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 1870786120 242 KAGVLHRTKTADKGKRLRKkHWSASWTVLEGGVLTFFKDSKTSAAGGLrqpsKFSTPEYTVELRGATLSWAPkDKSSRKN 321
Cdd:cd13233     2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGN----PYSKPESSVDLRGASIEWAK-EKSSRKN 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1870786120 322 VLELRSRDGSEYLIQHDSEAIISTWHKAIAQGIQE 356
Cdd:cd13233    76 VFQISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120  24 PEPVYANIERQPRATSpGAAAAPLPSPVWETHTDAG-TGRPYYYNPDTGVTTWESPFEAAEGAASPATSPASVDSHPPTP 102
Cdd:PRK08691  385 AEKETAAKKPQPRPEA-ETAQTPVQTASAAAMPSEGkTAGPVSNQENNDVPPWEDAPDEAQTAAGTAQTSAKSIQTASEA 463

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 103 ETDYPESLTSYPEEDYSPVGSFGE-PGPTSPLTTPpgwschvsqDKQMLYTNHFTQEQWVRLEDPHGKPYF-YNPEDSSv 180
Cdd:PRK08691  464 ETPPENQVSKNKAADNETDAPLSEvPSENPIQATP---------NDEAVETETFAHEAPAEPFYGYGFPDNdCPPEDGA- 533

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1870786120 181 rwELPQVP----VPAPRSIHKSSQDGDTPAQASPPEEKVPAELDEVGSWEEV 228
Cdd:PRK08691  534 --EIPPPDwehaAPADTAGGGADEEAEAGGIGGNNTPSAPPPEFSTENWAAI 583

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 1870786120  451 SRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGrWEDVHVITGALKLFFRELPEPLFPFSH 530
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLS-EYDVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120  531 FRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTLLRPEVEETSMPMT 610
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 1870786120  611 MVFQNQVVELILQQC 625
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 1870786120 242 KAGVLHRTKTADKGKRLRKkHWSASWTVLEGGVLTFFKDSKTSAAGGLrqpsKFSTPEYTVELRGATLSWAPkDKSSRKN 321
Cdd:cd13233     2 KQGLLNKTKIAENGKKLRK-NWSTSWVVLTSSHLLFYKDAKSAAKSGN----PYSKPESSVDLRGASIEWAK-EKSSRKN 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1870786120 322 VLELRSRDGSEYLIQHDSEAIISTWHKAIAQGIQE 356
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 1870786120  47 LPSPvWETHTDAgTGRPYYYNPDTGVTTWESP 78
Cdd:pfam00397   1 LPPG-WEERWDP-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 1870786120  50 PVWETHTDAgTGRPYYYNPDTGVTTWESP 78
Cdd:cd00201     2 PGWEERWDP-DGRVYYYNHNTKETQWEDP 29

DNA polymerase III subunits gamma and tau; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120  24 PEPVYANIERQPRATSpGAAAAPLPSPVWETHTDAG-TGRPYYYNPDTGVTTWESPFEAAEGAASPATSPASVDSHPPTP 102
Cdd:PRK08691  385 AEKETAAKKPQPRPEA-ETAQTPVQTASAAAMPSEGkTAGPVSNQENNDVPPWEDAPDEAQTAAGTAQTSAKSIQTASEA 463

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 103 ETDYPESLTSYPEEDYSPVGSFGE-PGPTSPLTTPpgwschvsqDKQMLYTNHFTQEQWVRLEDPHGKPYF-YNPEDSSv 180
Cdd:PRK08691  464 ETPPENQVSKNKAADNETDAPLSEvPSENPIQATP---------NDEAVETETFAHEAPAEPFYGYGFPDNdCPPEDGA- 533

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1870786120 181 rwELPQVP----VPAPRSIHKSSQDGDTPAQASPPEEKVPAELDEVGSWEEV 228
Cdd:PRK08691  534 --EIPPPDwehaAPADTAGGGADEEAEAGGIGGNNTPSAPPPEFSTENWAAI 583

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

                           10        20
                   ....*....|....*....|....*..
gi 1870786120  160 WVRLEDPHGKPYFYNPEDSSVRWELPQ 186
Cdd:smart00456   6 WEERKDPDGRPYYYNHETKETQWEKPR 32

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 1870786120  451 SRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGrWEDVHVITGALKLFFRELPEPLFPFSH 530
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLS-EYDVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120  531 FRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTLLRPEVEETSMPMT 610
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 1870786120  611 MVFQNQVVELILQQC 625
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 1870786120 454 PRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDErlDLDDGRWEDVHVITGALKLFFRELPEPLFPFSHFRQ 533
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 534 FIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTLLRPEVEETSMPMTMVF 613
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                         170
                  ....*....|
gi 1870786120 614 QNQVVELILQ 623
Cdd:cd00159   159 LNEIVEFLIE 168

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 1870786120 452 RVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDH-DERLDLDDGRWEDVHVITGALKLFFRELPEPLFPFSH 530
Cdd:cd04395    17 YVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRgGFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNEL 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 531 FRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTLLRPEVEE-TSMPM 609
Cdd:cd04395    97 YPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNmETMVT 176

                         170
                  ....*....|....*.
gi 1870786120 610 TMVFQNQVVELILQQC 625
Cdd:cd04395   177 HMPDQCKIVETLIQHY 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 1870786120 438 FGCALAALCERERSRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGRWEDVHVITGALKLF 517
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 518 FRELPEPLFPFSHFRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTL 597
Cdd:cd04387    81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                         170       180
                  ....*....|....*....|....*.
gi 1870786120 598 LRPEVEETSMPMTMVFQNQVVELILQ 623
Cdd:cd04387   161 LRPSEKESKIPTNTMTDSWSLEVMSQ 186

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 456 FVQQCIRAVEARGLDIDGLYRISGNLATIQKL-----RYKVDHDERLDLDDGRWEdVHVITGALKLFFRELPEPLFPFSH 530
Cdd:cd04374    31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLlslglDPKTSTPGDVDLDNSEWE-IKTITSALKTYLRNLPEPLMTYEL 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 531 FRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTLLRPEVEETSMPMT 610
Cdd:cd04374   110 HNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAIMD 189

                         170
                  ....*....|...
gi 1870786120 611 MVFQNQVVELILQ 623
Cdd:cd04374   190 IKFQNIVVEILIE 202

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 1870786120 438 FGCALAALCERERSRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDgrwEDVHVITGALKL 516
Cdd:cd04378     1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLvELSE---LSPHDISSVLKL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 517 FFRELPEPLFPFSHFRQFIAAIK-LQ----DQARRSRC---------VRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQN 582
Cdd:cd04378    78 FLRQLPEPLILFRLYNDFIALAKeIQrdteEDKAPNTPievnriirkLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1870786120 583 RMSVQSVAIVFGPTLLRPEVEETSMPMTMV----FQNQVVELILQ 623
Cdd:cd04378   158 KMSPNNLGIVFGPTLIRPRPGDADVSLSSLvdygYQARLVEFLIT 202

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 1870786120 436 QVFGCALAALCER--ERSRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDgrWEDVHVITGA 513
Cdd:cd04404     4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQ--YEDVHLPAVI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 514 LKLFFRELPEPLFPFSHFrQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVF 593
Cdd:cd04404    82 LKTFLRELPEPLLTFDLY-DDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1870786120 594 GPTLLRPevEETSMPMTMVFQ-NQVVELILQQCADIF 629
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 1870786120 452 RVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDER-LDLDDgrwEDVHVITGALKLFFRELPEPLFPFSH 530
Cdd:cd04382    16 MIPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTvPNLSK---VDIHVICGCLKDFLRSLKEPLITFAL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 531 FRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEqNRMSVQSVAIVFGPTLLRPEVEETSmPMT 610
Cdd:cd04382    93 WKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIVGYSVPNPD-PMT 170

                         170
                  ....*....|....*.
gi 1870786120 611 M----VFQNQVVELIL 622
Cdd:cd04382   171 IlqdtVRQPRVVERLL 186

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 1870786120 437 VFGCALAALCERERSRVPRFVQQCIRAVEARGLdIDGLYRISGNLATIQKLRYKVDHDERLDL-DDGRWEDVHVITGALK 515
Cdd:cd04384     2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLtKDVYIQDIHSVSSLCK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 516 LFFRELPEPLFPFSHFRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGP 595
Cdd:cd04384    81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1870786120 596 TLLR-PEVEETSMPMTMVF-----QNQVVELIL 622
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 1870786120 438 FGCALAALCERERSRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDgrwEDVHVITGALKL 516
Cdd:cd04408     1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLvDLSG---HSPHDITSVLKH 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 517 FFRELPEPLFPFSHFRQFIAAIK--LQDQARRSRC----------VRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRM 584
Cdd:cd04408    78 FLKELPEPVLPFQLYDDFIALAKelQRDSEKAAESpsiveniirsLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKM 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1870786120 585 SVQSVAIVFGPTLLRPEVEEtSMPMTMV----FQNQVVELILQ 623
Cdd:cd04408   158 SPNNLGIVFGPTLLRPLVGG-DVSMICLldtgYQAQLVEFLIS 199

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 1870786120 438 FGCALAALCErERSRVPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHD-ERLDLDDgrwEDVHVITGALKL 516
Cdd:cd04407     1 FGVRVGSLTS-NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADpENVKLEN---YPIHAITGLLKQ 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 517 FFRELPEPLFPFSHFRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPT 596
Cdd:cd04407    77 WLRELPEPLMTFAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPC 156

                         170       180       190
                  ....*....|....*....|....*....|
gi 1870786120 597 LLR-PEVEETSMPMTMVFQNQV-VELILQQ 624
Cdd:cd04407   157 LLRcPDSSDPLTSMKDVAKTTTcVEMLIKE 186

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 1870786120 438 FGCALAALCERERSR--VPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERL-DLDDGRWEDVHVITGAL 514
Cdd:cd04379     1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 515 KLFFRELPEPLFPFSHFRQFIAAIKLQDQARRSrCVRDLVRS----LPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVA 590
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQ-TNTHLTLSiidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLA 159

                         170
                  ....*....|
gi 1870786120 591 IVFGPTLLRP 600
Cdd:cd04379   160 VCFGPVLMFC 169

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. 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 1870786120 453 VPRFVQQCIRAVEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGRWEDVHVITGALKLFFRELPEPLFPFSHFR 532
Cdd:cd04383    18 IPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYFRGLENPLFPKERFE 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870786120 533 QFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNRMSVQSVAIVFGPTLLR-PEVEEtsmpmTM 611
Cdd:cd04383    98 DLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPvPEGQD-----QV 172