPVAVKFVPKSRVTEwamingpVPVPLEIALLlkaSKPGVPGVIRLLDWYER 77


                   ....*....
gi 1907111731 2866 PTSYVLVLE 2874
Cdd:cd14005     78 PDGFLLIME 86
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
 2806-2877 9.84e-03

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 40.67  E-value: 9.84e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907111731 2806 LGRGRFAVVKKCDQKGTKRAVATKFVN---KKLMKRDQVTH-------ELGILQNLQ-HPLLVSLLDTFETPTSYVLVLE 2874
Cdd:cd14182     11 LGRGVSSVVRRCIHKPTRQEYAVKIIDitgGGSFSPEEVQElreatlkEIDILRKVSgHPNIIQLKDTYETNTFFFLVFD 90


                   ...
gi 1907111731 2875 ILR 2877
Cdd:cd14182     91 LMK 93
 
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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