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 71990631 276 PIFGLELTDLYMRTGKKVPVIVEKCCASIEDQGIVTGIYRQCGIQSNIQRLRAKFDSGAEPDLHEF-GQRDIYSVSSLLK 354
Cdd:cd04384   1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDvYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 355 QYFRQLPNPLFTYQAYPKLIEAFEKeDSLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWS 434
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSA-ASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 71990631 435 PNLFRPPPTLN----GADTHLLSGLNVHTAICDFFI 466
Cdd:cd04384 160 PNLLRSKQIESacfsGTAAFMEVRIQSVVVEFILNH 195

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71990631 168 AAVVTKDFEPTESSQLRLRVGDIVSITEMstASPSEQTFWKAKltisnqkivdpqnarLGFEIGYFPRDCV 238
Cdd:cd11835   1 AAHVIKRYTAQAPDELSLEVGDIVSVIDM--PPPEESTWWRGK---------------KGFQVGFFPSECV 54

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 71990631 276 PIFGLELTDLYMRTGKKVPVIVEKCCASIEDQGIVTGIYRQCGIQSNIQRLRAKFDSGAEPDLHEF-GQRDIYSVSSLLK 354
Cdd:cd04384   1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDvYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 355 QYFRQLPNPLFTYQAYPKLIEAFEKeDSLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWS 434
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSA-ASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 71990631 435 PNLFRPPPTLN----GADTHLLSGLNVHTAICDFFI 466
Cdd:cd04384 160 PNLLRSKQIESacfsGTAAFMEVRIQSVVVEFILNH 195

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631   294 PVIVEKCCASIEDQGI-VTGIYRQCGIQSNIQRLRAKFDSGAEPDLhEFGQRDIYSVSSLLKQYFRQLPNPLFTYQAYPK 372
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLdTEGIFRVSGSASRIKELREAFDRGPDVDL-DLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631   373 LIEAFEKEDSlSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPNLFRPPP 442
Cdd:pfam00620  80 FIEAAKLPDE-EERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71990631 168 AAVVTKDFEPTESSQLRLRVGDIVSITEMstASPSEQTFWKAKltisnqkivdpqnarLGFEIGYFPRDCV 238
Cdd:cd11835   1 AAHVIKRYTAQAPDELSLEVGDIVSVIDM--PPPEESTWWRGK---------------KGFQVGFFPSECV 54

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 71990631 276 PIFGLELTDLYMRTGKKVPVIVEKCCASIEDQGIVTGIYRQCGIQSNIQRLRAKFDSGAEPDLHEF-GQRDIYSVSSLLK 354
Cdd:cd04384   1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDvYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 355 QYFRQLPNPLFTYQAYPKLIEAFEKeDSLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWS 434
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSA-ASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 71990631 435 PNLFRPPPTLN----GADTHLLSGLNVHTAICDFFI 466
Cdd:cd04384 160 PNLLRSKQIESacfsGTAAFMEVRIQSVVVEFILNH 195

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631   294 PVIVEKCCASIEDQGI-VTGIYRQCGIQSNIQRLRAKFDSGAEPDLhEFGQRDIYSVSSLLKQYFRQLPNPLFTYQAYPK 372
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLdTEGIFRVSGSASRIKELREAFDRGPDVDL-DLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631   373 LIEAFEKEDSlSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPNLFRPPP 442
Cdd:pfam00620  80 FIEAAKLPDE-EERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 278 FGLELTDLYMRTGKKVPVIVEKCCASIEDQGI-VTGIYRQCGIQSNIQRLRAKFDSGAEPDLH---EFGQRDIYSVSSLL 353
Cdd:cd04398   1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLnLEGIYRLSGNVSRVNKLKELFDKDPLNVLLispEDYESDIHSVASLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 354 KQYFRQLPNPLFTYQAYPKLIEAFEKEDSLSEKvESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVW 433
Cdd:cd04398  81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRR-DALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIW 159

                       170
                ....*....|
gi 71990631 434 SPNLFRPPPT 443
Cdd:cd04398 160 GPTLMNAAPD 169

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 289 TGKKVPVIVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRAKFDSGA------EPDLHEfgqrdiYSVSSLLKQYFRQLP 361
Cdd:cd04385  11 TDNDIPVIVDKCIDFITQHGLMSeGIYRKNGKNSSVKKLLEAFRKDArsvqlrEGEYTV------HDVADVLKRFLRDLP 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 362 NPLFTYQAYPKLIEAFEKEDSlSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPNLFRPP 441
Cdd:cd04385  85 DPLLTSELHAEWIEAAELENK-DERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTD 163

                ....*....
gi 71990631 442 PTLNGADTH 450
Cdd:cd04385 164 EHSVGQTSH 172

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 278 FGLELTDLYMRTGKKVPVIVEKCCASIEDQGI-VTGIYRQCGIQSNIQRLRAKFDSGAEPDLHEFGQRDIYSVSSLLKQY 356
Cdd:cd04403   1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLdVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 357 FRQLPNPLFTYQAYPKLIEAFEKEDSlSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPN 436
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKLSDY-EQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPT 159

                ....
gi 71990631 437 LFRP 440
Cdd:cd04403 160 LLRP 163

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 278 FGLELTDLYMRTGKKVPVIVEKCCASIEDQG-IVTGIYRQCGIQSNIQRLRAKFDSGAE-PDLHEFGQRDIysvSSLLKQ 355
Cdd:cd04378   1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRAlGVQGIYRVSGSKARVEKLCQAFENGKDlVELSELSPHDI---SSVLKL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 356 YFRQLPNPLFTYQAYPKLIeAFEKE-DSLSEK-------------VESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSL 421
Cdd:cd04378  78 FLRQLPEPLILFRLYNDFI-ALAKEiQRDTEEdkapntpievnriIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEE 156

                       170       180
                ....*....|....*....|..
gi 71990631 422 TDMTSKNLAIVWSPNLFRPPPT 443
Cdd:cd04378 157 NKMSPNNLGIVFGPTLIRPRPG 178

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 71990631 278 FGLELTDLyMRTGKKVPVIVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRAKFDSGAEPDLHEFgQRDIYSVSSLLKQY 356
Cdd:cd04373   1 FGVPLANV-VTSEKPIPIFLEKCVEFIEATGLETeGIYRVSGNKTHLDSLQKQFDQDHNLDLVSK-DFTVNAVAGALKSF 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 357 FRQLPNPLFTYQAYPKLIEAFEKEDsLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPN 436
Cdd:cd04373  79 FSELPDPLIPYSMHLELVEAAKIND-REQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPT 157

                       170       180       190
                ....*....|....*....|....*....|..
gi 71990631 437 LFRPPPTLNGAdthlLSGLNVHTAICDFFIEN 468
Cdd:cd04373 158 LMRPDFTSMEA----LSATRIYQTIIETFIQQ 185

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 71990631 278 FGLELTDLyMRTGKKVPVIVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRAKFDSGAEP-DLHEFGqrdIYSVSSLLKQ 355
Cdd:cd04377   1 FGVSLSSL-TSEDRSVPLVLEKLLEHIEMHGLYTeGIYRKSGSANKIKELRQGLDTDPDSvNLEDYP---IHVITSVLKQ 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 356 YFRQLPNPLFTYQAYPKLIEAFEKEDSlSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSP 435
Cdd:cd04377  77 WLRELPEPLMTFELYENFLRAMELEEK-QERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAP 155

                ....*...
gi 71990631 436 NLFRPPPT 443
Cdd:cd04377 156 CILRCPDT 163

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 71990631 278 FGLELTDLYMRTGKKVPVIVEKCCASIEDQGI-VTGIYRQCGIQSNIQRLRAKFDSGAEP-DLHEFGQRDIysvSSLLKQ 355
Cdd:cd04408   1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALgVQGIYRISGSKARVEKLCQAFENGRDLvDLSGHSPHDI---TSVLKH 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 356 YFRQLPNPLFTYQAYPKLI-----------EAFEKEDSLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDM 424
Cdd:cd04408  78 FLKELPEPVLPFQLYDDFIalakelqrdseKAAESPSIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKM 157

                       170
                ....*....|....*...
gi 71990631 425 TSKNLAIVWSPNLFRPPP 442
Cdd:cd04408 158 SPNNLGIVFGPTLLRPLV 175

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 296 IVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRA-----KFDSGAEPDLHEfGQRDIYSVSSLLKQYFRQLPNPLFTYQA 369
Cdd:cd04374  31 FVRKCIEAVETRGINEqGLYRVVGVNSKVQKLLSlgldpKTSTPGDVDLDN-SEWEIKTITSALKTYLRNLPEPLMTYEL 109

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71990631 370 YPKLIEAfEKEDSLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPNLFRP 440
Cdd:cd04374 110 HNDFINA-AKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRP 179

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 278 FGLELTDLymrTGKK--VPVIVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRAKFDSGaePDLHEFGQRDIYSVSSLLK 354
Cdd:cd04407   1 FGVRVGSL---TSNKtsVPIVLEKLLEHVEMHGLYTeGIYRKSGSANRMKELHQLLQAD--PENVKLENYPIHAITGLLK 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 355 QYFRQLPNPLFTYQAYPKLIEAFEkedsLSEKVESLRF---SLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAI 431
Cdd:cd04407  76 QWLRELPEPLMTFAQYNDFLRAVE----LPEKQEQLQAiyrVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAI 151

                       170
                ....*....|..
gi 71990631 432 VWSPNLFRPPPT 443
Cdd:cd04407 152 VFAPCLLRCPDS 163

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 277 IFG--LELTDLYMRT--GKKVPVIVEKCCASIEDQGIV-TGIYRQCGIQSNIQRLRAKFDSGAEPDLHefGQRDIYSVSS 351
Cdd:cd04390   2 VFGqrLEDTVAYERKfgPRLVPILVEQCVDFIREHGLKeEGLFRLPGQANLVKQLQDAFDAGERPSFD--SDTDVHTVAS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 352 LLKQYFRQLPNPLFTYQAYPKLIEAFEKEDSLSEK-VESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLA 430
Cdd:cd04390  80 LLKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKgLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLA 159

                       170
                ....*....|
gi 71990631 431 IVWSPNLFRP 440
Cdd:cd04390 160 TVFGPNILRP 169

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 71990631 278 FGLELTDLyMRTGKKVPVIVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRAKFDSGAepDLHEFGQRDIYSVSSLLKQY 356
Cdd:cd04406   1 FGVELSRL-TSEDRSVPLVVEKLINYIEMHGLYTeGIYRKSGSTNKIKELRQGLDTDA--NSVNLDDYNIHVIASVFKQW 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 357 FRQLPNPLFTYQAYPKLIEAFEKEDSlSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSPN 436
Cdd:cd04406  78 LRDLPNPLMTFELYEEFLRAMGLQER-RETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPC 156

                ....*..
gi 71990631 437 LFRPPPT 443
Cdd:cd04406 157 ILRCPDT 163

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 71990631 277 IFGLELTDLYMRTGKKVPVIVEKCCASIEDQGIV-TGIYRQCGIQSNIQRLRAKFDSGAEPDLHEFGQRDIYSVSSLLKQ 355
Cdd:cd04383   2 LFNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQhQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 356 YFRQLPNPLFTYQAYPKLIEAFeKEDSLSEKVESLRFSLETMPEAHYRTAKFLMEHLTRLCKSKSLTDMTSKNLAIVWSP 435
Cdd:cd04383  82 YFRGLENPLFPKERFEDLMSCV-KLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGP 160

                ....*.
gi 71990631 436 NLFRPP 441
Cdd:cd04383 161 TLMPVP 166

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 71990631 277 IFGLELTDLYMRT-----GKKVPVIVEKCCASIEDQGIVT-GIYRQCGIQSNIQRLRAKFDSGAEPDLHEFGQRDIYSVS 350
Cdd:cd04391   1 LFGVPLSTLLERDqkkvpGSKVPLIFQKLINKLEERGLETeGILRIPGSAQRVKFLCQELEAKFYEGTFLWDQVKQHDAA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71990631 351 SLLKQYFRQLPNPLFTYQaypkLIEAFEKEDSLSEKVESLR-FSLETM--PEAHYRTAKFLMEHLTRLCKSKSLTDMTSK 427
Cdd:cd04391  81 SLLKLFIRELPQPLLTVE----YLPAFYSVQGLPSKKDQLQaLNLLVLllPEANRDTLKALLEFLQKVVDHEEKNKMNLW 156

                       170
                ....*....|...
gi 71990631 428 NLAIVWSPNLFRP 440
Cdd:cd04391 157 NVAMIMAPNLFPP 169