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 83776555 281 KAGVLHRTKTVDKGKRLRKkHWSTSWTVLEGGVLTFFKDSKTSAAGGLRQpsklSTPEYTVELKGASLSWAPkDKSSKKN 360
Cdd:cd13233   2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGNPY----SKPESSVDLRGASIEWAK-EKSSRKN 75

                        90       100       110
                ....*....|....*....|....*....|....*
gi 83776555 361 VLELRSRDGSEYLIQHDSEAIISTWHKAIAEGISE 395
Cdd:cd13233  76 VFQISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

Splicing factor [RNA processing and modification];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555  42 SAAAPPRLSPVWEThTDTGTGRPYYYNPDTGVTTWESPFEtpegttspatsrasVGSGESL---ETEWGQYWDEESrRVF 118
Cdd:COG5104   6 LGMASGEARSEWEE-LKAPDGRIYYYNKRTGKSSWEKPKE--------------LLKGSEEdldVDPWKECRTADG-KVY 69

                        90
                ....*....|.
gi 83776555 119 FYNPLTGETAW 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 83776555    489 SPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGrWEDVHVITGALKLFFRELPEPLFPFSH 568
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLS-EYDVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555    569 FHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGPTLLRPEMEEASMPMT 648
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 83776555    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 83776555 281 KAGVLHRTKTVDKGKRLRKkHWSTSWTVLEGGVLTFFKDSKTSAAGGLRQpsklSTPEYTVELKGASLSWAPkDKSSKKN 360
Cdd:cd13233   2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGNPY----SKPESSVDLRGASIEWAK-EKSSRKN 75

                        90       100       110
                ....*....|....*....|....*....|....*
gi 83776555 361 VLELRSRDGSEYLIQHDSEAIISTWHKAIAEGISE 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 83776555    49 LSPVWETHTDTgTGRPYYYNPDTGVTTWESP 79
Cdd:pfam00397   1 LPPGWEERWDP-DGRVYYYNHETGETQWEKP 30

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 83776555     49 LSPVWETHTDTgTGRPYYYNPDTGVTTWESP 79
Cdd:smart00456   2 LPPGWEERKDP-DGRPYYYNHETKETQWEKP 31

Splicing factor [RNA processing and modification];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555  42 SAAAPPRLSPVWEThTDTGTGRPYYYNPDTGVTTWESPFEtpegttspatsrasVGSGESL---ETEWGQYWDEESrRVF 118
Cdd:COG5104   6 LGMASGEARSEWEE-LKAPDGRIYYYNKRTGKSSWEKPKE--------------LLKGSEEdldVDPWKECRTADG-KVY 69

                        90
                ....*....|.
gi 83776555 119 FYNPLTGETAW 129
Cdd:COG5104  70 YYNSITRESRW 80

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20
                   ....*....|....*....|....*..
gi 83776555    221 WVRLEDQHGKPYFYNPEDSSVQWELPQ 247
Cdd:smart00456   6 WEERKDPDGRPYYYNHETKETQWEKPR 32

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 83776555 221 WVRLEDQHGKPYFYNPEDSSVQWELP 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 83776555    489 SPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGrWEDVHVITGALKLFFRELPEPLFPFSH 568
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLS-EYDVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555    569 FHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGPTLLRPEMEEASMPMT 648
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 83776555    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 83776555 492 PRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDErlDLDDGRWEDVHVITGALKLFFRELPEPLFPFSHFHQ 571
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 572 FIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGPTLLRPEMEEASMPMTMVF 651
Cdd:cd00159  79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                ....*....
gi 83776555 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 83776555 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGR--WE-DVHVITGAL 552
Cdd:cd04398   1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPedYEsDIHSVASLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 553 KLFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFG 632
Cdd:cd04398  81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                       170       180       190
                ....*....|....*....|....*....|....*
gi 83776555 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 83776555 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGRWEDVHVITGALKLF 555
Cdd:cd04387   1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 556 FRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGPTL 635
Cdd:cd04387  81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                       170       180
                ....*....|....*....|...
gi 83776555 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 83776555 281 KAGVLHRTKTVDKGKRLRKkHWSTSWTVLEGGVLTFFKDSKTSAAGGLRQpsklSTPEYTVELKGASLSWAPkDKSSKKN 360
Cdd:cd13233   2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGNPY----SKPESSVDLRGASIEWAK-EKSSRKN 75

                        90       100       110
                ....*....|....*....|....*....|....*
gi 83776555 361 VLELRSRDGSEYLIQHDSEAIISTWHKAIAEGISE 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 83776555 476 FGCALAQLCERERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDgrwEDVHVITGALKL 554
Cdd:cd04378   1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLvELSE---LSPHDISSVLKL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 555 FFRELPEPLFPFSHFHQFIAAIK--LQDPAQRS------------RCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQN 620
Cdd:cd04378  78 FLRQLPEPLILFRLYNDFIALAKeiQRDTEEDKapntpievnriiRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 83776555 621 RMTVQNVAIVFGPTLLRPEMEEASMPMTMV----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 83776555 474 QVFGCALAQLCER--ERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDgrWEDVHVITGA 551
Cdd:cd04404   4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQ--YEDVHLPAVI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 552 LKLFFRELPEPLFPFShFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVF 631
Cdd:cd04404  82 LKTFLRELPEPLLTFD-LYDDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 83776555 632 GPTLLRPemEEASMPMTMVFQ-NQVVELILHQCADIF 667
Cdd:cd04404 161 GPNLLWA--KDASMSLSAINPiNTFTKFLLDHQDEIF 195

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. 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 83776555 488 RSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHDER---LDLDDgrwEDVHVITGALKLFFRELPEPLF 564
Cdd:cd04385  12 DNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARsvqLREGE---YTVHDVADVLKRFLRDLPDPLL 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 565 PFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGPTLLRPE--MEE 642
Cdd:cd04385  89 TSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDehSVG 168

                       170
                ....*....|....*....
gi 83776555 643 ASMPMTMVfqnqVVELILH 661
Cdd:cd04385 169 QTSHEVKV----IEDLIDN 183

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 475 VFGCALAQLCERERSPVPRFVQQCIRTVEARGLdIDGLYRISGNLATIQKLRYKVDHDERLDL-DDGRWEDVHVITGALK 553
Cdd:cd04384   2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLtKDVYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 554 LFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGP 633
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                       170       180       190
                ....*....|....*....|....*....|...
gi 83776555 634 TLLR-PEMEEASMPMTMVF-----QNQVVELIL 660
Cdd:cd04384 161 NLLRsKQIESACFSGTAAFmevriQSVVVEFIL 193

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 83776555 475 VFGCALAQLCE-----RERSPVPRFVQQCIRTVEA-RGLDIDGLYRISGNLATIQKLRYKVDHDERLDL-DDGRWEDVHV 547
Cdd:cd04400   1 IFGSPLEEAVElsshkYNGRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLfSSSLYPDVHT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 548 ITGALKLFFRELPEPLFPFSHFHQFIAAIKLQ-DPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQN 626
Cdd:cd04400  81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENhDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                ....*....
gi 83776555 627 VAIVFGPTL 635
Cdd:cd04400 161 VCIVFSPTL 169

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 83776555 475 VFGCALAQLCERER-----SPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDhdERLDLDDGRWEDVHV-- 547
Cdd:cd04391   1 LFGVPLSTLLERDQkkvpgSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELE--AKFYEGTFLWDQVKQhd 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 548 ITGALKLFFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNV 627
Cdd:cd04391  79 AASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNV 158

                       170
                ....*....|.
gi 83776555 628 AIVFGPTLLRP 638
Cdd:cd04391 159 AMIMAPNLFPP 169

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 83776555 476 FGCALAQLCErERSPVPRFVQQCIRTVEARGLDIDGLYRISGNLATIQKLRYKVDHD-ERLDLDDgrwEDVHVITGALKL 554
Cdd:cd04407   1 FGVRVGSLTS-NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADpENVKLEN---YPIHAITGLLKQ 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83776555 555 FFRELPEPLFPFSHFHQFIAAIKLQDPAQRSRCVRDLVRTLPAPNQDTLRLLIQHLCRVIEHGEQNRMTVQNVAIVFGPT 634
Cdd:cd04407  77 WLRELPEPLMTFAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPC 156

                       170       180
                ....*....|....*....|....*...
gi 83776555 635 LLR-PEMEEASMPMTMVFQNQV-VELIL 660
Cdd:cd04407 157 LLRcPDSSDPLTSMKDVAKTTTcVEMLI 184