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 564374722 281 KAGVLHRTKTVDKGKRLRKkHWNASWTVLEGGVLTFFKDSKTSAASGLRQpsklSTPEYTVELRGASLSWAPkDKSSKKN 360
Cdd:cd13233    2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGNPY----SKPESSVDLRGASIEWAK-EKSSRKN 75

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564374722 361 VLELRSRDGSEYLIQHDSEAIISTWHKAIAEGIEE 395
Cdd:cd13233   76 VFQISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

Splicing factor [RNA processing and modification];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722  42 SAAAPPRLSPVWETHTDAgTGRPYYYNPDTGVTTWESPFEapegatspttsrasVGSGESL---ETEWGQYwDEESGRVF 118
Cdd:COG5104    6 LGMASGEARSEWEELKAP-DGRIYYYNKRTGKSSWEKPKE--------------LLKGSEEdldVDPWKEC-RTADGKVY 69

                         90
                 ....*....|.
gi 564374722 119 FYNPLTGETVW 129
Cdd:COG5104   70 YYNSITRESRW 80

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 564374722   489 SPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGrWEDVHVITGALKLFFRELPEPLFPFSH 568
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLS-EYDVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722   569 FHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVFGPTLLRPEMEEASMPMT 648
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 564374722   649 MVFQNQVVELILHQC 663
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

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 564374722 281 KAGVLHRTKTVDKGKRLRKkHWNASWTVLEGGVLTFFKDSKTSAASGLRQpsklSTPEYTVELRGASLSWAPkDKSSKKN 360
Cdd:cd13233    2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGNPY----SKPESSVDLRGASIEWAK-EKSSRKN 75

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564374722 361 VLELRSRDGSEYLIQHDSEAIISTWHKAIAEGIEE 395
Cdd:cd13233   76 VFQISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 564374722   49 LSPVWETHTDAgTGRPYYYNPDTGVTTWESP 79
Cdd:pfam00397   1 LPPGWEERWDP-DGRVYYYNHETGETQWEKP 30

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                         10        20
                 ....*....|....*....|....*....
gi 564374722  51 PVWETHTDAgTGRPYYYNPDTGVTTWESP 79
Cdd:cd00201    2 PGWEERWDP-DGRVYYYNHNTKETQWEDP 29

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722  281 KAGVLHRtKTVDKGKRLRKKhwnasWTVLEGGVLTFFKDSKTsaasglrqpSKLSTPEYTVELRGASLSWAPK-DKSSKK 359
Cdd:pfam00169   3 KEGWLLK-KGGGKKKSWKKR-----YFVLFDGSLLYYKDDKS---------GKSKEPKGSISLSGCEVVEVVAsDSPKRK 67

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 564374722  360 NVLELRSRDGSE---YLIQHDSEAIISTWHKAIAEGIE 394
Cdd:pfam00169  68 FCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAIR 105

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                          10        20
                  ....*....|....*....|....*...
gi 564374722  219 EQWVRLEDQEGKPYFYNPEDSSVQWELP 246
Cdd:pfam00397   3 PGWEERWDPDGRVYYYNHETGETQWEKP 30

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                         10        20
                 ....*....|....*....|....*.
gi 564374722 221 WVRLEDQEGKPYFYNPEDSSVQWELP 246
Cdd:cd00201    4 WEERWDPDGRVYYYNHNTKETQWEDP 29

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 564374722   489 SPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGrWEDVHVITGALKLFFRELPEPLFPFSH 568
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLS-EYDVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722   569 FHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVFGPTLLRPEMEEASMPMT 648
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 564374722   649 MVFQNQVVELILHQC 663
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 492 PRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDErlDLDDGRWEDVHVITGALKLFFRELPEPLFPFSHFHQ 571
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 572 FIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVFGPTLLRPEMEEASMPMTMVF 651
Cdd:cd00159   79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                 ....*....
gi 564374722 652 QNQVVELIL 660
Cdd:cd00159  159 LNEIVEFLI 167

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 564374722 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGR--WE-DVHVITGAL 552
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPedYEsDIHSVASLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 553 KLFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVFG 632
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 564374722 633 PTLLRPEMEEASmpmTMVFQNQVVELILHQCADIF 667
Cdd:cd04398  161 PTLMNAAPDNAA---DMSFQSRVIETLLDNAYQIF 192

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 564374722 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGRWEDVHVITGALKLF 555
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 556 FRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVFGPTL 635
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                        170       180
                 ....*....|....*....|...
gi 564374722 636 LRPEMEEASMPMTMVFQNQVVEL 658
Cdd:cd04387  161 LRPSEKESKIPTNTMTDSWSLEV 183

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 564374722 281 KAGVLHRTKTVDKGKRLRKkHWNASWTVLEGGVLTFFKDSKTSAASGLRQpsklSTPEYTVELRGASLSWAPkDKSSKKN 360
Cdd:cd13233    2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGNPY----SKPESSVDLRGASIEWAK-EKSSRKN 75

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564374722 361 VLELRSRDGSEYLIQHDSEAIISTWHKAIAEGIEE 395
Cdd:cd13233   76 VFQISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDgrwEDVHVITGALKL 554
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLvELSE---LSPHDISSVLKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 555 FFRELPEPLFPFSHFHQFIAAIK--LQDPAQRS------------RCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQN 620
Cdd:cd04378   78 FLRQLPEPLILFRLYNDFIALAKeiQRDTEEDKapntpievnriiRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 564374722 621 RMSVQNVAIVFGPTLLRPEMEEASMPMTMV----FQNQVVE-LILH 661
Cdd:cd04378  158 KMSPNNLGIVFGPTLIRPRPGDADVSLSSLvdygYQARLVEfLITN 203

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 564374722 474 QVFGCALAQLCER--ERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDgrWEDVHVITGA 551
Cdd:cd04404    4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQ--YEDVHLPAVI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 552 LKLFFRELPEPLFPFShFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVF 631
Cdd:cd04404   82 LKTFLRELPEPLLTFD-LYDDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 564374722 632 GPTLLRPemEEASMPMTMVFQ-NQVVELILHQCADIF 667
Cdd:cd04404  161 GPNLLWA--KDASMSLSAINPiNTFTKFLLDHQDEIF 195

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 564374722 491 VPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDER-LDLDDgrwEDVHVITGALKLFFRELPEPLFPFSHF 569
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTvPNLSK---VDIHVICGCLKDFLRSLKEPLITFALW 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 570 HQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEqNRMSVQNVAIVFGPTLLRPEMEEASmPMTM 649
Cdd:cd04382   94 KEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIVGYSVPNPD-PMTI 171

                        170
                 ....*....|....*.
gi 564374722 650 ----VFQNQVVELILH 661
Cdd:cd04382  172 lqdtVRQPRVVERLLE 187

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 564374722 475 VFGCALAQLCERERSPVPRFVQQCIRTVEARGLdIDGLYRISGNLATIQKLRYKVDHDERLDL-DDGRWEDVHVITGALK 553
Cdd:cd04384    2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLtKDVYIQDIHSVSSLCK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 554 LFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVAIVFGP 633
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                        170       180       190
                 ....*....|....*....|....*....|...
gi 564374722 634 TLLR-PEMEEASMPMTMVF-----QNQVVELIL 660
Cdd:cd04384  161 NLLRsKQIESACFSGTAAFmevriQSVVVEFIL 193

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 564374722 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDgrwEDVHVITGALKL 554
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLvDLSG---HSPHDITSVLKH 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 555 FFRELPEPLFPFSHFHQFIAAIK--LQDPAQRSRC----------VRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRM 622
Cdd:cd04408   78 FLKELPEPVLPFQLYDDFIALAKelQRDSEKAAESpsiveniirsLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKM 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 564374722 623 SVQNVAIVFGPTLLRPeMEEASMPMTMV----FQNQVVELIL 660
Cdd:cd04408  158 SPNNLGIVFGPTLLRP-LVGGDVSMICLldtgYQAQLVEFLI 198

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 564374722 475 VFGCALAQLCERER-----SPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDhdERLDLDDGRWEDVHV-- 547
Cdd:cd04391    1 LFGVPLSTLLERDQkkvpgSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELE--AKFYEGTFLWDQVKQhd 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 548 ITGALKLFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNV 627
Cdd:cd04391   79 AASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNV 158

                        170
                 ....*....|.
gi 564374722 628 AIVFGPTLLRP 638
Cdd:cd04391  159 AMIMAPNLFPP 169

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 564374722 476 FGCALAQLCERERS--PVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDGRWEDVHVITGAL 552
Cdd:cd04379    1 FGVPLSRLVEREGEsrDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374722 553 KLFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSrCVRDLVRT----LPAPNHDTLRLLIQHLCRVIEHGEQNRMSVQNVA 628
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQ-TNTHLTLSiidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLA 159

                        170
                 ....*....|
gi 564374722 629 IVFGPTLLRP 638
Cdd:cd04379  160 VCFGPVLMFC 169