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 1395777151  44 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 123
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1395777151 124 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 153
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 1395777151  44 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 123
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1395777151 124 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 153
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 1395777151  253 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELSEPLFPYSF 332
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151  333 FERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENESGNVAVH 412
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 1395777151  413 MVYQNQIAEFMLTEY 427
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151  43 VEKEGYLQKAkiadgGKKLRKNWSTSWIVLSGRKIEFYKDSKqqalpNMKTRHNVESVDLCGAHIEW--AKEKSSRKSVF 120
Cdd:pfam00169   1 VVKEGWLLKK-----GGGKKKSWKKRYFVLFDGSLLYYKDDK-----SGKSKEPKGSISLSGCEVVEvvASDSPKRKFCF 70

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1395777151 121 QITTVS---GNEFLLQSDIDFLILDWFQAIKNAI 151
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 1395777151  44 EKEGYLQKAKIADGGKKLRKNWSTSWIVLSGRKIEFYKDSKQQALPNMKTRHNVESVDLCGAHIEWAKEKSSRKSVFQIT 123
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQIS 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1395777151 124 TVSGNEFLLQSDIDFLILDWFQAIKNAIDR 153
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 1395777151  253 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELSEPLFPYSF 332
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151  333 FERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENESGNVAVH 412
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 1395777151  413 MVYQNQIAEFMLTEY 427
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 1395777151 255 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQWEDIHVVTGALKMFFRELSEPLFPYSFF 333
Cdd:cd04395    18 VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELY 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 334 ERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENESGNVAV-H 412
Cdd:cd04395    98 PDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMETMVtH 177

                         170
                  ....*....|....*....
gi 1395777151 413 MVYQNQIAEFMLTEYDKIF 431
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 1395777151 240 FGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQWEDIHVVTGALKM 318
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 319 FFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPT 398
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1395777151 399 LLRAENESGNVAVH-MVYQNQIAEFMLTEYDKIF 431
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 1395777151 240 FGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLR--FIVNQEEKLNLDDSQweDIHVVTGALK 317
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKaaFDTNNKDVSVMLSEM--DVNAIAGTLK 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 318 MFFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGP 397
Cdd:cd04387    79 LYFRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGP 158

                         170
                  ....*....|
gi 1395777151 398 TLLR-AENES 406
Cdd:cd04387   159 TLLRpSEKES 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 1395777151 239 IFGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLdVDGIYRVSGNLATIQKLR--FIVNQEEKLNLDDSQwEDIHVVTGAL 316
Cdd:cd04384     2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRheFDSEQIPDLTKDVYI-QDIHSVSSLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 317 KMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFG 396
Cdd:cd04384    80 KLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1395777151 397 PTLLRAEN-ESG---NVAVHMV--YQNQIAEFML 424
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 1395777151 238 QIFGSHLHTVCER--EHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDdsQWEDIHVVTGA 315
Cdd:cd04404     4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFD--QYEDVHLPAVI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 316 LKMFFRELSEPLFPYSFFErFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVF 395
Cdd:cd04404    82 LKTFLRELPEPLLTFDLYD-DIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1395777151 396 GPTLLRAENESGNVAVhMVYQNQIAEFMLTEYDKIF 431
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 1395777151 238 QIFGSHLHTVCEREHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVN-QEEKLNLDDsQWEDIHVVTGAL 316
Cdd:cd04386     3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDaGTFSLPLDE-FYSDPHAVASAL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 317 KMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFG 396
Cdd:cd04386    82 KSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1395777151 397 PTLLRAENESGNVAVHM---VYQNQIAEFMLTEYDKIFSSE 434
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 1395777151 255 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRfivnqeEKL-----NLDDSQwEDIHVVTGALKMFFRELSEPLFP 329
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktVPNLSK-VDIHVICGCLKDFLRSLKEPLIT 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 330 YSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKiVAKASQNLMSTQSLGIVFGPTL 399
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 1395777151 240 FGSHLHTVCEREHST--VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKL-NLDDSQWEDIHVVTGAL 316
Cdd:cd04379     1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 317 KMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIET---MRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGI 393
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNthlTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                         170
                  ....*....|....
gi 1395777151 394 VFGPTLLRAENESG 407
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 1395777151 251 EHSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSQwedIHVVTGALKMFFRELSEPLFP 329
Cdd:cd04407    11 NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADpENVKLENYP---IHAITGLLKQWLRELPEPLMT 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1395777151 330 YSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPTLLRAENES 406
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 1395777151 239 IFGSHLHTVCEREH-----STVPWFVKQCIEAVEK-RGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNL-DDSQWEDIHV 311
Cdd:cd04400     1 IFGSPLEEAVELSShkyngRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLfSSSLYPDVHT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 312 VTGALKMFFRELSEPLFPYSFFERFVEAIKKQDSN-EKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQS 390
Cdd:cd04400    81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRsQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1395777151 391 LGIVFGPTLlraenesgNVAVHMvyqnqIAEFmLTEYDKIF 431
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 1395777151 255 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQweDIHVVTGALKMFFRELSEPLFPYSFFE 334
Cdd:cd04376     9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPRELYT 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 335 RFVEAiKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKA-----------SQNLMSTQSLGIVFGPTLLR-- 401
Cdd:cd04376    87 AFIGT-ALLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAadsidedgqevSGNKMTSLNLATIFGPNLLHkq 165

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1395777151 402 --AENESGNVAVHM---VYQNQIAEFMLTEYDKIF 431
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 1395777151 225 SLKTLQEKGLIKDQifgshlhtvcerehstVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLddS 304
Cdd:cd04393     6 PLQELQQAGQPENG----------------VPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDL--S 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 305 QWEDIHVVTGALKMFFRELSEPLFPYSFFERFVEAIKKQDSNEKIET-MRSLVKRLPPPNHDTMKILFRHLTKIVAKASQ 383
Cdd:cd04393    68 KEADVCSAASLLRLFLQELPEGLIPASLQIRLMQLYQDYNGEDEFGRkLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHE 147

                         170
                  ....*....|....
gi 1395777151 384 NLMSTQSLGIVFGP 397
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 1395777151 240 FGSHLHTVCEREHStVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQE-EKLNLDDSqweDIHVVTGALKM 318
Cdd:cd04406     1 FGVELSRLTSEDRS-VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDaNSVNLDDY---NIHVIASVFKQ 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1395777151 319 FFRELSEPLFPYSFFERFVEAIKKQDSNEKIETMRSLVKRLPPPNHDTMKILFRHLTKIVAKASQNLMSTQSLGIVFGPT 398
Cdd:cd04406    77 WLRDLPNPLMTFELYEEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPC 156

                  ...
gi 1395777151 399 LLR 401
Cdd:cd04406   157 ILR 159