RhoGAP_BRCC3-like: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of BRCC3-like proteins. This subgroup also contains two groups of closely related proteins, BRCC3 and DEPDC7, which both contain a C-terminal RhoGAP-like domain and an N-terminal DEP (Disheveled, Egl-10, and Pleckstrin) domain. The function(s) of BRCC3 and DEPDC7 are 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 182 ISQEDVEDVWRYVTMIYLQTILGVPSIEELINPNQVIPQYIMYNM------ANTSKHGVVILQNKSeDLPHWVLSAMKCL 255
Cdd:cd04405    1 LSPEVVEEIWKEQTLIRLLQLVGLPLLEELLDPALVNPKHISYNMdpdvytSNYLDREVVKLFSKS-QLDHWLLSAMDCL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 256 ANWPRC--NDTNSLTYV------GFERDVFKTIADYFLDLPEPLLTFEYYELFVNILGLLQPHLERVAINALQLCCLLLP 327
Cdd:cd04405   80 ANWPDQlvVDVSRPLYSqhdmlsGFKRLLFKTIAKYYGQLKEPLLTFHLFDIFVGILELLGNGKEEVALEALQLCLLLLP 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 328 PPNRRKLQLLMRMISRMSQNvDLPKLHEEIGTRSLMINTFSRCVLCCAeevDLDELLASRLVSFLMDHHQEILQVPTYLQ 407
Cdd:cd04405  160 PASRRELRRLLRFMARAAKN-DMPRLHKEIENRMLVKQTFSRAILCSK---DLDEGLADLLVLFLMDHHQDIFKVPGSLH 235

RhoGAP_BRCC3-like: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of BRCC3-like proteins. This subgroup also contains two groups of closely related proteins, BRCC3 and DEPDC7, which both contain a C-terminal RhoGAP-like domain and an N-terminal DEP (Disheveled, Egl-10, and Pleckstrin) domain. The function(s) of BRCC3 and DEPDC7 are 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 182 ISQEDVEDVWRYVTMIYLQTILGVPSIEELINPNQVIPQYIMYNM------ANTSKHGVVILQNKSeDLPHWVLSAMKCL 255
Cdd:cd04405    1 LSPEVVEEIWKEQTLIRLLQLVGLPLLEELLDPALVNPKHISYNMdpdvytSNYLDREVVKLFSKS-QLDHWLLSAMDCL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 256 ANWPRC--NDTNSLTYV------GFERDVFKTIADYFLDLPEPLLTFEYYELFVNILGLLQPHLERVAINALQLCCLLLP 327
Cdd:cd04405   80 ANWPDQlvVDVSRPLYSqhdmlsGFKRLLFKTIAKYYGQLKEPLLTFHLFDIFVGILELLGNGKEEVALEALQLCLLLLP 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 328 PPNRRKLQLLMRMISRMSQNvDLPKLHEEIGTRSLMINTFSRCVLCCAeevDLDELLASRLVSFLMDHHQEILQVPTYLQ 407
Cdd:cd04405  160 PASRRELRRLLRFMARAAKN-DMPRLHKEIENRMLVKQTFSRAILCSK---DLDEGLADLLVLFLMDHHQDIFKVPGSLH 235

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408   27 GMPLRKHRQHLKKYSNCFTAVEAVDWLYDLlrsnsnfGPEVTRQQTIQLLRKFLKNHVIEDIKGRWGseNLDDNNQLFRF 106
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDN-------LEIITREEAVELGQLLLDQGLIHHVGDKHG--LFKDSYYFYRF 71

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408  253 KCLANWPRCNDTNSLTyvgferDVFKtiaDYFLDLPEPLLTFEYYELFVNILGLlqpHLERVAINALQLCCLLLPPPNRR 332
Cdd:pfam00620  42 PDVDLDLEEEDVHVVA------SLLK---LFLRELPEPLLTFELYEEFIEAAKL---PDEEERLEALRELLRKLPPANRD 109

                          90       100
                  ....*....|....*....|
gi 564339408  333 KLQLLMRMISRMSQNVDLPK 352
Cdd:pfam00620 110 TLRYLLAHLNRVAQNSDVNK 129

RhoGAP_BRCC3-like: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of BRCC3-like proteins. This subgroup also contains two groups of closely related proteins, BRCC3 and DEPDC7, which both contain a C-terminal RhoGAP-like domain and an N-terminal DEP (Disheveled, Egl-10, and Pleckstrin) domain. The function(s) of BRCC3 and DEPDC7 are 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 182 ISQEDVEDVWRYVTMIYLQTILGVPSIEELINPNQVIPQYIMYNM------ANTSKHGVVILQNKSeDLPHWVLSAMKCL 255
Cdd:cd04405    1 LSPEVVEEIWKEQTLIRLLQLVGLPLLEELLDPALVNPKHISYNMdpdvytSNYLDREVVKLFSKS-QLDHWLLSAMDCL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 256 ANWPRC--NDTNSLTYV------GFERDVFKTIADYFLDLPEPLLTFEYYELFVNILGLLQPHLERVAINALQLCCLLLP 327
Cdd:cd04405   80 ANWPDQlvVDVSRPLYSqhdmlsGFKRLLFKTIAKYYGQLKEPLLTFHLFDIFVGILELLGNGKEEVALEALQLCLLLLP 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 328 PPNRRKLQLLMRMISRMSQNvDLPKLHEEIGTRSLMINTFSRCVLCCAeevDLDELLASRLVSFLMDHHQEILQVPTYLQ 407
Cdd:cd04405  160 PASRRELRRLLRFMARAAKN-DMPRLHKEIENRMLVKQTFSRAILCSK---DLDEGLADLLVLFLMDHHQDIFKVPGSLH 235

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408   27 GMPLRKHRQHLKKYSNCFTAVEAVDWLYDLlrsnsnfGPEVTRQQTIQLLRKFLKNHVIEDIKGRWGseNLDDNNQLFRF 106
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDN-------LEIITREEAVELGQLLLDQGLIHHVGDKHG--LFKDSYYFYRF 71

DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408  24 FRVGMPLRKHRQHLKKYSNCFTAVEAVDWLYDllrsnsnFGPEVTRQQTIQLLRKFLKNHVIEDIKGrwGSENLDDNNQL 103
Cdd:cd04371    9 SDSGVPIKDRKYHLKTYPNCFTGSELVDWLLD-------NLEAITREEAVELGQALLKHGLIHHVSD--DKHTFRDSYAL 79

                 ..
gi 564339408 104 FR 105
Cdd:cd04371   80 YR 81

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGEF (GDP/GTP exchange factor) PIKfyve-like proteins. PIKfyve contains N-terminal Fyve finger and DEP domains, a central chaperonin-like domain and a C-terminal PIPK (phosphatidylinositol phosphate kinase) domain. PIKfyve-like proteins are important phosphatidylinositol (3)-monophosphate (PtdIns(3)P)-5-kinases, producing PtdIns(3,5)P2, which plays a major role in multivesicular body (MVB) sorting and control of retrograde traffic from the vacuole back to the endosome and/or Golgi. PIKfyve itself has been shown to be play a role in regulating early-endosome-to-trans-Golgi network (TGN) retrograde trafficking.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 564339408  16 LWNEVTTSfRVGMPLRKHRQHLKKYSNCFTAVEAVDWL 53
Cdd:cd04448    2 LWEKICRS-STGIEFQDHRYRLRTYTNCILGKELVNWL 38

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 275 DVFKTIADYFLDLPEPLLTFEYYELFVNILGLLQPHlerVAINALQLCCLLLPPPNRRKLQLLMRMISRMSQNVDLPKLh 354
Cdd:cd00159   54 DVASLLKLYLRELPEPLIPFELYDEFIELAKIEDEE---ERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKM- 129

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564339408 355 eeiGTRSLMInTFSRCVLCCAEEVD---LDELLASRLVSFLMDH 395
Cdd:cd00159  130 ---TASNLAI-VFAPTLLRPPDSDDellEDIKKLNEIVEFLIEN 169

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408   263 DTNSLTyvgferDVFKTiadYFLDLPEPLLTFEYYELFVNILgLLQPHLERvaINALQLCCLLLPPPNRRKLQLLMRMIS 342
Cdd:smart00324  55 DVHDVA------GLLKL---FLRELPEPLITYELYEEFIEAA-KLEDETER--LRALRELLSLLPPANRATLRYLLAHLN 122

                   ....*..
gi 564339408   343 RMSQNVD 349
Cdd:smart00324 123 RVAEHSE 129

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408 283 YFLDLPEPLLTFEYYELFVNILGLLQPHlERVAinALQLCCLLLPPPNRRKLQLLMRMISRMSqnvdlpkLHEEI---GT 359
Cdd:cd04377   77 WLRELPEPLMTFELYENFLRAMELEEKQ-ERVR--ALYSVLEQLPRANLNTLERLIFHLVRVA-------LQEEVnrmSA 146

                         90       100
                 ....*....|....*....|
gi 564339408 360 RSLMInTFSRCVLCCAEEVD 379
Cdd:cd04377  147 NALAI-VFAPCILRCPDTAD 165

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by cyclic AMP, a second messenger that plays a role in the control of diverse cellular processes, such as cell adhesion and insulin secretion. Epac-like proteins share a common domain architecture, containing RasGEF, DEP and CAP-effector (cAMP binding) domains. The DEP domain is involved in membrane localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564339408  29 PLRKHRQHLKKYSNCFTAVEAVDWLYDLlrsnsnfGPEV-TRQQTIQLLRKFLKNHVIEDIKGRWgseNLDDNNQLFRFP 107
Cdd:cd04437   16 LIRDRKYHLRTYRQCCVGTELVDWLLQQ-------SPCVqSRSQAVGMWQVLLEEGVLLHVDQEL---HFQDKYQFYRFS 85