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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852   32 GRRVVTFSCCRMP--PSHELDHQRLLEYLKYTL-DQYVENDYTIVYFHYGLNSRNKPSLGWLQSAYKEFDRKYKKNLKAL 108
Cdd:pfam13716   1 GRPVLVFISKLLPsrPASLDDLDRLLFYLLKTLsEKLKGKPFVVVVDHTGVTSENFPSLSFLKKAYDLLPRAFKKNLKAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 311213852  109 YVVHPTSFIK-VLWNILKPLISHKFGKKVIYFNYLSELHEHLKYDQLVIP-PEVLRYDE 165
Cdd:pfam13716  81 YVVHPSTFLRtFLKTLGSLLGSKKLRKKVHYVSSLSELWEGIDREQLPTElPGVLSYDE 139

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852   32 GRRVVTFSCCRMP--PSHELDHQRLLEYLKYTL-DQYVENDYTIVYFHYGLNSRNKPSLGWLQSAYKEFDRKYKKNLKAL 108
Cdd:pfam13716   1 GRPVLVFISKLLPsrPASLDDLDRLLFYLLKTLsEKLKGKPFVVVVDHTGVTSENFPSLSFLKKAYDLLPRAFKKNLKAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 311213852  109 YVVHPTSFIK-VLWNILKPLISHKFGKKVIYFNYLSELHEHLKYDQLVIP-PEVLRYDE 165
Cdd:pfam13716  81 YVVHPSTFLRtFLKTLGSLLGSKKLRKKVHYVSSLSELWEGIDREQLPTElPGVLSYDE 139

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852    16 DVARHGILQVAGDDRFGRRVVTFSCCRMPPsHELDHQRLLEYLKYTLDQYVEN---DYTIVYFHYGLNSRNKPS----LG 88
Cdd:smart00516   3 ELLKAYIPGGRGYDKDGRPVLIERAGRFDL-KSVTLEELLRYLVYVLEKILQEekkTGGIEGFTVIFDLKGLSMsnpdLS 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 311213852    89 WLQSAYKEFDRKYKKNLKALYVVHPTSFIKVLWNILKPLISHKFGKKV--IYFNYLSELHEHLKYDQLviPPEVLRYDE 165
Cdd:smart00516  82 VLRKILKILQDHYPERLGKVYIINPPWFFRVLWKIIKPFLDEKTREKIrfVGNDSKEELLEYIDKEQL--PEELGGTLD 158

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 311213852   209 IPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKPVNFDDYG-DIHIPAVILKTFLRELPQPLLTFQAYEQ 287
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEyDVHDVAGLLKLFLRELPEPLITYELYEE 82

                   ..
gi 311213852   288 IL 289
Cdd:smart00324  83 FI 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852   32 GRRVVTFSCCRMP--PSHELDHQRLLEYLKYTL-DQYVENDYTIVYFHYGLNSRNKPSLGWLQSAYKEFDRKYKKNLKAL 108
Cdd:pfam13716   1 GRPVLVFISKLLPsrPASLDDLDRLLFYLLKTLsEKLKGKPFVVVVDHTGVTSENFPSLSFLKKAYDLLPRAFKKNLKAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 311213852  109 YVVHPTSFIK-VLWNILKPLISHKFGKKVIYFNYLSELHEHLKYDQLVIP-PEVLRYDE 165
Cdd:pfam13716  81 YVVHPSTFLRtFLKTLGSLLGSKKLRKKVHYVSSLSELWEGIDREQLPTElPGVLSYDE 139

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852    16 DVARHGILQVAGDDRFGRRVVTFSCCRMPPsHELDHQRLLEYLKYTLDQYVEN---DYTIVYFHYGLNSRNKPS----LG 88
Cdd:smart00516   3 ELLKAYIPGGRGYDKDGRPVLIERAGRFDL-KSVTLEELLRYLVYVLEKILQEekkTGGIEGFTVIFDLKGLSMsnpdLS 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 311213852    89 WLQSAYKEFDRKYKKNLKALYVVHPTSFIKVLWNILKPLISHKFGKKV--IYFNYLSELHEHLKYDQLviPPEVLRYDE 165
Cdd:smart00516  82 VLRKILKILQDHYPERLGKVYIINPPWFFRVLWKIIKPFLDEKTREKIrfVGNDSKEELLEYIDKEQL--PEELGGTLD 158

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 311213852 210 PPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKPVNFDDYGDIHIPAVILKTFLRELPQPLLTFQAYEQIL 289
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

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 311213852 193 FGVSLQYLKDKNQGelIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREI-QRLYNQGKPVNFDDYGdIHIPAVILKTF 271
Cdd:cd04377    1 FGVSLSSLTSEDRS--VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELrQGLDTDPDSVNLEDYP-IHVITSVLKQW 77

                         90       100       110
                 ....*....|....*....|....*....|.
gi 311213852 272 LRELPQPLLTFQAYEQILGITCVP--GEHLQ 300
Cdd:cd04377   78 LRELPEPLMTFELYENFLRAMELEekQERVR 108

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 191 QQFGVSLQ-YLKdkNQGELIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQG--KPVNFDDYGDIHIPAVI 267
Cdd:cd04386    3 PVFGTPLEeHLK--RTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGtfSLPLDEFYSDPHAVASA 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 311213852 268 LKTFLRELPQPLLTFQAYEQILGITCVPGE 297
Cdd:cd04386   81 LKSYLRELPDPLLTYNLYEDWVQAANKPDE 110

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNQGelIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREI-QRLYNQGKPVNFDDYgDIHIPAVILKTF 271
Cdd:cd04406    1 FGVELSRLTSEDRS--VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELrQGLDTDANSVNLDDY-NIHVIASVFKQW 77

                         90
                 ....*....|....*...
gi 311213852 272 LRELPQPLLTFQAYEQIL 289
Cdd:cd04406   78 LRDLPNPLMTFELYEEFL 95

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNQ---GELIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKPVNFDDYgDIHIPAVILK 269
Cdd:cd04381    1 FGASLSLAVERSRchdGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLEEY-EPPTVASLLK 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 311213852 270 TFLRELPQPLLT---FQAYEQILGITCVpGEHLQQNEQL 305
Cdd:cd04381   80 QYLRELPEPLLTkelMPRFEEACGRPTE-AEREQELQRL 117

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNQ----GELIPPVLRFTVTYLREKGLRTEGLFRRSASVQTV----REIQRLYNQGKpvnFD-DYGDIHI 263
Cdd:cd04391    2 FGVPLSTLLERDQkkvpGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVkflcQELEAKFYEGT---FLwDQVKQHD 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 311213852 264 PAVILKTFLRELPQPLLT---FQAYEQILGI 291
Cdd:cd04391   79 AASLLKLFIRELPQPLLTveyLPAFYSVQGL 109

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNQGEL----------IPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQgKPVNFDDYGD-- 260
Cdd:cd04397    1 FGVPLEILVEKFGADStlgvgpgklrIPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDK-NPTEVPDLSKen 79

                         90       100
                 ....*....|....*....|....*..
gi 311213852 261 -IHIpAVILKTFLRELPQPLLTFQAYE 286
Cdd:cd04397   80 pVQL-AALLKKFLRELPDPLLTFKLYR 105

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 209 IPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKPVNFDDYGDIHIPAVILKTFLRELPQPLLTFQAYEQI 288
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                 ..
gi 311213852 289 LG 290
Cdd:cd04376   89 IG 90

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 311213852 222 EKGLRTEGLFRRSASVQTVREIQRLYNQGKPVNFDDYG-DIHIPAVILKTFLRELPQPLLT---FQAYEQI 288
Cdd:cd04392   21 EKNLRVEGLFRKPGNSARQQELRDLLNSGTDLDLESGGfHAHDCATVLKGFLGELPEPLLThahYPAHLQI 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKnQGELIPPV-LRFTVTYLREK-----GLRTEGLFRRSASVQTVREIQRLYNQGKpVNFDDYGDIHIPAV 266
Cdd:cd04389    1 FGSSLEEIMDR-QKEKYPELkLPWILTFLSEKvlalgGFQTEGIFRVPGDIDEVNELKLRVDQWD-YPLSGLEDPHVPAS 78

                         90       100
                 ....*....|....*....|...
gi 311213852 267 ILKTFLRELPQPLLTFQAYEQIL 289
Cdd:cd04389   79 LLKLWLRELEEPLIPDALYQQCI 101

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNQGELIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKPVnfDDYGDIHIPAV--ILKT 270
Cdd:cd04382    1 IGTGELADFDPSTSPMIPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTV--PNLSKVDIHVIcgCLKD 78

                         90
                 ....*....|..
gi 311213852 271 FLRELPQPLLTF 282
Cdd:cd04382   79 FLRSLKEPLITF 90

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 194 GVSLQYLKDKNQgeLIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGK-PVNFDDYG-DIHIPAVILKTF 271
Cdd:cd04383    5 GSLEEYIQDSGQ--AIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEdPLADDQNDhDINSVAGVLKLY 82

                         90       100       110
                 ....*....|....*....|....*....|
gi 311213852 272 LRELPQPLLTFQAYEQIlgITCVPGEHLQQ 301
Cdd:cd04383   83 FRGLENPLFPKERFEDL--MSCVKLENPTE 110

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNqGELIPPVLRFTVTYLREKGLRTEGLFRRS---ASVQTVREIQRLYNqgKPVNFDDYgDIHIPAVILK 269
Cdd:cd04375    5 FGVPLLVNLQRT-GQPLPRSIQQAMRWLRNNALDQVGLFRKSgvkSRIQKLRSMIESST--DNVNYDGQ-QAYDVADMLK 80

                         90       100
                 ....*....|....*....|..
gi 311213852 270 TFLRELPQPLLTFQAYEQILGI 291
Cdd:cd04375   81 QYFRDLPEPLLTNKLSETFIAI 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 204 NQGELIPPVLRFTVTYLREKGLrTEGLFRRSASVQTVREIQRLYNQGKP---VNFDDYGDIHIPAVILKTFLRELPQPLL 280
Cdd:cd04384   13 NSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIpdlTKDVYIQDIHSVSSLCKLYFRELPNPLL 91

                 ....*..
gi 311213852 281 TFQAYEQ 287
Cdd:cd04384   92 TYQLYEK 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKdKNQGElIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKPVNFDDYG-DIHIPAVILKTF 271
Cdd:cd04373    1 FGVPLANVV-TSEKP-IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSKDfTVNAVAGALKSF 78

                         90       100
                 ....*....|....*....|....
gi 311213852 272 LRELPQPLLTF---QAYEQILGIT 292
Cdd:cd04373   79 FSELPDPLIPYsmhLELVEAAKIN 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKDKNQGELIPPVLRFTVTyLREKGLRTEGLFRRSAS-VQTVREIQRLYNQGKPVNFDDYGDIHIPAViLKTF 271
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAE-IENRALGVQGIYRISGSkARVEKLCQAFENGRDLVDLSGHSPHDITSV-LKHF 78

                         90       100
                 ....*....|....*....|
gi 311213852 272 LRELPQPLLTFQAYEQILGI 291
Cdd:cd04408   79 LKELPEPVLPFQLYDDFIAL 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 193 FGVSLQYLKdKNQGELIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNqgkpVNFDDYG------DIHIPAV 266
Cdd:cd04387    1 FGVKISTVT-KRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFD----TNNKDVSvmlsemDVNAIAG 75

                         90
                 ....*....|....*....
gi 311213852 267 ILKTFLRELPQPLLTFQAY 285
Cdd:cd04387   76 TLKLYFRELPEPLFTDELY 94

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311213852 203 KNQGELIPPVLRFTVTYLREKGLRTEGLFRRSASVQTVREIQRLYNQGKP-VNFDDYGDIHIPAViLKTFLRELPQPLLT 281
Cdd:cd04409   10 KKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDlVELSELSPHDISNV-LKLYLRQLPEPLIL 88

                         90
                 ....*....|
gi 311213852 282 FQAYEQILGI 291
Cdd:cd04409   89 FRLYNEFIGL 98