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Conserved domains on  [gi|4757980|ref|NP_004058|]
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beta-chimaerin isoform 2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
275-468 1.09e-139

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


:

Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 398.81  E-value: 1.09e-139
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  275 YCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKL 354
Cdd:cd04372   1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  355 YFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPT 434
Cdd:cd04372  81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160
                       170       180       190
                ....*....|....*....|....*....|....
gi 4757980  435 LMRPPEDSTLTTLHDMRYQKLIVQILIENEDVLF 468
Cdd:cd04372 161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
52-138 1.32e-43

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198215  Cd Length: 91  Bit Score: 148.28  E-value: 1.32e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   52 RPKYYGREFHGIISREQADELLGG-VEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK---HFVGEKRFESIHDLV 127
Cdd:cd10352   1 RPRFYGREYHGLISREEAEQLLSGaSDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKnhyHYVGEKRFDTIHDLV 80
                        90
                ....*....|.
gi 4757980  128 TDGLITLYIET 138
Cdd:cd10352  81 ADGLITLYMET 91
C1_betaCHN cd20857
protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; ...
210-270 9.36e-43

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


:

Pssm-ID: 410407  Cd Length: 61  Bit Score: 145.18  E-value: 9.36e-43
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980  210 NYEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 270
Cdd:cd20857   1 NYEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 61
 
Name Accession Description Interval E-value
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
275-468 1.09e-139

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 398.81  E-value: 1.09e-139
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  275 YCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKL 354
Cdd:cd04372   1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  355 YFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPT 434
Cdd:cd04372  81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160
                       170       180       190
                ....*....|....*....|....*....|....
gi 4757980  435 LMRPPEDSTLTTLHDMRYQKLIVQILIENEDVLF 468
Cdd:cd04372 161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
289-464 4.14e-64

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 204.81  E-value: 4.14e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980     289 QRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVypDINIITGALKLYFRDLPIPVITYDT 368
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY--DVHDVAGLLKLFLRELPEPLITYEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980     369 YSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPeDSTLTTLH 448
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPP-DGEVASLK 158
                          170
                   ....*....|....*.
gi 4757980     449 DMRYQKLIVQILIENE 464
Cdd:smart00324 159 DIRHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
291-439 1.08e-60

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 195.07  E-value: 1.08e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980    291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVypDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDLEEE--DVHVVASLLKLFLRELPEPLLTFELYE 78
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4757980    371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPP 439
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
52-138 1.32e-43

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 148.28  E-value: 1.32e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   52 RPKYYGREFHGIISREQADELLGG-VEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK---HFVGEKRFESIHDLV 127
Cdd:cd10352   1 RPRFYGREYHGLISREEAEQLLSGaSDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKnhyHYVGEKRFDTIHDLV 80
                        90
                ....*....|.
gi 4757980  128 TDGLITLYIET 138
Cdd:cd10352  81 ADGLITLYMET 91
C1_betaCHN cd20857
protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; ...
210-270 9.36e-43

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410407  Cd Length: 61  Bit Score: 145.18  E-value: 9.36e-43
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980  210 NYEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 270
Cdd:cd20857   1 NYEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 61
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
215-267 5.05e-21

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 395079  Cd Length: 53  Bit Score: 85.96  E-value: 5.05e-21
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 4757980    215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPD 267
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPECGCD 53
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
60-127 5.82e-17

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 75.73  E-value: 5.82e-17
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4757980      60 FHGIISREQADELL-GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK---HFVGEKRFESIHDLV 127
Cdd:smart00252   4 YHGFISREEAEKLLkNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDgkfYLEGGRKFPSLVELV 75
SH2 pfam00017
SH2 domain;
60-128 8.72e-16

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 71.86  E-value: 8.72e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4757980     60 FHGIISREQADELL--GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFH--DGKHFV-GEKRFESIHDLVT 128
Cdd:pfam00017   2 YHGKISRQEAERLLlnGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQStdNGGYYIsGGVKFSSLAELVE 75
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
215-264 1.35e-15

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 70.57  E-value: 1.35e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 4757980     215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50
 
Name Accession Description Interval E-value
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
275-468 1.09e-139

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 398.81  E-value: 1.09e-139
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  275 YCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKL 354
Cdd:cd04372   1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  355 YFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPT 434
Cdd:cd04372  81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160
                       170       180       190
                ....*....|....*....|....*....|....
gi 4757980  435 LMRPPEDSTLTTLHDMRYQKLIVQILIENEDVLF 468
Cdd:cd04372 161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
289-464 4.14e-64

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 204.81  E-value: 4.14e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980     289 QRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVypDINIITGALKLYFRDLPIPVITYDT 368
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY--DVHDVAGLLKLFLRELPEPLITYEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980     369 YSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPeDSTLTTLH 448
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPP-DGEVASLK 158
                          170
                   ....*....|....*.
gi 4757980     449 DMRYQKLIVQILIENE 464
Cdd:smart00324 159 DIRHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
291-439 1.08e-60

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 195.07  E-value: 1.08e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980    291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVypDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDLEEE--DVHVVASLLKLFLRELPEPLLTFELYE 78
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4757980    371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPP 439
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
291-463 2.99e-60

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.


Pssm-ID: 238090 [Multi-domain]  Cd Length: 169  Bit Score: 194.83  E-value: 2.99e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISanvYPDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLE---DYDVHDVASLLKLYLRELPEPLIPFELYD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPeDSTLTTLHDM 450
Cdd:cd00159  78 EFIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPP-DSDDELLEDI 156
                       170
                ....*....|...
gi 4757980  451 RYQKLIVQILIEN 463
Cdd:cd00159 157 KKLNEIVEFLIEN 169
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
291-468 8.14e-52

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239863  Cd Length: 192  Bit Score: 173.36  E-value: 8.14e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKAD-ISANVY-PDINIITGALKLYFRDLPIPVITYDT 368
Cdd:cd04398  17 PNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLlISPEDYeSDIHSVASLLKLFFRELPEPLLTKAL 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  369 YSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDStlttLH 448
Cdd:cd04398  97 SREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDN----AA 172
                       170       180
                ....*....|....*....|
gi 4757980  449 DMRYQKLIVQILIENEDVLF 468
Cdd:cd04398 173 DMSFQSRVIETLLDNAYQIF 192
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
291-468 5.64e-51

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239860  Cd Length: 196  Bit Score: 171.43  E-value: 5.64e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04395  19 PLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELYP 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDSTLTTLHDM 450
Cdd:cd04395  99 DFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMETMVTHM 178
                       170
                ....*....|....*...
gi 4757980  451 RYQKLIVQILIENEDVLF 468
Cdd:cd04395 179 PDQCKIVETLIQHYDWFF 196
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
277-463 1.63e-50

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 169.88  E-value: 1.63e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  277 CDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDgEKADISANVYPDINIITGALKLYF 356
Cdd:cd04403   3 CHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHD-EKLDLDDSKWEDIHVITGALKLFF 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  357 RDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLM 436
Cdd:cd04403  82 RELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLL 161
                       170       180
                ....*....|....*....|....*..
gi 4757980  437 RPPEDSTLTTLHdMRYQKLIVQILIEN 463
Cdd:cd04403 162 RPEQETGNIAVH-MVYQNQIVELILLE 187
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
292-463 1.23e-44

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239839  Cd Length: 203  Bit Score: 154.86  E-value: 1.23e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  292 MVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAF--DRDGEKADIS-ANVYPDINIITGALKLYFRDLPIPVITYDT 368
Cdd:cd04374  30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGldPKTSTPGDVDlDNSEWEIKTITSALKTYLRNLPEPLMTYEL 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  369 YSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDsTLTTLH 448
Cdd:cd04374 110 HNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEE-TVAAIM 188
                       170
                ....*....|....*
gi 4757980  449 DMRYQKLIVQILIEN 463
Cdd:cd04374 189 DIKFQNIVVEILIEN 203
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
278-463 1.51e-44

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239843  Cd Length: 203  Bit Score: 154.89  E-value: 1.51e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  278 DLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDIniiTGALKLYFR 357
Cdd:cd04378   4 DFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDI---SSVLKLFLR 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  358 DLPIPVITYDTYSKFIDAAK-ISNADERLEA-------------VHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMN 423
Cdd:cd04378  81 QLPEPLILFRLYNDFIALAKeIQRDTEEDKApntpievnriirkLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMS 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 4757980  424 AENLGIVFGPTLMRP---PEDSTLTTLHDMRYQKLIVQILIEN 463
Cdd:cd04378 161 PNNLGIVFGPTLIRPrpgDADVSLSSLVDYGYQARLVEFLITN 203
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
52-138 1.32e-43

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 148.28  E-value: 1.32e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   52 RPKYYGREFHGIISREQADELLGG-VEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK---HFVGEKRFESIHDLV 127
Cdd:cd10352   1 RPRFYGREYHGLISREEAEQLLSGaSDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKnhyHYVGEKRFDTIHDLV 80
                        90
                ....*....|.
gi 4757980  128 TDGLITLYIET 138
Cdd:cd10352  81 ADGLITLYMET 91
C1_betaCHN cd20857
protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; ...
210-270 9.36e-43

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410407  Cd Length: 61  Bit Score: 145.18  E-value: 9.36e-43
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980  210 NYEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 270
Cdd:cd20857   1 NYEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 61
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
291-463 3.38e-42

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239838  Cd Length: 185  Bit Score: 147.99  E-value: 3.38e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEkADISANVYPdINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04373  16 PIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHN-LDLVSKDFT-VNAVAGALKSFFSELPDPLIPYSMHL 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRpPEDSTLTTLHDM 450
Cdd:cd04373  94 ELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR-PDFTSMEALSAT 172
                       170
                ....*....|...
gi 4757980  451 RYQKLIVQILIEN 463
Cdd:cd04373 173 RIYQTIIETFIQQ 185
C1_CHN cd20806
protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are ...
215-266 2.93e-38

protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410356  Cd Length: 53  Bit Score: 132.82  E-value: 2.93e-38
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20806   2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
278-463 3.13e-38

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239873  Cd Length: 200  Bit Score: 138.03  E-value: 3.13e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  278 DLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDIniiTGALKLYFR 357
Cdd:cd04408   4 DFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHDI---TSVLKHFLK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  358 DLPIPVITYDTYSKFIDAAKISNAD------------ERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAE 425
Cdd:cd04408  81 ELPEPVLPFQLYDDFIALAKELQRDsekaaespsiveNIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPN 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 4757980  426 NLGIVFGPTLMRPP--EDSTLTTLHDMRYQKLIVQILIEN 463
Cdd:cd04408 161 NLGIVFGPTLLRPLvgGDVSMICLLDTGYQAQLVEFLISN 200
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
287-462 3.81e-38

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239842  Cd Length: 186  Bit Score: 137.18  E-value: 3.81e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  287 NTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISAnvYPdINIITGALKLYFRDLPIPVITY 366
Cdd:cd04377  12 DRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLED--YP-IHVITSVLKQWLRELPEPLMTF 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  367 DTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDS-TLT 445
Cdd:cd04377  89 ELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCPDTAdPLQ 168
                       170
                ....*....|....*..
gi 4757980  446 TLHDMRYQKLIVQILIE 462
Cdd:cd04377 169 SLQDVSKTTTCVETLIK 185
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
279-461 9.15e-38

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 136.60  E-value: 9.15e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  279 LTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEkaDISANVYP-DINIITGALKLYFR 357
Cdd:cd04387   5 ISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNK--DVSVMLSEmDVNAIAGTLKLYFR 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  358 DLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMR 437
Cdd:cd04387  83 ELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLR 162
                       170       180
                ....*....|....*....|....*..
gi 4757980  438 PPE---DSTLTTLHDMRYQKLIVQILI 461
Cdd:cd04387 163 PSEkesKIPTNTMTDSWSLEVMSQVQV 189
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
273-440 1.06e-37

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 136.48  E-value: 1.06e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  273 KVYCCDLTTLVKAHNTQRPMVVDICIREIEARGLkSEGLYRVSGFTEHIEDVKMAFDRDGEkADISANVY-PDINIITGA 351
Cdd:cd04384   1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQI-PDLTKDVYiQDIHSVSSL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  352 LKLYFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVF 431
Cdd:cd04384  79 CKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVW 158

                ....*....
gi 4757980  432 GPTLMRPPE 440
Cdd:cd04384 159 APNLLRSKQ 167
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
291-463 7.17e-36

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 130.89  E-value: 7.17e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDgekadiSANVYPDIN-----IITGALKLYFRDLPIPVIT 365
Cdd:cd04385  16 PVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKD------ARSVQLREGeytvhDVADVLKRFLRDLPDPLLT 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  366 YDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDSTLT 445
Cdd:cd04385  90 SELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQ 169
                       170
                ....*....|....*...
gi 4757980  446 TLHDMRyqklIVQILIEN 463
Cdd:cd04385 170 TSHEVK----VIEDLIDN 183
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
290-462 1.26e-35

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239847  Cd Length: 193  Bit Score: 130.49  E-value: 1.26e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  290 RPMVVDI---CIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISaNVypDINIITGALKLYFRDLPIPVITY 366
Cdd:cd04382  14 SPMIPALivhCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLS-KV--DIHVICGCLKDFLRSLKEPLITF 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  367 DTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVtMNEKDNFMNAENLGIVFGPTLM--RPPEDSTL 444
Cdd:cd04382  91 ALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARVFGPTIVgySVPNPDPM 169
                       170
                ....*....|....*...
gi 4757980  445 TTLHDMRYQKLIVQILIE 462
Cdd:cd04382 170 TILQDTVRQPRVVERLLE 187
C1_alphaCHN cd20856
protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; ...
211-266 1.83e-35

protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; Alpha-chimaerin, also called A-chimaerin, N-chimaerin (CHN), alpha-chimerin, N-chimerin (NC), or Rho GTPase-activating protein 2 (ARHGAP2), is a GTPase-activating protein (GAP) for p21-rac and a phorbol ester receptor. It is involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance. Alpha-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410406  Cd Length: 57  Bit Score: 125.57  E-value: 1.83e-35
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4757980  211 YEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20856   2 YEKVHNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKP 57
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
278-461 8.21e-34

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239874  Cd Length: 211  Bit Score: 126.46  E-value: 8.21e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  278 DLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISaNVYPdiNIITGALKLYFR 357
Cdd:cd04409   4 DFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELS-ELSP--HDISNVLKLYLR 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  358 DLPIPVITYDTYSKFIDAAK-ISNADERLEA---------------------VHEVLMLLPPAHYETLRYLMIHLKKVTM 415
Cdd:cd04409  81 QLPEPLILFRLYNEFIGLAKeSQHVNETQEAkknsdkkwpnmctelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRVSE 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 4757980  416 NEKDNFMNAENLGIVFGPTLMRP-PEDST--LTTLHDMRYQKLIVQILI 461
Cdd:cd04409 161 QAEENKMSASNLGIIFGPTLIRPrPTDATvsLSSLVDYPHQARLVELLI 209
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
272-468 1.68e-32

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239851  Cd Length: 203  Bit Score: 122.57  E-value: 1.68e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  272 KKVYCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADIsANVYPDINIITGA 351
Cdd:cd04386   2 KPVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPL-DEFYSDPHAVASA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  352 LKLYFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVF 431
Cdd:cd04386  81 LKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVL 160
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 4757980  432 GPTLMRPPEDSTLTTLHDMR--YQKLIVQILIENEDVLF 468
Cdd:cd04386 161 APNLLWAKNEGSLAEMAAGTsvHVVAIVELIISHADWFF 199
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
291-461 5.55e-32

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 120.48  E-value: 5.55e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISAnvYPdINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04407  16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLEN--YP-IHAITGLLKQWLRELPEPLMTFAQYN 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDST-LTTLHD 449
Cdd:cd04407  93 DFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDSSDpLTSMKD 172
                       170
                ....*....|..
gi 4757980  450 MRYQKLIVQILI 461
Cdd:cd04407 173 VAKTTTCVEMLI 184
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
278-441 1.78e-31

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239848  Cd Length: 188  Bit Score: 119.45  E-value: 1.78e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  278 DLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRdGEKADISANVYPDINIITGALKLYFR 357
Cdd:cd04383   6 SLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFER-GEDPLADDQNDHDINSVAGVLKLYFR 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  358 DLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMR 437
Cdd:cd04383  85 GLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMP 164

                ....
gi 4757980  438 PPED 441
Cdd:cd04383 165 VPEG 168
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
278-451 5.79e-31

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239844  Cd Length: 207  Bit Score: 118.34  E-value: 5.79e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  278 DLTTLVKAHNTQR--PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKLY 355
Cdd:cd04379   4 PLSRLVEREGESRdvPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVLKDY 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  356 FRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLML---LPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFG 432
Cdd:cd04379  84 LRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSIidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFG 163
                       170       180
                ....*....|....*....|..
gi 4757980  433 PTLMRP---PEDSTLTTLHDMR 451
Cdd:cd04379 164 PVLMFCsqeFSRYGISPTSKMA 185
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
279-468 2.34e-30

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239869 [Multi-domain]  Cd Length: 195  Bit Score: 116.28  E-value: 2.34e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  279 LTTLVKAHNTQR--PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRdGEKADISAnvYPDINIITGALKLYF 356
Cdd:cd04404  10 LQFLKEKNPEQEpiPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNM-GEPVDFDQ--YEDVHLPAVILKTFL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  357 RDLPIPVITYDTYSKFIDAAKISNaDERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLM 436
Cdd:cd04404  87 RELPEPLLTFDLYDDIVGFLNVDK-EERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLL 165
                       170       180       190
                ....*....|....*....|....*....|..
gi 4757980  437 RPPEDStlTTLHDMRYQKLIVQILIENEDVLF 468
Cdd:cd04404 166 WAKDAS--MSLSAINPINTFTKFLLDHQDEIF 195
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
286-468 9.95e-29

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239841  Cd Length: 206  Bit Score: 112.53  E-value: 9.95e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  286 HNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGekaDISANVYPDINIITGALKLYFRDLPIPVIT 365
Cdd:cd04376   5 IARQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGI---DVVLDENHSVHDVAALLKEFFRDMPDPLLP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  366 YDTYSKFIDAAKIsNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKD-----------NFMNAENLGIVFGPT 434
Cdd:cd04376  82 RELYTAFIGTALL-EPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPN 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 4757980  435 LMRPPEDSTLT------TLHDMRYQKLIVQILIENEDVLF 468
Cdd:cd04376 161 LLHKQKSGEREfvqaslRIEESTAIINVVQTMIDNYEELF 200
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
291-468 1.10e-25

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 103.68  E-value: 1.10e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRdGEKADISANVypDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04390  23 PILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDA-GERPSFDSDT--DVHTVASLLKLYLRELPEPVIPWAQYE 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADErlEAVHEVLM----LLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDSTLTT 446
Cdd:cd04390 100 DFLSCAQLLSKDE--EKGLGELMkqvsILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPKVEDPATI 177
                       170       180
                ....*....|....*....|....*
gi 4757980  447 lhdMRYQKLIVQ---ILIENEDVLF 468
Cdd:cd04390 178 ---MEGTPQIQQlmtVMISKHEPLF 199
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
292-463 7.54e-25

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239859 [Multi-domain]  Cd Length: 202  Bit Score: 101.39  E-value: 7.54e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  292 MVVDICiREIEARgLKSEGLYRVSGFTEHIEDVKMAFDrDGEKADISANvypdINIITGALKLYFRDLPIPVITYDTYSK 371
Cdd:cd04394  23 FLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLE-GGEACLSSAL----PCDVAGLLKQFFRELPEPLLPYDLHEA 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  372 FIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPED-STLTTLHDM 450
Cdd:cd04394  96 LLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGgEKMSSSTEK 175
                       170
                ....*....|....*
gi 4757980  451 RYQKL--IVQILIEN 463
Cdd:cd04394 176 RLRLQaaVVQTLIDN 190
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
291-435 8.59e-25

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 100.90  E-value: 8.59e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEA-RGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKLYFRDLPIPVITYDTY 369
Cdd:cd04400  23 PSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLFSSSLYPDVHTVAGLLKLYLRELPTLILGGELH 102
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4757980  370 SKFIDAAKI-SNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTL 435
Cdd:cd04400 103 NDFKRLVEEnHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNVCIVFSPTL 169
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
291-435 1.22e-24

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 100.20  E-value: 1.22e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGekaDISANVYpDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04381  21 PLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRE---SPNLEEY-EPPTVASLLKQYLRELPEPLLTKELMP 96
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTL 435
Cdd:cd04381  97 RFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLSPTV 161
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
291-461 1.82e-24

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239871  Cd Length: 186  Bit Score: 100.08  E-value: 1.82e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANvypDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04406  16 PLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNLDDY---NIHVIASVFKQWLRDLPNPLMTFELYE 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDS-TLTTLHD 449
Cdd:cd04406  93 EFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDTTdPLQSVQD 172
                       170
                ....*....|..
gi 4757980  450 MRYQKLIVQILI 461
Cdd:cd04406 173 ISKTTTCVELIV 184
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
274-435 6.05e-23

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239856  Cd Length: 216  Bit Score: 96.65  E-value: 6.05e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  274 VYCCDLTTLV-----KAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRD-GEKADISANVYPdiNI 347
Cdd:cd04391   1 LFGVPLSTLLerdqkKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKfYEGTFLWDQVKQ--HD 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  348 ITGALKLYFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENL 427
Cdd:cd04391  79 AASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNV 158

                ....*...
gi 4757980  428 GIVFGPTL 435
Cdd:cd04391 159 AMIMAPNL 166
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
215-267 5.05e-21

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 395079  Cd Length: 53  Bit Score: 85.96  E-value: 5.05e-21
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 4757980    215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPD 267
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPECGCD 53
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
291-463 2.11e-20

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 88.67  E-value: 2.11e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDrDGEKADISANvyPDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04393  21 PAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLD-SGEEVDLSKE--ADVCSAASLLRLFLQELPEGLIPASLQI 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDA-AKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDstlttLHD 449
Cdd:cd04393  98 RLMQLyQDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFGPDVFHVYTD-----VED 172
                       170
                ....*....|....*..
gi 4757980  450 MRYQKLIVQI---LIEN 463
Cdd:cd04393 173 MKEQEICSRImakLLEN 189
C1_cPKC_nPKC_rpt2 cd20793
second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ...
215-264 2.02e-19

second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410343  Cd Length: 50  Bit Score: 81.56  E-value: 2.02e-19
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20793   1 HKFKVHTYYSPTFCDHCGSLLYGLVRQGLKCKDCGMNVHHRCKENVPHLC 50
C1_PKD_rpt1 cd20795
first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) ...
215-264 2.27e-19

first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) family; 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 are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410345  Cd Length: 56  Bit Score: 81.58  E-value: 2.27e-19
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20795   4 HSLFVHSYKSPTFCDFCGEMLFGLVRQGLKCEGCGLNFHKRCAYKIPNNC 53
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
291-468 2.85e-19

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239867  Cd Length: 192  Bit Score: 85.43  E-value: 2.85e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDrDGEKADISAnvYPdINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04402  16 PKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLN-SGVEVDLKA--EP-VLLLASVLKDFLRNIPGSLLSSDLYE 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDSTLTTlHDM 450
Cdd:cd04402  92 EWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLLWPPASSELQN-EDL 170
                       170
                ....*....|....*...
gi 4757980  451 RYQKLIVQILIENEDVLF 468
Cdd:cd04402 171 KKVTSLVQFLIENCQEIF 188
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
291-464 1.24e-18

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 83.77  E-value: 1.24e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDIcIREIEARGLKSEGLYRvSGFTEHIEDVKMAFDRDGEKADISANvypDINIITGALKLYFRDLPIPVITYDTYS 370
Cdd:cd04388  17 PLLIKL-VEAIEKKGLESSTLYR-TQSSSSLTELRQILDCDAASVDLEQF---DVAALADALKRYLLDLPNPVIPAPVYS 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  371 KFIDAAK-ISNADERLEAVHEVLM--LLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDSTLTTL 447
Cdd:cd04388  92 EMISRAQeVQSSDEYAQLLRKLIRspNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQPASSDSPE 171
                       170
                ....*....|....*..
gi 4757980  448 HDMRyqklIVQILIENE 464
Cdd:cd04388 172 FHIR----IIEVLITSE 184
C1 cd00029
protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich ...
215-264 1.39e-18

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.


Pssm-ID: 410341  Cd Length: 50  Bit Score: 79.10  E-value: 1.39e-18
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd00029   1 HRFVPTTFSSPTFCDVCGKLIWGLFKQGLKCSDCGLVCHKKCLDKAPSPC 50
C1_RASGRP cd20808
protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein ...
215-264 2.03e-18

protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410358  Cd Length: 52  Bit Score: 78.53  E-value: 2.03e-18
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20808   2 HNFQETTYFKPTFCDHCTGLLWGLIKQGYKCKDCGINCHKHCKDLVVVEC 51
C1_nPKC_theta-like_rpt2 cd20837
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
215-264 4.55e-18

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410387  Cd Length: 50  Bit Score: 77.48  E-value: 4.55e-18
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20837   1 HRFKVYNYMSPTFCDHCGSLLWGLFRQGLKCEECGMNVHHKCQKKVANLC 50
C1_PKD_rpt2 cd20796
second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D ...
215-264 7.30e-18

second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D (PKD); 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 are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410346  Cd Length: 54  Bit Score: 76.94  E-value: 7.30e-18
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20796   2 HTFVVHTYTKPTVCQHCKKLLKGLFRQGLQCKDCKFNCHKKCAEKVPKDC 51
C1_nPKC_epsilon-like_rpt2 cd20838
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
215-264 1.45e-17

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410388  Cd Length: 55  Bit Score: 76.16  E-value: 1.45e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20838   3 HRFSVHNYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRCQKNVANNC 52
C1_cPKC_rpt2 cd20836
second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ...
215-267 3.07e-17

second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410386  Cd Length: 54  Bit Score: 75.45  E-value: 3.07e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPD 267
Cdd:cd20836   1 HKFKVHTYSSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKRCVKNVPSLCGTD 53
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
60-127 5.82e-17

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 75.73  E-value: 5.82e-17
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4757980      60 FHGIISREQADELL-GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK---HFVGEKRFESIHDLV 127
Cdd:smart00252   4 YHGFISREEAEKLLkNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDgkfYLEGGRKFPSLVELV 75
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
272-435 1.17e-16

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239840  Cd Length: 220  Bit Score: 78.61  E-value: 1.17e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  272 KKVYCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKA---DISANVYPDInii 348
Cdd:cd04375   2 KNVFGVPLLVNLQRTGQPLPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRSMIESSTDNVnydGQQAYDVADM--- 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  349 tgaLKLYFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLG 428
Cdd:cd04375  79 ---LKQYFRDLPEPLLTNKLSETFIAIFQYVPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLA 155

                ....*..
gi 4757980  429 IVFGPTL 435
Cdd:cd04375 156 VCLAPSL 162
C1_PKD3_rpt1 cd20841
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ...
213-270 8.29e-16

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410391  Cd Length: 75  Bit Score: 72.00  E-value: 8.29e-16
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 270
Cdd:cd20841   9 RPHTLYVHSYKAPTFCDYCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRKR 66
SH2 pfam00017
SH2 domain;
60-128 8.72e-16

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 71.86  E-value: 8.72e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4757980     60 FHGIISREQADELL--GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFH--DGKHFV-GEKRFESIHDLVT 128
Cdd:pfam00017   2 YHGKISRQEAERLLlnGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQStdNGGYYIsGGVKFSSLAELVE 75
C1_MTMR-like cd20828
protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to ...
215-264 1.22e-15

protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to myotubularin-related proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs), such as MTMR5 and MTMR13. MTMRs may function as guanine nucleotide exchange factors (GEFs). Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410378  Cd Length: 57  Bit Score: 70.94  E-value: 1.22e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20828   6 HNFEPHSFVTPTNCDYCLQILWGIVKKGMKCSECGYNCHEKCQPQVPKQC 55
C1_Sbf-like cd20827
protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf ...
214-265 1.25e-15

protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf and similar proteins; This group includes Drosophila melanogaster SET domain binding factor (Sbf), the single homolog of human MTMR5/MTMR13, and similar proteins, that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs) which may function as guanine nucleotide exchange factors (GEFs). Sbf is a pseudophosphatase that coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. It also functions as a GEF that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410377  Cd Length: 53  Bit Score: 70.91  E-value: 1.25e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  214 THNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20827   1 PHRFEKHNFTTPTYCDYCSSLLWGLVKTGMRCADCGYSCHEKCLEHVPKNCT 52
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
215-264 1.35e-15

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 70.57  E-value: 1.35e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 4757980     215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50
C1_SpBZZ1-like cd20824
protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein ...
215-264 4.76e-15

protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein BZZ1 and similar proteins; BZZ1 is a syndapin-like F-BAR protein that plays a role in endocytosis and trafficking to the vacuole. It functions with type I myosins to restore polarity of the actin cytoskeleton after NaCl stress. BZZ1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. Schizosaccharomyces pombe BZZ1 also harbors a C1 domain, but Saccharomyces cerevisiae BZZ1 doesn't have any. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410374  Cd Length: 53  Bit Score: 69.27  E-value: 4.76e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20824   2 HNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKCELKVPPEC 51
C1_RASGRP1 cd20860
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 ...
215-265 5.15e-15

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410410  Cd Length: 55  Bit Score: 69.19  E-value: 5.15e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20860   3 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECK 53
C1_PKD1_rpt1 cd20839
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ...
213-270 6.48e-15

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410389  Cd Length: 72  Bit Score: 69.28  E-value: 6.48e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 270
Cdd:cd20839   6 RPHALFVHSYRAPAFCDHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRKR 63
C1_MRCK cd20809
protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related ...
215-264 9.93e-15

protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410359  Cd Length: 53  Bit Score: 68.07  E-value: 9.93e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20809   1 HKFIVRTFSTPTKCNHCTSLMVGLVRQGLVCEVCGYACHVSCADKAPQVC 50
C1_PKD2_rpt2 cd20843
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ...
215-264 1.01e-14

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410393  Cd Length: 79  Bit Score: 69.23  E-value: 1.01e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20843  12 HTFVIHSYTRPTVCQFCKKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDC 61
C1_PKD2_rpt1 cd20840
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ...
213-270 1.16e-14

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410390  Cd Length: 73  Bit Score: 68.93  E-value: 1.16e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 270
Cdd:cd20840   9 RPHALNVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRCAFSIPNNCSGARKR 66
C1_RASGRP4 cd20863
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 ...
215-265 1.40e-14

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 (RASGRP4) and similar proteins; RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. It may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410413  Cd Length: 57  Bit Score: 67.88  E-value: 1.40e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20863   4 HNFHETTFKKPTFCDSCSGFLWGVTKQGYRCQDCGINCHKHCKDQVDVECK 54
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
305-463 2.38e-14

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239854  Cd Length: 187  Bit Score: 71.27  E-value: 2.38e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  305 GLKSEGLYRVSGFTEHIEDVKMAFDRdgekADISANVYPDINIITGALKLYFRDLPIPVITYDTYSKFIDaakisNADER 384
Cdd:cd04389  37 GFQTEGIFRVPGDIDEVNELKLRVDQ----WDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQQCIS-----ASEDP 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  385 LEAVhEVLMLLPPAHYETLRYLmIHLKKV---TMNEKDNFMNAENLGIVFGPTLMRPPEDSTLTTLHDMRYQKLIVQILI 461
Cdd:cd04389 108 DKAV-EIVQKLPIINRLVLCYL-INFLQVfaqPENVAHTKMDVSNLAMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLI 185

                ..
gi 4757980  462 EN 463
Cdd:cd04389 186 EH 187
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
291-465 3.05e-14

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239862  Cd Length: 213  Bit Score: 71.63  E-value: 3.05e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEK-ADISANvypdiNIITGA--LKLYFRDLPIPVITYD 367
Cdd:cd04397  28 PALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKNPTEvPDLSKE-----NPVQLAalLKKFLRELPDPLLTFK 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  368 TYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTM-----NEKDNFMNAENLGIVFGPTLMRpPEDS 442
Cdd:cd04397 103 LYRLWISSQKIEDEEERKRVLHLVYCLLPKYHRDTMEVLFSFLKWVSSfshidEETGSKMDIHNLATVITPNILY-SKTD 181
                       170       180
                ....*....|....*....|...
gi 4757980  443 TLTTLHDMRYQKLIVQILIENED 465
Cdd:cd04397 182 NPNTGDEYFLAIEAVNYLIENNE 204
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
60-128 3.20e-14

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 67.48  E-value: 3.20e-14
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4757980   60 FHGIISREQADELL-GGVEGAYILRESQRQPGCYTLALRFG-NQTLNYRLFHDGKHFVG----EKRFESIHDLVT 128
Cdd:cd00173   3 FHGSISREEAERLLrGKPDGTFLVRESSSEPGDYVLSVRSGdGKVKHYLIERNEGGYYLlggsGRTFPSLPELVE 77
C1_VAV cd20810
protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function ...
213-265 8.64e-14

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410360  Cd Length: 52  Bit Score: 65.36  E-value: 8.64e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNdCQ 265
Cdd:cd20810   1 TGHSFELTTFKEPTTCSVCKKLLKGLFFQGYKCSVCGAAVHKECIAKVKR-CG 52
C1_cPKC_nPKC_rpt1 cd20792
first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ...
215-265 1.92e-13

first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410342  Cd Length: 53  Bit Score: 64.57  E-value: 1.92e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20792   2 HKFVATFFKQPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKCP 52
C1_CeDKF1-like_rpt2 cd20798
second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ...
215-265 1.96e-13

second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410348  Cd Length: 54  Bit Score: 64.44  E-value: 1.96e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20798   2 HTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKCASLLPSNCR 52
C1_PIK3R-like_rpt2 cd20830
second protein kinase C conserved region 1 (C1 domain) found in uncharacterized ...
215-266 2.04e-13

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410380  Cd Length: 52  Bit Score: 64.58  E-value: 2.04e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20830   1 HRFVEQSFSTLQWCDKCGKFLFGLVHQGLQCQDCGLVCHRTCAATGLPKCEP 52
C1_PKD3_rpt2 cd20844
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ...
215-264 3.76e-13

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410394  Cd Length: 69  Bit Score: 64.26  E-value: 3.76e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20844   6 HTFAVHSYTRPTICQYCKRLLKGLFRQGMQCKDCRFNCHKRCASKVPRDC 55
C1_RASGRP3 cd20862
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 ...
215-256 3.84e-13

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410412  Cd Length: 59  Bit Score: 63.90  E-value: 3.84e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQC 256
Cdd:cd20862   8 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQC 49
C1_PKD1_rpt2 cd20842
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ...
215-264 5.26e-13

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410392  Cd Length: 94  Bit Score: 64.65  E-value: 5.26e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20842  35 HTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNC 84
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
60-142 7.21e-13

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 64.23  E-value: 7.21e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELLGGVE-GAYILRESQRQPGCYTLALRFGNQTLNYR-LFHDGKHFVGEKR-FESIHDLV------TDG 130
Cdd:cd09937   6 FHGKISREEAERLLQPPEdGLFLVRESTNYPGDYTLCVSFEGKVEHYRvIYRNGKLTIDEEEyFENLIQLVehytkdADG 85
                        90
                ....*....|..
gi 4757980  131 LITLYIETKAAE 142
Cdd:cd09937  86 LCTRLVKPKVKE 97
C1_nPKC_theta-like_rpt1 cd20834
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
213-264 2.27e-12

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410384  Cd Length: 61  Bit Score: 61.96  E-value: 2.27e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20834   6 KGHEFIAKFFRQPTFCSVCKEFLWGFNKQGYQCRQCNAAVHKKCHDKILGKC 57
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
291-467 3.54e-12

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239861  Cd Length: 225  Bit Score: 65.89  E-value: 3.54e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  291 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFD---RDGEKADISA-NVYPDINIitgaLKLYFRDLPIPVITY 366
Cdd:cd04396  33 PVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFStppDYGKSFDWDGyTVHDAASV----LRRYLNNLPEPLVPL 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  367 DTYSKF-----------------IDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGI 429
Cdd:cd04396 109 DLYEEFrnplrkrprilqymkgrINEPLNTDIDQAIKEYRDLITRLPNLNRQLLLYLLDLLAVFARNSDKNLMTASNLAA 188
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 4757980  430 VFGPTLMRPPEdstlttlHDM-----RYQKLIVQILIENEDVL 467
Cdd:cd04396 189 IFQPGILSHPD-------HEMdpkeyKLSRLVVEFLIEHQDKF 224
C1_Munc13 cd20807
protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene ...
215-264 8.79e-12

protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene family encodes a family of neuron-specific, synaptic molecules that bind to syntaxin, an essential mediator of neurotransmitter release. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410357  Cd Length: 53  Bit Score: 59.80  E-value: 8.79e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20807   1 HNFEVWTATTPTYCYECEGLLWGIARQGVRCTECGVKCHEKCKDLLNADC 50
C1_Stac cd20817
protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich ...
215-266 8.86e-12

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410367  Cd Length: 51  Bit Score: 59.65  E-value: 8.86e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPnDCQP 266
Cdd:cd20817   1 HSFQEHTFKKPTFCDVCKELLVGLSKQGLRCKNCKMNVHHKCQEGVP-DCSG 51
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
60-134 1.11e-11

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 60.86  E-value: 1.11e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELLG-GVEGAYILRESQRQPGCYTLALRFGNQTLNYRL--FHDGKHFV-GEKRFESIHDLV------TD 129
Cdd:cd09935   6 YHGPISRNAAEYLLSsGINGSFLVRESESSPGQYSISLRYDGRVYHYRIseDSDGKVYVtQEHRFNTLAELVhhhsknAD 85

                ....*
gi 4757980  130 GLITL 134
Cdd:cd09935  86 GLITT 90
C1_CeDKF1-like_rpt1 cd20797
first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ...
215-264 1.49e-11

first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410347  Cd Length: 56  Bit Score: 59.41  E-value: 1.49e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20797   4 HVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRCANAPRNNC 53
C1_Munc13-1 cd20858
protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; ...
215-264 3.47e-11

protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; Munc13-1, also called protein unc-13 homolog A (Unc13A), is a diacylglycerol (DAG) receptor that plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410408  Cd Length: 60  Bit Score: 58.56  E-value: 3.47e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20858   8 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 57
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
60-127 4.52e-11

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 58.59  E-value: 4.52e-11
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4757980   60 FHGIISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDG--KHFVGEKRFESIHDLV 127
Cdd:cd10354   3 FHGKISREEAYNMLVkvGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIIPTGnnQFMMGGRYFSSLDDVI 74
C1_RASSF1 cd20885
protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing ...
215-265 1.50e-10

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 1 (RASSF1) and similar proteins; RASSF1 is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410435  Cd Length: 54  Bit Score: 56.51  E-value: 1.50e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20885   4 HDFQPCSLTNPTWCDLCGDFIWGLYKQCLRCTHCKYTCHLRCRDLVTLDCS 54
C1_DGKtheta_typeV_rpt1 cd20803
first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ...
215-264 1.68e-10

first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410353  Cd Length: 56  Bit Score: 56.16  E-value: 1.68e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20803   2 HSFRKKTFHKPTYCHHCTDLLWGLLNQGYQCEVCNFVSHERCLKTVVTPC 51
C1_ARHGEF-like cd20832
protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine ...
215-265 1.80e-10

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410382  Cd Length: 53  Bit Score: 56.23  E-value: 1.80e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20832   2 HQFVLQHYYQVTFCNHCSGLLWGIGYQGYQCSDCEFNIHKQCIEVIEESCP 52
C1_TNS2-like cd20826
protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; ...
213-266 2.69e-10

protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; The TNS2-like group includes TNS2, and variants of TNS1 and TNS3. Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity and interferes with AKT1 signaling. Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. Typical TNS1 and TNS3 do not contain C1 domains, but some isoforms/variants do. Members of this family contain an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410376  Cd Length: 52  Bit Score: 55.47  E-value: 2.69e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGliaQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20826   1 KSHSFKEKSFRKPRTCDVCKQIIWN---EGSSCRVCKYACHRKCEPKVTAACSP 51
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
306-441 3.56e-10

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239857  Cd Length: 208  Bit Score: 59.40  E-value: 3.56e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  306 LKSEGLYRVSGFTEHIEDVKMAFDR----DGEKADISANvypDINIItgaLKLYFRDLPIPVITYDTYSKFIDAAKISNA 381
Cdd:cd04392  24 LRVEGLFRKPGNSARQQELRDLLNSgtdlDLESGGFHAH---DCATV---LKGFLGELPEPLLTHAHYPAHLQIADLCQF 97
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4757980  382 DER------------LEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRP----PED 441
Cdd:cd04392  98 DEKgnktsapdkerlLEALQLLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLICPrnltPED 173
C1_MRCKalpha cd20864
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
213-264 7.76e-10

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCK alpha) and similar proteins; MRCK alpha, also called Cdc42-binding protein kinase alpha, DMPK-like alpha, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK alpha is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410414  Cd Length: 60  Bit Score: 54.64  E-value: 7.76e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20864   1 KAHQFVVKSFTTPTKCNQCTSLMVGLIRQGCTCEVCGFSCHVTCADKAPSVC 52
C1_RASGRP2 cd20861
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 ...
215-265 9.45e-10

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 (RASGRP2) and similar proteins; RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. It may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is also involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410411  Cd Length: 56  Bit Score: 54.12  E-value: 9.45e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20861   4 HNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECR 54
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
60-127 9.63e-10

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 55.35  E-value: 9.63e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4757980   60 FHGIISREQADELLGGV--EGAYILRESQRQPGCYTLALRFGNQTLNYRLFHD--GKHFVGEKRFESIHDLV 127
Cdd:cd09941   6 FHGKISRAEAEEILMNQrpDGAFLIRESESSPGDFSLSVKFGNDVQHFKVLRDgaGKYFLWVVKFNSLNELV 77
C1_Stac2 cd20881
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ...
213-260 1.28e-09

protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein 2 (Stac2) and similar proteins; Stac2, also called 24b2/Stac2, or Src homology 3 and cysteine-rich domain-containing protein 2, plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac2 contains a cysteine-rich C1 domain and one SH3 domain at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410431  Cd Length: 59  Bit Score: 54.07  E-value: 1.28e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHV 260
Cdd:cd20881   4 RTHSFQEHVFKKPSPCELCHQMIVGNSKQGLRCKMCKVSVHLWCSEEV 51
C1_RASSF1-like cd20820
protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing ...
215-264 2.44e-09

protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing protein 1 (RASSF1)-like family; The RASSF1-like family includes RASSF1 and RASSF5. RASSF1 and RASSF5 are members of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1; both are localized to microtubules and involved in the regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF1 and RASSF5 contain a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410370  Cd Length: 52  Bit Score: 52.83  E-value: 2.44e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20820   2 HRFVPLELEQPTWCDLCGSVILGLFRKCLRCANCKMTCHPRCRSLVCLTC 51
C1_aPKC cd20794
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ...
215-266 3.05e-09

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain one C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410344  Cd Length: 55  Bit Score: 52.65  E-value: 3.05e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20794   3 HLFQAKRFNRRAVCAYCSDRIWGLGRQGYKCINCKLLVHKKCHKLVKVACGQ 54
C1_Munc13-2-like cd20859
protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar ...
215-264 3.51e-09

protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins; Munc13-2, also called protein unc-13 homolog B (Unc13B), plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410409  Cd Length: 82  Bit Score: 53.53  E-value: 3.51e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20859  20 HNFEVWTATTPTYCYECEGLLWGIARQGMRCSECGVKCHEKCQDLLNADC 69
C1_Raf cd20811
protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated ...
214-265 3.94e-09

protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated Fibrosarcoma) kinase family; Raf kinases are serine/threonine kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. They act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410361  Cd Length: 49  Bit Score: 52.30  E-value: 3.94e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  214 THNFKVHTFRGPHWCEYCANFMWgliaQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20811   2 SHNFVRKTFFTLAFCDVCRKLLF----QGFRCQTCGFKFHQRCSDQVPALCE 49
C1_cPKC_rpt1 cd20833
first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ...
213-264 4.44e-09

first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410383  Cd Length: 58  Bit Score: 52.41  E-value: 4.44e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20833   1 KDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCSFVVHKRCHEFVTFSC 52
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
60-134 5.46e-09

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 52.77  E-value: 5.46e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGkhfvGEKRFESIHDLVTDGLITL 134
Cdd:cd10347   4 YHGKISREVAEALLlreGGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRHG----EDAFFSDDGPLIFHGLDTL 77
C1_ScPKC1-like_rpt2 cd20823
second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae ...
211-264 8.14e-09

second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410373  Cd Length: 59  Bit Score: 51.54  E-value: 8.14e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 4757980  211 YEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20823   1 HRIPHRFEPFTNLGANWCCHCGQMLPLGRKQIRKCTECGKTAHAQCAHLVPNFC 54
C1_nPKC_epsilon-like_rpt1 cd20835
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
215-264 1.92e-08

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410385  Cd Length: 64  Bit Score: 50.93  E-value: 1.92e-08
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIA-QGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20835  10 HKFMATYLRQPTYCSHCKDFIWGVIGkQGYQCQVCTCVVHKRCHQLVVTKC 60
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
60-105 2.77e-08

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 51.65  E-value: 2.77e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNY 105
Cdd:cd09944   8 FHGGISRDEAARLIrqqGLVDGVFLVRESQSNPGAFVLSLKHGQKIKHY 56
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
52-127 4.56e-08

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 50.59  E-value: 4.56e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4757980   52 RPKYYGRefhgiISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGKHF-VGEKRFESIHDLV 127
Cdd:cd09943   1 QPWYYGR-----ITRHQAETLLNehGHEGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVDNVYcIGQRKFHTMDELV 74
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
351-442 1.02e-07

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239845  Cd Length: 220  Bit Score: 52.34  E-value: 1.02e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  351 ALKLYFRDLPIPVITYDTYSKFIDAAKiSNADERLEAVHevlMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIV 430
Cdd:cd04380 110 ALLLFLESLPDPIIPYSLYERLLEAVA-NNEEDKRQVIR---ISLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATI 185
                        90
                ....*....|..
gi 4757980  431 FGPTLMRPPEDS 442
Cdd:cd04380 186 FGRVLLRDPPRA 197
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
60-127 1.08e-07

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 49.96  E-value: 1.08e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980   60 FHGIISREQADELLGGV--EGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGKHFV-GEKRFESIHDLV 127
Cdd:cd09932   7 FHANLTREQAEEMLMRVprDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQEGRLFViGTSQFESLVELV 77
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
60-127 1.31e-07

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 49.40  E-value: 1.31e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980   60 FHGIISREQADELL--GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGKHF-VGEKRFESIHDLV 127
Cdd:cd10355   9 YHGNLTRHAAEALLlsNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHVEYTGYSFkFGFNEFSSLQDFV 79
C1_MRCKgamma cd20866
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
215-261 1.65e-07

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase gamma (MRCK gamma) and similar proteins; MRCK gamma (MRCKG), also called Cdc42-binding protein kinase gamma, DMPK-like gamma, myotonic dystrophy protein kinase-like gamma, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed in heart and skeletal muscles. It may act as a downstream effector of Cdc42 in cytoskeletal reorganization and contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410416  Cd Length: 52  Bit Score: 47.83  E-value: 1.65e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVP 261
Cdd:cd20866   1 HTFKPKTFTSPTKCLRCTSLMVGLVRQGLACEACNYVCHVSCAEGAP 47
C1_PIK3R-like_rpt1 cd20829
first protein kinase C conserved region 1 (C1 domain) found in uncharacterized ...
215-266 1.68e-07

first protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410379  Cd Length: 53  Bit Score: 47.73  E-value: 1.68e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPND-CQP 266
Cdd:cd20829   1 HRLVDVYFVTPILCRHCKDYIWGKGKVGVRCEDCHACFHLVCAKYAAKHpCQR 53
C1_VAV2 cd20868
protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely ...
215-261 2.24e-07

protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410418  Cd Length: 58  Bit Score: 47.57  E-value: 2.24e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVP 261
Cdd:cd20868   6 HNFQMYTFDKTTNCKACKMLLRGTFYQGYYCSKCGAGAHKECLEVIP 52
C1_VAV3 cd20869
protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously ...
215-256 2.27e-07

protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410419  Cd Length: 59  Bit Score: 47.51  E-value: 2.27e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQC 256
Cdd:cd20869   9 HDFKMHTFERVTSCKVCQMLLRGTFYQGYLCSKCGAGAHKEC 50
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
60-133 3.20e-07

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 48.59  E-value: 3.20e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGKHF--------VGEKRFESIHDLV-- 127
Cdd:cd10343   6 YHGNITRSKAEELLSkaGKDGSFLVRDSESVSGAYALCVLYQNCVHTYRILPNAEDKlsvqasegVPVRFFTTLPELIef 85
                        90
                ....*....|
gi 4757980  128 ----TDGLIT 133
Cdd:cd10343  86 yqkeNMGLVT 95
C1_aPKC_zeta cd21095
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ...
215-265 3.36e-07

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) zeta type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. Members of this family contain C1 domain found in aPKC isoform zeta. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410448  Cd Length: 55  Bit Score: 46.90  E-value: 3.36e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd21095   3 HLFQAKRFNRRAYCGQCSERIWGLGRQGYKCINCKLLVHKRCHKLVPLTCK 53
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
55-127 4.11e-07

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 48.26  E-value: 4.11e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   55 YYGREFHGIiSREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTL-----NYRLFH--DGKHFVGEK-RFESI 123
Cdd:cd10344   9 YHGWLFEGL-SREKAEELLmlpGNQVGSFLIRESETRRGCYSLSVRHRGSQSrdsvkHYRIFRldNGWFYISPRlTFQCL 87

                ....
gi 4757980  124 HDLV 127
Cdd:cd10344  88 EDMV 91
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
60-127 5.48e-07

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 47.52  E-value: 5.48e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4757980   60 FHGIISREQADELLGGVeGAYILRESQRQPGC---YTLALRFGNQTLNY--RLFHDGKHFVGEKRFESIHDLV 127
Cdd:cd10361   9 YHGLLPREDAEELLKND-GDFLVRKTEPKGGGkrkLVLSVRWDGKIRHFviNRDDGGKYYIEGKSFKSISELI 80
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
60-111 6.15e-07

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198263  Cd Length: 103  Bit Score: 47.53  E-value: 6.15e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 4757980   60 FHGIISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDG 111
Cdd:cd10400   6 YHGKISRETGEKLLLaaGLDGSYLLRDSESVPGVYCLCVLYKGYVYTYRVSQTE 59
C1_aPKC_iota cd21094
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ...
215-264 6.34e-07

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) iota type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain C1 domain found in aPKC isoform iota. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410447  Cd Length: 55  Bit Score: 46.15  E-value: 6.34e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd21094   3 HTFQAKRFNRRAHCAICTDRIWGLGRQGYKCINCKLLVHKKCHKLVTIEC 52
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
60-134 7.29e-07

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 47.39  E-value: 7.29e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRL---------FHDGKHFVGEKRFESIHDLV 127
Cdd:cd09938   4 FYGSITREEAEEYLklaGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIerqlngtyaIAGGKAHCGPAELCEYHSTD 83

                ....*..
gi 4757980  128 TDGLITL 134
Cdd:cd09938  84 LDGLVCL 90
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
46-153 7.74e-07

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 47.70  E-value: 7.74e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   46 PREVENRPKYYGRefhgiISREQADELLGGVE-GAYILRESQRQPGCYTLALRFGNQTLNYRLFH-DGKH-FVGEKRFES 122
Cdd:cd09942   1 PHSLQEAEWYWGD-----ISREEVNEKMRDTPdGTFLVRDASTMKGDYTLTLRKGGNNKLIKIFHrDGKYgFSDPLTFNS 75
                        90       100       110
                ....*....|....*....|....*....|.
gi 4757980  123 IHDlvtdgLITLYIETKAAEYISKMTTNPIY 153
Cdd:cd09942  76 VVE-----LINYYRNNSLAEYNRKLDVKLLY 101
C1_A_C-Raf cd20870
protein kinase C conserved region 1 (C1 domain) found in A- and C-Raf (Rapidly Accelerated ...
214-264 9.37e-07

protein kinase C conserved region 1 (C1 domain) found in A- and C-Raf (Rapidly Accelerated Fibrosarcoma) kinases, and similar proteins; This group includes A-Raf and C-Raf, both of which are serine/threonine-protein kinases. A-Raf, also called proto-oncogene A-Raf or proto-oncogene A-Raf-1, cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. C-Raf, also known as proto-oncogene Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around mid-gestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. Both A- and C-Raf are mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410420  Cd Length: 52  Bit Score: 45.72  E-value: 9.37e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  214 THNFKVHTFRGPHWCEYCANFMWgliaQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20870   3 THNFVRKTFLKLAFCDICQKFLL----NGFRCQTCGYKFHEHCSTKVPTMC 49
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
58-127 1.19e-06

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 46.89  E-value: 1.19e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4757980   58 REFHGIISREQADELL--GGVEGAYILRESQRQPGCYTLALRFGNQTLNY---RLFHDGKHFVGEKRFESIHDLV 127
Cdd:cd09931   1 RWFHGHLSGKEAEKLLleKGKPGSFLVRESQSKPGDFVLSVRTDDDKVTHimiRCQGGKYDVGGGEEFDSLTDLV 75
C1_VAV1 cd20867
protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed ...
215-261 1.29e-06

protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410417  Cd Length: 57  Bit Score: 45.33  E-value: 1.29e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVP 261
Cdd:cd20867   7 HDFQMFSFEETTSCKACQMLLRGTFYQGYRCHRCRAPAHKECLGRVP 53
C1_MRCKbeta cd20865
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
215-264 1.65e-06

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase beta (MRCK beta) and similar proteins; MRCK beta, also called Cdc42-binding protein kinase beta (Cdc42BP-beta), DMPK-like beta, or myotonic dystrophy protein kinase-like beta, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. MRCK beta is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410415  Cd Length: 53  Bit Score: 44.97  E-value: 1.65e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20865   1 HQLSIKSFSSPTQCSHCTSLMVGLVRQGYACEVCSFACHVSCKDSAPQVC 50
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
60-127 2.51e-06

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 45.80  E-value: 2.51e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980   60 FHGIISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFH-DGKHFVGEKRFESIHDLV 127
Cdd:cd10409   4 YYGNVTRHQAECALNerGVEGDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLvDNVYCIGQRRFNSMDELV 74
C1_Myosin-IX cd20818
protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; ...
215-265 2.61e-06

protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains, and a C-terminal tail containing cysteine-rich zinc binding (C1) and Rho-GTPase activating protein (RhoGAP) domains. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis, and IXb is expressed abundantly in tissues of the immune system. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410368  Cd Length: 56  Bit Score: 44.60  E-value: 2.61e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWgLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20818   4 HKFATVQFNIPTYCEVCNSFIW-LMEKGLVCQVCKFTCHKKCYSKITAPCK 53
C1_KSR cd20812
protein kinase C conserved region 1 (C1 domain) found in the kinase suppressor of Ras (KSR) ...
215-264 3.17e-06

protein kinase C conserved region 1 (C1 domain) found in the kinase suppressor of Ras (KSR) family; KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. KSR proteins contain a SAM-like domain, a zinc finger cysteine-rich domain (C1), and a pseudokinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410362  Cd Length: 48  Bit Score: 43.85  E-value: 3.17e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHwCEYCANFMWGliaqGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20812   3 HRFSKKLFMRQT-CDYCHKQMFF----GLKCKDCKYKCHKKCAKKAPPSC 47
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
60-131 3.78e-06

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 45.27  E-value: 3.78e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFH-------DGKHFVGEKR-FESIHDLV- 127
Cdd:cd09933   6 FFGKIKRKDAEKLLlapGNPRGTFLIRESETTPGAYSLSVRDGDDARGDTVKHyrirkldNGGYYITTRAtFPTLQELVq 85

                ....*....
gi 4757980  128 -----TDGL 131
Cdd:cd09933  86 hyskdADGL 94
C1_DGKbeta_rpt1 cd20845
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG ...
214-264 4.27e-06

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG kinase beta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase beta, also called 90 kDa diacylglycerol kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DAG kinase beta contains two copies of the C1 domain. This model corresponds to the first one. DGK-beta contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410395  Cd Length: 66  Bit Score: 44.07  E-value: 4.27e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  214 THNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20845   7 QHVWRLKHFNKPAYCNLCLNMLVGLGKQGLCCSFCKYTVHERCVQRAPASC 57
C1_Stac3 cd20882
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ...
212-260 6.37e-06

protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein 3 (Stac3) and similar proteins; Stac3 is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery. It is required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization. It plays an essential role for normal Ca2+ release from the sarcplasmic reticulum, which ultimately leads to muscle contraction. Stac3 contains a cysteine-rich C1 domain and two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410432  Cd Length: 59  Bit Score: 43.41  E-value: 6.37e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 4757980  212 EKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHV 260
Cdd:cd20882   3 DKPHKFKDHYFKKPKFCDVCARMIVLNNKFGLRCKNCKTNIHHHCQSYV 51
RhoGAP_fRGD2 cd04399
RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
347-468 6.62e-06

RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD2-like proteins. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239864  Cd Length: 212  Bit Score: 46.94  E-value: 6.62e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980  347 IITGALKLYFRDLPIPVITYDTY----SKFID--AAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKK----VTMN 416
Cdd:cd04399  80 TVASVLKLYLLELPDSLIPHDIYdlirSLYSAypPSQEDSDTARIQGLQSTLSQLPKSHIATLDAIITHFYRlieiTKMG 159
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  417 EKDNFMnAENLGIVFGPTLMRPPEDStLTTLHDmRYQKLIVQILIENEDVLF 468
Cdd:cd04399 160 ESEEEY-ADKLATSLSREILRPIIES-LLTIGD-KHGYKFFRDLLTHKDQIF 208
C1_DGK_typeI_rpt1 cd20799
first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; ...
215-264 6.71e-06

first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type I DAG kinases (DGKs) contain EF-hand structures that bind Ca(2+) and recoverin homology domains, in addition to C1 and catalytic domains that are present in all DGKs. Type I DGKs, regulated by calcium binding, include three DGK isozymes (alpha, beta and gamma). DAG kinase alpha, also called 80 kDa DAG kinase, or diglyceride kinase alpha (DGK-alpha), is active upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. DAG kinase beta, also called 90 kDa DAG kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. DGK-alpha contains atypical C1 domains, while DGK-beta and DGK-gamma contain typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410349  Cd Length: 62  Bit Score: 43.51  E-value: 6.71e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20799   6 HVWRLKHFNKPAYCNVCENMLVGLRKQGLCCTFCKYTVHERCVSRAPASC 55
C1_B-Raf cd20871
protein kinase C conserved region 1 (C1 domain) found in B-Raf (Rapidly Accelerated ...
214-264 6.72e-06

protein kinase C conserved region 1 (C1 domain) found in B-Raf (Rapidly Accelerated Fibrosarcoma) kinase and similar proteins; Serine/threonine-protein kinase B-Raf, also called proto-oncogene B-Raf, p94, or v-Raf murine sarcoma viral oncogene homolog B1, activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410421  Cd Length: 60  Bit Score: 43.48  E-value: 6.72e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980  214 THNFKVHTFRGPHWCEYCANFMWgliaQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20871   5 THNFVRKTFFTLAFCDFCRKLLF----QGFRCQTCGYKFHQRCSTEVPLMC 51
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
58-128 8.39e-06

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 44.31  E-value: 8.39e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4757980   58 REFHGIISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGKHF--VGEKRFESIHDLVT 128
Cdd:cd10340   1 RWFHPVISGIEAENLLKtrGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYdlYGGEKFATLSELVQ 75
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
60-127 1.29e-05

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 44.05  E-value: 1.29e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4757980   60 FHGIISREQADELL--GGVEGAYILRESQRQPGCYTLALrFGNQTLN-YRLFHD-GKHFVGEKRFESIHDLV 127
Cdd:cd10353  22 YHGRLDRTIAEERLrqAGKLGSYLIRESDRRPGSFVLSF-LSRTGVNhFRIIAMcGDYYIGGRRFSSLSDLI 92
C1_dGM13116p-like cd20831
protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and ...
215-264 1.32e-05

protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and similar proteins; This group contains uncharacterized proteins including Drosophila melanogaster GM13116p and Caenorhabditis elegans hypothetical protein R11G1.4, both of which contain C2 (a calcium-binding domain) and C1 domains. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410381  Cd Length: 58  Bit Score: 42.71  E-value: 1.32e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4757980  215 HNFKVHTFR-----GPHWCEYCANFMWGLIA-QGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20831   1 HIYNDHTFVathfkGGPSCAVCNKLIPGRFGkQGYQCRDCGLICHKRCHVKVETHC 56
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
60-127 1.91e-05

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 43.34  E-value: 1.91e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4757980   60 FHGIISREQADELL-GGVEGAYILRESQRQPGcYTLALRFGNQTLNYRLFHDGKHF----VGEKRFESIHDLV 127
Cdd:cd10351  10 FHGIISREEAEALLmNATEGSFLVRVSEKIWG-YTLSYRLQSGFKHFLVDASGDFYsflgVDPNRHATLTDLI 81
C1_Stac1 cd20880
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ...
213-257 2.98e-05

protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein (Stac1) and similar proteins; Stac1, also called Src homology 3 and cysteine-rich domain-containing protein, promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity. It plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac1 contains a cysteine-rich C1 domain and two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410430  Cd Length: 57  Bit Score: 41.47  E-value: 2.98e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANFMWGLIAQ-GVRCSDCGLNVHKQCS 257
Cdd:cd20880   1 KAHSFQEYIFKKPTFCDVCNHMIVGTNAKhGLRCKACKMSIHHKCT 46
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
60-107 3.21e-05

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 42.41  E-value: 3.21e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRL 107
Cdd:cd10348   3 LHGALDRNEAVEILkqkADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEI 53
C1_DGK_typeII_rpt1 cd20800
first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; ...
212-264 4.19e-05

first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type II DAG kinases (DGKs) contain pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. Three DGK isozymes (delta, eta and kappa) are classified as type II. DAG kinase delta, also called 130 kDa DAG kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. The DAG kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase kappa is also called diglyceride kinase kappa (DGK-kappa) or 142 kDa DAG kinase. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410350  Cd Length: 60  Bit Score: 41.15  E-value: 4.19e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 4757980  212 EKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20800   2 SGSHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVKAPNNC 54
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
60-133 4.32e-05

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 42.39  E-value: 4.32e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELL--GGVEGAYILRESqRQPGCYTLALrFGNQTLNYRLFH-------DGKHFVGEKR-FESIHDLV-- 127
Cdd:cd09934   9 YVGDMSRQRAESLLkqEDKEGCFVVRNS-STKGLYTVSL-FTKVPGSPHVKHyhikqnaRSEFYLAEKHcFETIPELIny 86
                        90
                ....*....|
gi 4757980  128 ----TDGLIT 133
Cdd:cd09934  87 hqhnSGGLAT 96
C1_TNS1_v cd20888
protein kinase C conserved region 1 (C1 domain) found in tensin-1 (TNS1) variant and similar ...
213-266 4.42e-05

protein kinase C conserved region 1 (C1 domain) found in tensin-1 (TNS1) variant and similar proteins; Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. This model corresponds to the C1 domain found in TNS1 variant. Typical TNS1 does not contain C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410438  Cd Length: 57  Bit Score: 41.01  E-value: 4.42e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 4757980  213 KTHNFKVHTFRGPHWCEYCANfmwGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20888   4 HTHTFKVKTFKKVKSCGICKQ---AITREGSTCRVCKLSCHKKCEAKVATPCVP 54
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
52-127 4.96e-05

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 42.32  E-value: 4.96e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4757980   52 RPKYYGRefhgiISREQADELLG--GVEGAYILRESQRQPGCYTLALRFGNQTLNYRL-FHDGKHFVGEKRFESIHDLV 127
Cdd:cd10408   1 NPWYYGK-----VTRHQAEMALNerGNEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVqLKECVYCIGQRKFSSMEELV 74
C1_DGKgamma_rpt1 cd20846
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase gamma ...
215-261 5.70e-05

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase gamma (DAG kinase gamma) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DGK-gamma contains two copies of the C1 domain. This model corresponds to the first one. DGK-gamma contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410396  Cd Length: 73  Bit Score: 41.07  E-value: 5.70e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQC-SKHVP 261
Cdd:cd20846  17 HAWRLKHFKKPAYCNFCHTMLLGVRKQGLCCSFCKYTVHERCvSKDIA 64
C1_TNS2 cd20887
protein kinase C conserved region 1 (C1 domain) found in tensin-2 and similar proteins; ...
215-266 5.79e-05

protein kinase C conserved region 1 (C1 domain) found in tensin-2 and similar proteins; Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity, and interferes with AKT1 signaling. It contains an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410437  Cd Length: 53  Bit Score: 40.53  E-value: 5.79e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 4757980  215 HNFKVHTFRGPHWCEYCANfmwGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20887   3 HSFKEKTFKKKRACAVCRE---PVGGQGLVCRVCKVASHKKCEAKVTSACQP 51
C1_DEF8 cd20819
protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 ...
215-260 6.33e-05

protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 (DEF-8) and similar proteins; DEF-8 positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. It is involved in bone resorption. DEF-8 contains a protein kinase C conserved region 1 (C1) domain followed by a putative zinc-RING and/or ribbon. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410369  Cd Length: 62  Bit Score: 40.73  E-value: 6.33e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 4757980  215 HNFKVHTFRGP--HWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHV 260
Cdd:cd20819   6 HHFVLQKSKSSskQYCDKCCGIIWGLLQTWYRCTDCGYRCHSKCLNSI 53
C1_RASSF5 cd20886
protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing ...
220-265 6.85e-05

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 5 (RASSF5) and similar proteins; RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. It is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410436  Cd Length: 50  Bit Score: 40.44  E-value: 6.85e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  220 HTFR----GPHWCEYCANFmwgLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20886   4 HRFEpgalGPGWCDLCGRY---ILSQALRCTNCKYTCHSECRDLVQLDCN 50
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
60-127 8.50e-05

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 41.64  E-value: 8.50e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4757980   60 FHGIISREQADELLGGV-EGAYILRESQRQPGCYTLALRFGNQTLNYRL--FHDGKHFVGE--KRFESIHDLV 127
Cdd:cd09945   4 YHGAITRIEAESLLRPCkEGSYLVRNSESTKQDYSLSLKSAKGFMHMRIqrNETGQYILGQfsRPFETIPEMI 76
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
60-138 8.54e-05

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 41.83  E-value: 8.54e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQAD-ELLGGVE--GAYILRESQRQpGCYTLALRFGNQTLNYRLFHD--GKHFVGE-KRFESIHDLV------ 127
Cdd:cd10402  13 YHGSIARDEAErRLYSGAQpdGKFLLRERKES-GTYALSLVYGKTVYHYRIDQDksGKYSIPEgTKFDTLWQLVeylklk 91
                        90
                ....*....|.
gi 4757980  128 TDGLITLYIET 138
Cdd:cd10402  92 PDGLIFVLRES 102
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
60-128 1.19e-04

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 41.94  E-value: 1.19e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4757980   60 FHGIISREQADELLGGvEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGKHF----------VGEKRFESIHDLVT 128
Cdd:cd10337   9 YHGRIPRQVAESLVQR-EGDFLVRDSLSSPGDYVLTCRWKGQPLHFKINRVVLRPseaytrvqyqFEDEQFDSIPALVH 86
SH2_SAP1 cd10342
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked ...
60-122 1.31e-04

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198205  Cd Length: 103  Bit Score: 41.16  E-value: 1.31e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4757980   60 FHGIISREQADELL--GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDgKHfvGEKRFES 122
Cdd:cd10342   6 YHGKISRETGEKLLlaTGLDGSYLLRDSESVPGVYCLCVLYHGYIYTYRVSQT-ET--GSWSAET 67
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
60-127 2.33e-04

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 40.44  E-value: 2.33e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980   60 FHGIISREQADELLGG-VEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK--HFVGEKRFESIHDLV 127
Cdd:cd10406   8 FAGNMERQQTDNLLKShASGTYLIRERPAEAERFAISIKFNDEVKHIKVVEKDNwiHITEAKKFESLLELV 78
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
60-127 2.35e-04

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 40.41  E-value: 2.35e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4757980   60 FHGIISREQADELLgGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLF-HDGKHFVGEKRFESIHDLV 127
Cdd:cd09925  10 YHGKMSRRDAESLL-QTDGDFLVRESTTTPGQYVLTGMQNGQPKHLLLVdPEGVVRTKDRVFESISHLI 77
C1_PDZD8 cd20825
protein kinase C conserved region 1 (C1 domain) found in PDZ domain-containing protein 8 ...
212-258 2.57e-04

protein kinase C conserved region 1 (C1 domain) found in PDZ domain-containing protein 8 (PDZD8) and similar proteins; PDZD8, also called Sarcoma antigen NY-SAR-84/NY-SAR-104, is a molecular tethering protein that connects endoplasmic reticulum (ER) and mitochondrial membranes. PDZD8-dependent ER-mitochondria membrane tethering is essential for ER-mitochondria Ca2+ transfer. In neurons, it is involved in the regulation of dendritic Ca2+ dynamics by regulating mitochondrial Ca2+ uptake. PDZD8 also plays an indirect role in the regulation of cell morphology and cytoskeletal organization. It contains a PDZ domain and a C1 domain. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410375  Cd Length: 55  Bit Score: 38.80  E-value: 2.57e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 4757980  212 EKTHNFKVHTFRGPHWCEYCANFMWglIAQGVRCSDCGLNVHKQCSK 258
Cdd:cd20825   1 EGKHDFVLTQFQNATYCDFCKKKIW--LKEAFQCRLCGMICHKKCLD 45
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
60-131 2.62e-04

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 39.86  E-value: 2.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRL--FHDGKHFVGEKR-FESIHDLV------ 127
Cdd:cd10369   6 FFGAIKRADAEKQLlysENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIrrLDEGGFFLTRRKtFSTLNEFVnyyttt 85

                ....
gi 4757980  128 TDGL 131
Cdd:cd10369  86 SDGL 89
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
60-134 3.07e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 39.49  E-value: 3.07e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4757980   60 FHGIISREQADELLGGV-EGAYILRESqRQPGCY-TLALRFGNQTLNYRLFHDGKHFvgekRFESiHDLVTDGLITL 134
Cdd:cd09923   3 YWGGITRYEAEELLAGKpEGTFLVRDS-SDSRYLfSVSFRTYGRTLHARIEYSNGRF----SFDS-SDPSVPRFPCV 73
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
60-127 3.13e-04

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198274  Cd Length: 97  Bit Score: 39.99  E-value: 3.13e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4757980   60 FHGIISREQADELL--GGVE--GAYILRESQRQPGCYTLALRFGNQTLNYRLF--HDGKHFVGEKRFESIHDLV 127
Cdd:cd10411  11 FHGTLSRVKAAQLVlaGGPRshGLFVIRQSETRPGEYVLTFNFQGKAKHLRLSlnGHGQCHVQHLWFQSVFDML 84
C1_DGKeta_rpt1 cd20848
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG ...
205-265 3.43e-04

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG kinase eta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. The diacylglycerol kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase eta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410398  Cd Length: 86  Bit Score: 39.38  E-value: 3.43e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4757980  205 NDNHFNyeKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20848  22 NVEHFS--GMHNWYACSHARPTFCNVCRESLSGVTSHGLSCEVCKFKAHKRCAVRATNNCK 80
C1_MgcRacGAP cd20821
protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and ...
213-266 3.74e-04

protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and similar proteins; MgcRacGAP, also called Rac GTPase-activating protein 1 (RACGAP1) or protein CYK4, plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling; and ii) after phosphorylation by aurora B, MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain an N-terminal C1 domain, and a C-terminal RhoGAP domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410371  Cd Length: 55  Bit Score: 38.54  E-value: 3.74e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 4757980  213 KTHNFKVHTFRGPHWCEYCA-NFMWGLIAqgVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20821   1 RPHRFVSKTVIKPETCVVCGkRIKFGKKA--LKCKDCRVVCHPDCKDKLPLPCVP 53
C1_GMIP-like cd20816
protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP) ...
213-260 3.80e-04

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410366  Cd Length: 51  Bit Score: 38.39  E-value: 3.80e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 4757980  213 KTHNFKvhTFRGPHWCEYCANFMwglIAQGVRCSDCGLNVHKQCSKHV 260
Cdd:cd20816   1 QTHRFR--RLRTPSKCRECDSYV---YFNGAECEECGLACHKKCLETL 43
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
60-128 4.00e-04

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 39.49  E-value: 4.00e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4757980   60 FHGIISREQADELLGGVE-GAYILRESQRQPGcYTLALRFGNQTLNY--RLFHDGK-HFVGEKR-FESIHDLVT 128
Cdd:cd09946  10 FHGAISREAAENMLESQPlGSFLIRVSHSHVG-YTLSYKAQSSCRHFmvKLLDDGTfMIPGEKVaHTSLHALVT 82
CRIK cd20814
protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) ...
241-264 4.03e-04

protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) and similar proteins; CRIK, also called serine/threonine-protein kinase 21, is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger (C1 domain), and a pleckstrin homology (PH) domain, in addition to other motifs. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410364  Cd Length: 56  Bit Score: 38.38  E-value: 4.03e-04
                        10        20
                ....*....|....*....|....
gi 4757980  241 QGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20814  30 QASKCSECGIVCHPKCSSSLPNTC 53
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
60-138 5.02e-04

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 39.49  E-value: 5.02e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELL---GGVEGAYILREsQRQPGCYTLALRFGNQTLNYRLFHD--GKHFVGE-KRFESIHDLV------ 127
Cdd:cd10401   6 FHGKISREESEQILligSKTNGKFLIRE-RDNNGSYALCLLHDGKVLHYRIDKDktGKLSIPDgKKFDTLWQLVehysyk 84
                        90
                ....*....|.
gi 4757980  128 TDGLITLYIET 138
Cdd:cd10401  85 PDGLLRVLTEP 95
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
60-127 5.05e-04

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 39.53  E-value: 5.05e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLF---HDGKHFV----GEKRFESIHDLV 127
Cdd:cd10414   8 FHHKISRDEAQRLIiqqGLVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIIpveDDGELFHtlddGHTRFTDLIQLV 85
C1_ScPKC1-like_rpt1 cd20822
first protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae ...
215-264 5.32e-04

first protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410372  Cd Length: 52  Bit Score: 37.65  E-value: 5.32e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGliaQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20822   3 HKFVQKQFYQIMRCAVCGEFLVN---AGYQCEDCKYTCHKKCYEKVVTKC 49
C1_TNS3_v cd20889
protein kinase C conserved region 1 (C1 domain) found in tensin-3 (TNS3) variant and similar ...
214-266 5.45e-04

protein kinase C conserved region 1 (C1 domain) found in tensin-3 (TNS3) variant and similar proteins; Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. This model corresponds to the C1 domain found in TNS3 variant. Typical TNS3 does not contain C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410439  Cd Length: 56  Bit Score: 37.95  E-value: 5.45e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 4757980  214 THNFKVHTFRGPHWCEYCANFMWGliaQGVRCSDCGLNVHKQCSKHVPNDCQP 266
Cdd:cd20889   2 SHTFKNKTFKKPKVCSICKQVIDS---QGISCRVCKYACHKKCEAKVVTPCFP 51
C1_p190RhoGEF cd20876
protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange ...
215-261 6.67e-04

protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins; p190RhoGEF, also called Rho guanine nucleotide exchange factor (RGNEF), Rho guanine nucleotide exchange factor 28 (ARHGEF28), or RIP2, is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410426  Cd Length: 61  Bit Score: 37.80  E-value: 6.67e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWGliAQGVRCSDCGLNVHKQCSKHVP 261
Cdd:cd20876   8 HQFVTGSFSGPTLCVVCDKPVTG--KELLQCSNCTVNVHKGCKESAP 52
C1_DGKdelta_rpt1 cd20847
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta ...
201-265 7.01e-04

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410397  Cd Length: 85  Bit Score: 38.54  E-value: 7.01e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4757980  201 ALTHNDNHFNYEKT----------HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQ 265
Cdd:cd20847   1 ALKSVQNREHFESTqysmdhfsgmHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCK 75
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
50-131 7.27e-04

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 38.64  E-value: 7.27e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   50 ENRPKYYGRefhgiISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRL--FHDGKHFVGEKR-FESI 123
Cdd:cd10370   1 EAEPWYFGK-----IKRIEAEKKLllpENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIrqLDEGGFFIARRTtFRTL 75
                        90
                ....*....|....
gi 4757980  124 HDLV------TDGL 131
Cdd:cd10370  76 QELVehyskdSDGL 89
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
60-127 8.74e-04

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 38.74  E-value: 8.74e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLF---HDGKHFV----GEKRFESIHDLV 127
Cdd:cd10413   8 FHGRISREESQRLIgqqGLVDGVFLVRESQRNPQGFVLSLCHLQKVKHYLILpseEEGRLYFsmddGQTRFTDLLQLV 85
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
60-127 2.04e-03

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 37.66  E-value: 2.04e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4757980   60 FHGIISREQADELL-GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFH--DGKHFVGEKR-FESIHDLV 127
Cdd:cd09940   8 FVGEMERDTAENRLeNRPDGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQrsDGLYYLSESRhFKSLVELV 79
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
60-139 2.89e-03

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 37.59  E-value: 2.89e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISR-EQADELLGGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFH--DGKHFVGEKRFESIHDLVTDGLITLYI 136
Cdd:cd10356  13 FHGDISTsESENRLNGKPEGTFLVRFSTSEPGAYTISKVSKNGGISHQRIHrpGGKFQVNNSKYLSVKELIAGEAQALGI 92

                ...
gi 4757980  137 ETK 139
Cdd:cd10356  93 DTP 95
C1_DGKtheta_typeV_rpt2 cd20804
second protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ...
220-264 3.51e-03

second protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410354  Cd Length: 57  Bit Score: 35.74  E-value: 3.51e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  220 HTFRGPH-----WCEYCANFMWGLIAqgVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20804   6 HCWSEPGhskrkFCNVCRKRLEDSPA--FRCEVCEYYVHSDCQDFAVSDC 53
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
60-138 5.74e-03

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 36.42  E-value: 5.74e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4757980   60 FHGIISREQADELL---GGVEGAYILRESQRQPGCYTLALR-----FGNQTLNY---RLFHDGKHFVGEKRFESIHDLV- 127
Cdd:cd10367   6 YFGKIGRKDAERQLlspGNPRGAFLIRESETTKGAYSLSIRdwdqnRGDHVKHYkirKLDTGGYYITTRAQFDTVQELVq 85
                        90
                ....*....|....*.
gi 4757980  128 -----TDGLITLYIET 138
Cdd:cd10367  86 hymevNDGLCYLLTAP 101
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
60-127 6.01e-03

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198273  Cd Length: 97  Bit Score: 36.15  E-value: 6.01e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4757980   60 FHGIISREQADELL--GGV--EGAYILRESQRQPGCYTLALRFGNQTLNYRLF--HDGKHFVGEKRFESIHDLV 127
Cdd:cd10410  11 FHGMLSRLKAAQLVleGGTgsHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSlnEEGQCRVQHLWFQSIFDML 84
C1_Myosin-IXa cd20883
protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar ...
215-264 7.02e-03

protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar proteins; Myosin-IXa, also called unconventional myosin-9a (Myo9a), is a single-headed, actin-dependent motor protein of the unconventional myosin IX class. It is expressed in several tissues and is enriched in the brain and testes. Myosin-IXa contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and a Rho GTPase activating domain (RhoGAP). Myosin-IXa binds the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit, and plays a key role in controlling the molecular structure and function of hippocampal synapses. Moreover, Myosin-IXa functions in epithelial cell morphology and differentiation, such that its knockout mice develop hydrocephalus and kidney dysfunction. Myosin-IXa regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. Myosin-IXa negatively regulates Rho GTPase signaling, and functions as a regulator of kidney tubule function. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410433  Cd Length: 58  Bit Score: 34.94  E-value: 7.02e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4757980  215 HNFKVHTFRGPHWCEYCANFMWgLIAQGVRCSDCGLNVHKQCSKHVPNDC 264
Cdd:cd20883   6 HIFKSTQYSIPTYCEYCSSLIW-MMDRAYVCKLCRYACHKKCCLKTTTKC 54
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
60-127 7.07e-03

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 36.03  E-value: 7.07e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4757980   60 FHGIISREQADEL--LGGVE--GAYILRESQRQPGCYTLALRFGNQTLNYRLF--HDGKHFVGEKRFESIHDLV 127
Cdd:cd10412  11 FHGPISRVKAAQLvqLQGPDahGVFLVRQSETRRGEYVLTFNFQGRAKHLRLSltERGQCRVQHLHFPSVVDML 84
C1_DGKepsilon_typeIII_rpt1 cd20801
first protein kinase C conserved region 1 (C1 domain) found in type III diacylglycerol kinase, ...
213-256 7.53e-03

first protein kinase C conserved region 1 (C1 domain) found in type III diacylglycerol kinase, DAG kinase epsilon, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase epsilon, also called diglyceride kinase epsilon (DGK-epsilon), is the only isoform classified as type III; it possesses a hydrophobic domain in addition to C1 and catalytic domains that are present in all DGKs, and shows selectivity for acyl chains. It is highly selective for arachidonate-containing species of DAG. It may terminate signals transmitted through arachidonoyl-DAG or may contribute to the synthesis of phospholipids with defined fatty acid composition. DAG kinase epsilon contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410351  Cd Length: 54  Bit Score: 34.60  E-value: 7.53e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 4757980  213 KTHNFK-VHTFRGPHWCEYCANfmwgLIAQGVRCSDCGLNVHKQC 256
Cdd:cd20801   2 KGHHWVsTDLFSKPTYCSVCET----LILSGAFCDCCGLCVDEGC 42
 
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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