Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319   1 MTKIAQGGRKLRKSWGPAWVVLTGNSLVFYRERPPqcapSQGWAPAGSRPESSVDLRGAALASGRQLSSRRNVLHIRTVP 80
Cdd:cd13233     8 KTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKS----AAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQISTVT 83

                          90       100
                  ....*....|....*....|....*..
gi 1958790319  81 GHEFLLQSDEETELRAWHRALRAVIER 107
Cdd:cd13233    84 GTEFLLQSDNDTEIREWFDAIKAVIQR 110

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 215 PSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDRERAVTSDgrymfpeqpgqegkldldsAEWDDIHVITGALK 294
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLD-------------------LEEEDVHVVASLLK 61

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 295 LFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAHSDKNRMTAHNLGIVFGP 374
Cdd:pfam00620  62 LFLRELPEPLLTFELYEEFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGP 141

                  ....*..
gi 1958790319 375 TLFRPEQ 381
Cdd:pfam00620 142 TLLRPPD 148

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319   1 MTKIAQGGRKLRKSWGPAWVVLTGNSLVFYRERPPqcapSQGWAPAGSRPESSVDLRGAALASGRQLSSRRNVLHIRTVP 80
Cdd:cd13233     8 KTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKS----AAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQISTVT 83

                          90       100
                  ....*....|....*....|....*..
gi 1958790319  81 GHEFLLQSDEETELRAWHRALRAVIER 107
Cdd:cd13233    84 GTEFLLQSDNDTEIREWFDAIKAVIQR 110

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319   8 GRKLRKSWGPAWVVLTGNSLVFYRERPpqcapsqgwAPAGSRPESSVDLRGAALASGRQLSS--RRNVLHIRTV---PGH 82
Cdd:pfam00169  11 GGGKKKSWKKRYFVLFDGSLLYYKDDK---------SGKSKEPKGSISLSGCEVVEVVASDSpkRKFCFELRTGertGKR 81

                          90       100
                  ....*....|....*....|....
gi 1958790319  83 EFLLQSDEETELRAWHRALRAVIE 106
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSAIR 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 215 PSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDRERAVTSDgrymfpeqpgqegkldldsAEWDDIHVITGALK 294
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLD-------------------LEEEDVHVVASLLK 61

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 295 LFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAHSDKNRMTAHNLGIVFGP 374
Cdd:pfam00620  62 LFLRELPEPLLTFELYEEFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGP 141

                  ....*..
gi 1958790319 375 TLFRPEQ 381
Cdd:pfam00620 142 TLLRPPD 148

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 1958790319 215 PSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDRERavtsdgrymfpeqpgqegklDLDSAEWDDIHVITGALK 294
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--------------------DIDDLEDYDVHDVASLLK 60

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 295 LFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAHSDKNRMTAHNLGIVFGP 374
Cdd:cd00159    61 LYLRELPEPLIPFELYDEFIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAP 140

                         170       180
                  ....*....|....*....|....*....
gi 1958790319 375 TLFRPEQEASDMAAHVVYPGQLIQLMLNN 403
Cdd:cd00159   141 TLLRPPDSDDELLEDIKKLNEIVEFLIEN 169

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 198 VFGCQLESlCQ--REGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgrymfpeqpgQEGK 275
Cdd:cd04395     1 TFGVPLDD-CPpsSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNR-----------------GGFD 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 276 LDLDSAEWDDIHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVI 355
Cdd:cd04395    63 IDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVA 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958790319 356 AHSDKNRMTAHNLGIVFGPTLFRPEQEA-SDMAAHVVYPGQLIQLMLNNFASLF 408
Cdd:cd04395   143 DNSEVNKMEPRNLAIVFGPTLVRTSDDNmETMVTHMPDQCKIVETLIQHYDWFF 196

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 199 FGCQLESLCQREGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDReravtsDGRymfpeqpgqegKLDL 278
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDR------DGE-----------KADI 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 279 DSAEWDDIHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAHS 358
Cdd:cd04372    64 SATVYPDINVITGALKLYFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHE 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958790319 359 DKNRMTAHNLGIVFGPTLFR-PEQEASDMAAHVVYPGQLIQLMLNNFASLF 408
Cdd:cd04372   144 KDNKMNAENLGIVFGPTLMRpPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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 1958790319 199 FGCQLESLCQREGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVD-RERAVTSDGRYMfpeqpgqegkld 277
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDtNNKDVSVMLSEM------------ 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 278 ldsaewdDIHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAH 357
Cdd:cd04387    69 -------DVNAIAGTLKLYFRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAER 141

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1958790319 358 SDKNRMTAHNLGIVFGPTLFRPEQEASDMAAHVVYPGQLIQLM 400
Cdd:cd04387   142 EEVNKMSLHNLATVFGPTLLRPSEKESKIPTNTMTDSWSLEVM 184

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 1958790319 198 VFGCQLESLCQREGDTVPSFVRLCVEAVDKKGLdVDGIYRVSGNLAVVQKLRFLVDRERAvtsdgrymfPEQPGQEGKld 277
Cdd:cd04384     2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQI---------PDLTKDVYI-- 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 278 ldsaewDDIHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAH 357
Cdd:cd04384    70 ------QDIHSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKY 143

                         170       180
                  ....*....|....*....|....
gi 1958790319 358 SDKNRMTAHNLGIVFGPTLFRPEQ 381
Cdd:cd04384   144 CSITNMHAKNLAIVWAPNLLRSKQ 167

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 197 QVFGCQLESLCQR--EGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgrymfpeqpgqeg 274
Cdd:cd04404     4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNM-------------------- 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 275 KLDLDSAEWDDIHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHcLSKIQKLIDSLPRPNHDTLQYILEHLCRV 354
Cdd:cd04404    64 GEPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDLYDDIVGFLNVDKEER-VERVKQLLQTLPEENYQVLKYLIKFLVQV 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958790319 355 IAHSDKNRMTAHNLGIVFGPTLFRPEQEASDMAAhVVYPGQLIQLMLNNFASLF 408
Cdd:cd04404   143 SAHSDQNKMTNSNLAVVFGPNLLWAKDASMSLSA-INPINTFTKFLLDHQDEIF 195

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 1958790319 197 QVFGCQLESLCQREGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDreravtsdgrymfpeqpGQEGKL 276
Cdd:cd04386     3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALD-----------------AGTFSL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 277 DLDSaEWDDIHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIA 356
Cdd:cd04386    66 PLDE-FYSDPHAVASALKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQ 144

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958790319 357 HSDKNRMTAHNLGIVFGPTLFRPEQEASD------MAAHVVypgQLIQLMLNNFASLF 408
Cdd:cd04386   145 KSDENKMSPSNIAIVLAPNLLWAKNEGSLaemaagTSVHVV---AIVELIISHADWFF 199

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 1958790319 199 FGCQLESLCQrEGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgrymfpeqpgqegklDL 278
Cdd:cd04377     1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDT----------------------DP 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 279 DSAEWDD--IHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIA 356
Cdd:cd04377    58 DSVNLEDypIHVITSVLKQWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVAL 137

                         170       180
                  ....*....|....*....|..
gi 1958790319 357 HSDKNRMTAHNLGIVFGPTLFR 378
Cdd:cd04377   138 QEEVNRMSANALAIVFAPCILR 159

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 1958790319 214 VPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLR--FLvdRERAVTSDGRYmfpeqpgqegkldldsaewdDIHVITG 291
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKekFL--RGKTVPNLSKV--------------------DIHVICG 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 292 ALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRViAHSDKNRMTAHNLGIV 371
Cdd:cd04382    75 CLKDFLRSLKEPLITFALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARV 153

                  ....*.
gi 1958790319 372 FGPTLF 377
Cdd:cd04382   154 FGPTIV 159

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 1958790319 199 FGCQLESLCQREGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRflvdreravtsdgrymfpeQPGQEGKLDL 278
Cdd:cd04408     1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLC-------------------QAFENGRDLV 61

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 279 DSAEwDDIHVITGALKLFFRELPQPLVPALLLPHF----RDALELSE--------PEHCLSKIQKLIDSLPRPNHDTLQY 346
Cdd:cd04408    62 DLSG-HSPHDITSVLKHFLKELPEPVLPFQLYDDFialaKELQRDSEkaaespsiVENIIRSLKELLGRLPVSNYNTLRH 140

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958790319 347 ILEHLCRVIAHSDKNRMTAHNLGIVFGPTLFRPeQEASDMAAHVV----YPGQLIQLMLNN 403
Cdd:cd04408   141 LMAHLYRVAERFEDNKMSPNNLGIVFGPTLLRP-LVGGDVSMICLldtgYQAQLVEFLISN 200

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 197 QVFGCQLESLcQREG---DTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFlvdreravtsdgRYmfpeqpgqE 273
Cdd:cd04393     1 KVFGVPLQEL-QQAGqpeNGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQ------------RL--------D 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 274 GKLDLDSAEWDDIHVITGALKLFFRELPQPLVPALLLPHF-RDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLC 352
Cdd:cd04393    60 SGEEVDLSKEADVCSAASLLRLFLQELPEGLIPASLQIRLmQLYQDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLS 139

                         170       180
                  ....*....|....*....|....*
gi 1958790319 353 RVIAHSDKNRMTAHNLGIVFGPTLF 377
Cdd:cd04393   140 NVASQHHENRMTAENLAAVFGPDVF 164

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 1958790319 198 VFGCQLESLCQREGD----TVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDreravtsdgrymfpeqPGQE 273
Cdd:cd04390     2 VFGQRLEDTVAYERKfgprLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFD----------------AGER 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 274 GKLDLDSaewdDIHVITGALKLFFRELPQPLVPALLLPHFRDA--LELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHL 351
Cdd:cd04390    66 PSFDSDT----DVHTVASLLKLYLRELPEPVIPWAQYEDFLSCaqLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFL 141

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958790319 352 CRVIAHSDKNRMTAHNLGIVFGPTLFRPEQE-ASDMAAHVVYPGQLIQLMLNNFASLF 408
Cdd:cd04390   142 DEVQSNSSVNKMSVQNLATVFGPNILRPKVEdPATIMEGTPQIQQLMTVMISKHEPLF 199

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 1958790319 214 VPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgrymfpeqpGQEGKLDldsaEWDDIHVITGAL 293
Cdd:cd04376     9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR----------------GIDVVLD----ENHSVHDVAALL 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 294 KLFFRELPQPLVPALLLPHFRDALELsEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRVIAHSDK-----------NR 362
Cdd:cd04376    69 KEFFRDMPDPLLPRELYTAFIGTALL-EPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNK 147

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958790319 363 MTAHNLGIVFGPTLFRPEQ-------EASDMAAHVVYPGQLIQLMLNNFASLFT 409
Cdd:cd04376   148 MTSLNLATIFGPNLLHKQKsgerefvQASLRIEESTAIINVVQTMIDNYEELFM 201

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 1958790319 199 FGCQLESLCQR----EGDTVPSFVRLCVEAVDKKGLDVDGIYRVSGNLAVVQKLRFLVDREravtsdgrymfpEQPGQEg 274
Cdd:cd04381     1 FGASLSLAVERsrchDGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRR------------ESPNLE- 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790319 275 klDLDSaewddiHVITGALKLFFRELPQPLVPALLLPHFRDALELSEPEHCLSKIQKLIDSLPRPNHDTLQYILEHLCRV 354
Cdd:cd04381    68 --EYEP------PTVASLLKQYLRELPEPLLTKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHV 139