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 15080081 192 EKSGLLNMTKIAQGGRKLRKNWGPSWVVLTGNSLVFYREPPPTApsaGWGPAGSRPESSVDLRGAALAHGRHLSSRRNVL 271
Cdd:cd13233   1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAA---KSGNPYSKPESSVDLRGASIEWAKEKSSRKNVF 77

                        90       100       110
                ....*....|....*....|....*....|...
gi 15080081 272 HIRTIPGHEFLLQSDHETELRAWHRALRTVIER 304
Cdd:cd13233  78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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 15080081 192 EKSGLLNMTKIAQGGRKLRKNWGPSWVVLTGNSLVFYREPPPTApsaGWGPAGSRPESSVDLRGAALAHGRHLSSRRNVL 271
Cdd:cd13233   1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAA---KSGNPYSKPESSVDLRGASIEWAKEKSSRKNVF 77

                        90       100       110
                ....*....|....*....|....*....|...
gi 15080081 272 HIRTIPGHEFLLQSDHETELRAWHRALRTVIER 304
Cdd:cd13233  78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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 15080081    402 DTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDREravtsdgryvfpeqpgqeGRLDLDSTEWDdIHVVTG 481
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSG------------------PDPDLDLSEYD-VHDVAG 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081    482 ALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIAHSDKNRMTPHNLGIV 561
Cdd:smart00324  62 LLKLFLRELPEPLITYELYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIV 141

                          170       180       190
                   ....*....|....*....|....*....|..
gi 15080081    562 FGPTLFRPEQETSDPAAHALYPGQLVQLMLTN 593
Cdd:smart00324 142 FGPTLLRPPDGEVASLKDIRHQNTVIEFLIEN 173

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081    191 VEKSGLLNMTkiaqgGRKLRKNWGPSWVVLTGNSLVFYREPPptapsagwGPAGSRPESSVDLRGA--ALAHGRHLSSRR 268
Cdd:smart00233   1 VIKEGWLYKK-----SGGGKKSWKKRYFVLFNSTLLYYKSKK--------DKKSYKPKGSIDLSGCtvREAPDPDSSKKP 67

                           90       100       110
                   ....*....|....*....|....*....|....
gi 15080081    269 NVLHIRTIPGHEFLLQSDHETELRAWHRALRTVI 302
Cdd:smart00233  68 HCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101

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 15080081 192 EKSGLLNMTKIAQGGRKLRKNWGPSWVVLTGNSLVFYREPPPTApsaGWGPAGSRPESSVDLRGAALAHGRHLSSRRNVL 271
Cdd:cd13233   1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAA---KSGNPYSKPESSVDLRGASIEWAKEKSSRKNVF 77

                        90       100       110
                ....*....|....*....|....*....|...
gi 15080081 272 HIRTIPGHEFLLQSDHETELRAWHRALRTVIER 304
Cdd:cd13233  78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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 15080081    402 DTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDREravtsdgryvfpeqpgqeGRLDLDSTEWDdIHVVTG 481
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSG------------------PDPDLDLSEYD-VHDVAG 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081    482 ALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIAHSDKNRMTPHNLGIV 561
Cdd:smart00324  62 LLKLFLRELPEPLITYELYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIV 141

                          170       180       190
                   ....*....|....*....|....*....|..
gi 15080081    562 FGPTLFRPEQETSDPAAHALYPGQLVQLMLTN 593
Cdd:smart00324 142 FGPTLLRPPDGEVASLKDIRHQNTVIEFLIEN 173

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 15080081 389 FGCQLESLCQREGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDRERAVTsdgryvfpeqpgqegrLDL 468
Cdd:cd04398   1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNV----------------LLI 64

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 469 DSTEWD-DIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIAH 547
Cdd:cd04398  65 SPEDYEsDIHSVASLLKLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEH 144

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15080081 548 SDKNRMTPHNLGIVFGPTLFrpeQETSDPAAHALYPGQLVQLMLTNFTSLF 598
Cdd:cd04398 145 ESVNRMSVNNLAIIWGPTLM---NAAPDNAADMSFQSRVIETLLDNAYQIF 192

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 15080081 388 VFGCQLESlCQ--REGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgryvfpeqpgQEGR 465
Cdd:cd04395   1 TFGVPLDD-CPpsSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNR-----------------GGFD 62

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 466 LDLDSTEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVI 545
Cdd:cd04395  63 IDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVA 142

                       170       180
                ....*....|....*....|....*...
gi 15080081 546 AHSDKNRMTPHNLGIVFGPTLFRPEQET 573
Cdd:cd04395 143 DNSEVNKMEPRNLAIVFGPTLVRTSDDN 170

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 15080081 406 SFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKL-RFLVDRERAvtsdgryvfpeqpgQEGRLDLDSTEWDdIHVVTGALK 484
Cdd:cd04374  30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLlSLGLDPKTS--------------TPGDVDLDNSEWE-IKTITSALK 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 485 LFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIAHSDKNRMTPHNLGIVFGP 564
Cdd:cd04374  95 TYLRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGP 174

                ....*....
gi 15080081 565 TLFRPEQET 573
Cdd:cd04374 175 TLLRPQEET 183

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 15080081 388 VFGCQLESLCQREGDTVPSFLRLCIAAVDKRGLdVDGIYRVSGNLAVVQKLRFLVDRERAVTsdgryvFPEQPGQEgrld 467
Cdd:cd04384   2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPD------LTKDVYIQ---- 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 468 ldstewdDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIAH 547
Cdd:cd04384  71 -------DIHSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKY 143

                       170       180
                ....*....|....*....|....
gi 15080081 548 SDKNRMTPHNLGIVFGPTLFRPEQ 571
Cdd:cd04384 144 CSITNMHAKNLAIVWAPNLLRSKQ 167

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 15080081 387 QVFGCQLESLCQREGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDrerAVTSDgryvfpeqpgqegrL 466
Cdd:cd04386   3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALD---AGTFS--------------L 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 467 DLDStEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIA 546
Cdd:cd04386  66 PLDE-FYSDPHAVASALKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQ 144

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15080081 547 HSDKNRMTPHNLGIVFGPTLFRPEQETS---DPAAHALYPGQLVQLMLTNFTSLFP 599
Cdd:cd04386 145 KSDENKMSPSNIAIVLAPNLLWAKNEGSlaeMAAGTSVHVVAIVELIISHADWFFP 200

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 15080081 389 FGCQLESLCQrEGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgryvfpeqpgqegrlDL 468
Cdd:cd04377   1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDT----------------------DP 57

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 469 DSTEWDD--IHVVTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRVIA 546
Cdd:cd04377  58 DSVNLEDypIHVITSVLKQWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVAL 137

                       170       180       190
                ....*....|....*....|....*....|
gi 15080081 547 HSDKNRMTPHNLGIVFGPTLFRpEQETSDP 576
Cdd:cd04377 138 QEEVNRMSANALAIVFAPCILR-CPDTADP 166

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 15080081 389 FGCQLESLCQREGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRflvdreravtsdgryvfpeQPGQEGRLDL 468
Cdd:cd04408   1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLC-------------------QAFENGRDLV 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 469 DSTEwDDIHVVTGALKLFLRELPQPLVPPLLLPHF----RAALALSE--------SEQCLSQIQELIGSMPKPNHDTLRY 536
Cdd:cd04408  62 DLSG-HSPHDITSVLKHFLKELPEPVLPFQLYDDFialaKELQRDSEkaaespsiVENIIRSLKELLGRLPVSNYNTLRH 140

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15080081 537 LLEHLCRVIAHSDKNRMTPHNLGIVFGPTLFRPeQETSDPAAHAL----YPGQLVQLMLTN 593
Cdd:cd04408 141 LMAHLYRVAERFEDNKMSPNNLGIVFGPTLLRP-LVGGDVSMICLldtgYQAQLVEFLISN 200

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 15080081 389 FGCQLESLCQREGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRflvdreravtsdgryvfpeQPGQEGRLDL 468
Cdd:cd04409   1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLC-------------------QAFENGKDLV 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 469 DSTEWDDiHVVTGALKLFLRELPQPLVPPLLLPHF-------------RAALALSESEQ---------CLSQIQELIGSM 526
Cdd:cd04409  62 ELSELSP-HDISNVLKLYLRQLPEPLILFRLYNEFiglakesqhvnetQEAKKNSDKKWpnmctelnrILLKSKDLLRQL 140

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 527 PKPNHDTLRYLLEHLCRVIAHSDKNRMTPHNLGIVFGPTLFRPEQETSDPAAHAL--YPGQ--LVQLMLT 592
Cdd:cd04409 141 PAPNYNTLQFLIVHLHRVSEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLvdYPHQarLVELLIT 210

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 15080081 404 VPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLR--FLvdRERAVtsdgryvfpeqpgqegrLDLDSTewdDIHVVTG 481
Cdd:cd04382  17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKekFL--RGKTV-----------------PNLSKV---DIHVICG 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 482 ALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEHLCRViAHSDKNRMTPHNLGIV 561
Cdd:cd04382  75 CLKDFLRSLKEPLITFALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARV 153

                ....*.
gi 15080081 562 FGPTLF 567
Cdd:cd04382 154 FGPTIV 159

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 15080081 388 VFGCQLESLCQR-----EGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGnlaVVQKLRFLvdRERAvtsdgryvfpeqpgq 462
Cdd:cd04391   1 LFGVPLSTLLERdqkkvPGSKVPLIFQKLINKLEERGLETEGILRIPG---SAQRVKFL--CQEL--------------- 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 463 EGRLDLDSTEWDDIHV--VTGALKLFLRELPQPLVPPLLLPHFRAALALSESEQCLSQIQELIGSMPKPNHDTLRYLLEH 540
Cdd:cd04391  61 EAKFYEGTFLWDQVKQhdAASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEF 140

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15080081 541 LCRVIAHSDKNRMTPHNLGIVFGPTLFRP----------EQETSDPAAHAlypGQLVQLMLTN 593
Cdd:cd04391 141 LQKVVDHEEKNKMNLWNVAMIMAPNLFPPrgkhskdnesLQEEVNMAAGC---ANIMRLLIRY 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 15080081 387 QVFGCQLESLcQREG---DTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFlvdreravtsdgRYvfpeqpgqE 463
Cdd:cd04393   1 KVFGVPLQEL-QQAGqpeNGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQ------------RL--------D 59

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 464 GRLDLDSTEWDDIHVVTGALKLFLRELPQPLVPPLLLPHFRAALA--LSESEQClSQIQELIGSMPKPNHDTLRYLLEHL 541
Cdd:cd04393  60 SGEEVDLSKEADVCSAASLLRLFLQELPEGLIPASLQIRLMQLYQdyNGEDEFG-RKLRDLLQQLPPVNYSLLKFLCHFL 138

                       170       180
                ....*....|....*....|....*.
gi 15080081 542 CRVIAHSDKNRMTPHNLGIVFGPTLF 567
Cdd:cd04393 139 SNVASQHHENRMTAENLAAVFGPDVF 164

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 15080081 404 VPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDReravtsdgryvfpeqpGQEGRLDLDSTewddIHVVTGAL 483
Cdd:cd04376   9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR----------------GIDVVLDENHS----VHDVAALL 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15080081 484 KLFLRELPQPLVPPLLLPHFRAALALSESEQcLSQIQELIGSMPKPNHDTLRYLLEHLCRVIAHSDK-----------NR 552
Cdd:cd04376  69 KEFFRDMPDPLLPRELYTAFIGTALLEPDEQ-LEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNK 147

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 15080081 553 MTPHNLGIVFGPTLFRPEQ-------ETSDPAAHALYPGQLVQLMLTNFTSLF 598
Cdd:cd04376 148 MTSLNLATIFGPNLLHKQKsgerefvQASLRIEESTAIINVVQTMIDNYEELF 200

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 15080081 389 FGCQLESLCQR----EGDTVPSFLRLCIAAVDKRGLDVDGIYRVSGNLAVVQKLRFLVDREravtsdgryvfpEQPGQEg 464
Cdd:cd04381   1 FGASLSLAVERsrchDGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRR------------ESPNLE- 67