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 568914439  56 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 135
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 568914439 136 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 165
Cdd:cd13233   81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 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 568914439  56 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 135
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 568914439 136 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 165
Cdd:cd13233   81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 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 568914439   265 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELSEPLFPYSF 344
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439   345 FERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENESGNVAVH 424
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 568914439   425 MVYQNQIAEFMLTEY 439
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439   55 VEKEGYLQKAkiadgGKKLRKNWSTSWIVLSGRKIEFYKDSKqqalpNMKTRHNVESVDLCGAHIEW--AKEKSSRKSVF 132
Cdd:pfam00169   1 VVKEGWLLKK-----GGGKKKSWKKRYFVLFDGSLLYYKDDK-----SGKSKEPKGSISLSGCEVVEvvASDSPKRKFCF 70

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568914439  133 QITTVS---GNEFLLQSDIDFLILDWFQAIKNAI 163
Cdd:pfam00169  71 ELRTGErtgKRTYLLQAESEEERKDWIKAIQSAI 104

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 568914439  56 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 135
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 568914439 136 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 165
Cdd:cd13233   81 TVTGTEFLLQSDNDTEIREWFDAIKAVIQR 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 568914439   265 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELSEPLFPYSF 344
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439   345 FERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENESGNVAVH 424
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 568914439   425 MVYQNQIAEFMLTEY 439
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

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 568914439 267 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQWEDIHVVTGALKMFFRELSEPLFPYSFF 345
Cdd:cd04395   18 VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELY 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 346 ERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENESGNVAV-H 424
Cdd:cd04395   98 PDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMETMVtH 177

                        170
                 ....*....|....*....
gi 568914439 425 MVYQNQIAEFMLTEYDKIF 443
Cdd:cd04395  178 MPDQCKIVETLIQHYDWFF 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 568914439 252 FGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQWEDIHVVTGALKM 330
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 331 FFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPT 410
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 568914439 411 LLRAENESGNVAVH-MVYQNQIAEFMLTEYDKIF 443
Cdd:cd04372  161 LMRPPEDSALTTLNdMRYQILIVQLLITNEDVLF 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 568914439 252 FGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEDIHVVTGALKMF 331
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 332 FRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTL 411
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                 ....*...
gi 568914439 412 LR-AENES 418
Cdd:cd04387  161 LRpSEKES 168

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 568914439 251 IFGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLdVDGIYRVSGNLATIQKLR--FIVNQEEKLNLDDSQwEDIHVVTGAL 328
Cdd:cd04384    2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRheFDSEQIPDLTKDVYI-QDIHSVSSLC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 329 KMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFG 408
Cdd:cd04384   80 KLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                        170       180       190
                 ....*....|....*....|....*....|....
gi 568914439 409 PTLLRAEN-ESG---NVAVHMV--YQNQIAEFML 436
Cdd:cd04384  160 PNLLRSKQiESAcfsGTAAFMEvrIQSVVVEFIL 193

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 568914439 250 QIFGSHLHTVCER--EHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDdsQWEDIHVVTGA 327
Cdd:cd04404    4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFD--QYEDVHLPAVI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 328 LKMFFRELSEPLFPYSFFErFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVF 407
Cdd:cd04404   82 LKTFLRELPEPLLTFDLYD-DIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 568914439 408 GPTLLRAENESGNVAVhMVYQNQIAEFMLTEYDKIF 443
Cdd:cd04404  161 GPNLLWAKDASMSLSA-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 568914439 250 QIFGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVN-QEEKLNLDDsQWEDIHVVTGAL 328
Cdd:cd04386    3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDaGTFSLPLDE-FYSDPHAVASAL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 329 KMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFG 408
Cdd:cd04386   82 KSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 568914439 409 PTLLRAENESGNVAVHM---VYQNQIAEFMLTEYDKIFSSE 446
Cdd:cd04386  162 PNLLWAKNEGSLAEMAAgtsVHVVAIVELIISHADWFFPGE 202

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 568914439 267 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRfivnqeEKL-----NLDDSQwEDIHVVTGALKMFFRELSEPLFP 341
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktVPNLSK-VDIHVICGCLKDFLRSLKEPLIT 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 342 YSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKiVAKASQNLMSTQSLGIVFGPTL 411
Cdd:cd04382   90 FALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQR-VAQSPECKMDINNLARVFGPTI 158

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. 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 568914439 252 FGSHLHTVCEREHST--VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKL-NLDDSQWEDIHVVTGAL 328
Cdd:cd04379    1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 329 KMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIET---MRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGI 405
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNthlTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                        170
                 ....*....|....
gi 568914439 406 VFGPTLLRAENESG 419
Cdd:cd04379  161 CFGPVLMFCSQEFS 174

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 568914439 263 EHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQwedIHVVTGALKMFFRELSEPLFP 341
Cdd:cd04407   11 NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADpENVKLENYP---IHAITGLLKQWLRELPEPLMT 87

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568914439 342 YSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENES 418
Cdd:cd04407   88 FAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDSS 164

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud 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 568914439 251 IFGSHLHTVCEREH-----STVPWFVKQCIEAVEK-RGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNL-DDSQWEDIHV 323
Cdd:cd04400    1 IFGSPLEEAVELSShkyngRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLfSSSLYPDVHT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 324 VTGALKMFFRELSEPLFPYSFFERFVEAIKKQDSN-EKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQS 402
Cdd:cd04400   81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRsQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 568914439 403 LGIVFGPTLlraenesgNVAVHMvyqnqIAEFmLTEYDKIF 443
Cdd:cd04400  161 VCIVFSPTL--------NIPAGI-----FVLF-LTDFDCIF 187

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 568914439 267 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQweDIHVVTGALKMFFRELSEPLFPYSFFE 346
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPRELYT 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 347 RFVEAiKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKA-----------SQNLMSTQSLGIVFGPTLLR-- 413
Cdd:cd04376   87 AFIGT-ALLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAadsidedgqevSGNKMTSLNLATIFGPNLLHkq 165

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 568914439 414 --AENESGNVAVHM---VYQNQIAEFMLTEYDKIF 443
Cdd:cd04376  166 ksGEREFVQASLRIeesTAIINVVQTMIDNYEELF 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 568914439 237 SLKTLQEKGLIKDQifgshlhtvcerehstVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLddS 316
Cdd:cd04393    6 PLQELQQAGQPENG----------------VPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDL--S 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 317 QWEDIHVVTGALKMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIET-MRSLVKRLPPPNHDTMKILFRHLTKIVAKASQ 395
Cdd:cd04393   68 KEADVCSAASLLRLFLQELPEGLIPASLQIRLMQLYQDYNGEDEFGRkLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHE 147

                        170
                 ....*....|....
gi 568914439 396 NLMSTQSLGIVFGP 409
Cdd:cd04393  148 NRMTAENLAAVFGP 161

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 568914439 252 FGSHLHTVCEREHStVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSqweDIHVVTGALKM 330
Cdd:cd04406    1 FGVELSRLTSEDRS-VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDaNSVNLDDY---NIHVIASVFKQ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914439 331 FFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPT 410
Cdd:cd04406   77 WLRDLPNPLMTFELYEEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPC 156

                 ...
gi 568914439 411 LLR 413
Cdd:cd04406  157 ILR 159