RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary 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 1115538302 108 GIFGQRLEETVHHERKYGPRLAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTTDVHTVASL 187
Cdd:cd04390     1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 188 LKLYLRELPEPVVPFARYEDFLSCAQLLTKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLAT 267
Cdd:cd04390    81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1115538302 268 VFGPNILRPQVEDPVTIMEGTSLVQHLMTVLIRKHSQLF 306
Cdd:cd04390   161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 547 REHARRSEALQG---LVTELRAELCRQRTEYERSVKRIEEGSADLRKRMSRLEEELDQEKKKYIMLEIKLRNSERAREDA 623
Cdd:COG1196   291 YELLAELARLEQdiaRLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEA 370

                          90
                  ....*....|....
gi 1115538302 624 ERRNQLLQREMEEF 637
Cdd:COG1196   371 EAELAEAEEELEEL 384

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary 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 1115538302 108 GIFGQRLEETVHHERKYGPRLAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTTDVHTVASL 187
Cdd:cd04390     1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 188 LKLYLRELPEPVVPFARYEDFLSCAQLLTKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLAT 267
Cdd:cd04390    81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1115538302 268 VFGPNILRPQVEDPVTIMEGTSLVQHLMTVLIRKHSQLF 306
Cdd:cd04390   161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 130 PLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKP-LFDSTTDVHTVASLLKLYLRELPEPVVPFARYEDF 208
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVdLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 209 LSCAQLLTKDEGEGTLELAkqVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVFGPNILRPQV 278
Cdd:pfam00620  81 IEAAKLPDEEERLEALREL--LRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1115538302   38 VLKAGWLKKQRSIM-KNWQQRWFVLRGDQLFYYKDKDE---IKPQGFISLQGTQVTELPPGPEDPGKHLFEI 105
Cdd:smart00233   1 VIKEGWLYKKSGGGkKSWKKRYFVLFNSTLLYYKSKKDkksYKPKGSIDLSGCTVREAPDPDSSKKPHCFEI 72

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 547 REHARRSEALQG---LVTELRAELCRQRTEYERSVKRIEEGSADLRKRMSRLEEELDQEKKKYIMLEIKLRNSERAREDA 623
Cdd:COG1196   291 YELLAELARLEQdiaRLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEA 370

                          90
                  ....*....|....
gi 1115538302 624 ERRNQLLQREMEEF 637
Cdd:COG1196   371 EAELAEAEEELEEL 384

heat shock protein GrpE; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 508 PSPLPSSSEDPKSLDLDHSMDEAGAGASNSEPSEPDSPTREHARRSEALQGLVTELRAELCRQRTEYersvKRIeegSAD 587
Cdd:PRK14143   24 SPESSEEVTEQEAELTNPEGDAAEAESSPDSGSAASETAADNAARLAQLEQELESLKQELEELNSQY----MRI---AAD 96

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1115538302 588 L---RKRMSRLEEELDQEKKKYIMLEI--KLRNSERAR 620
Cdd:PRK14143   97 FdnfRKRTSREQEDLRLQLKCNTLSEIlpVVDNFERAR 134

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 547 REHARRSEALQGLVTELRAELCRQRTEYERSvkrIEEGSADLRKRMSRLEEELDQEKKKyiMLEIKLRNSERA-REDAER 625
Cdd:cd16269   204 RAKAEAAEQERKLLEEQQRELEQKLEDQERS---YEEHLRQLKEKMEEERENLLKEQER--ALESKLKEQEALlEEGFKE 278

                          90
                  ....*....|..
gi 1115538302 626 RNQLLQREMEEF 637
Cdd:cd16269   279 QAELLQEEIRSL 290

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary 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 1115538302 108 GIFGQRLEETVHHERKYGPRLAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTTDVHTVASL 187
Cdd:cd04390     1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 188 LKLYLRELPEPVVPFARYEDFLSCAQLLTKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLAT 267
Cdd:cd04390    81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1115538302 268 VFGPNILRPQVEDPVTIMEGTSLVQHLMTVLIRKHSQLF 306
Cdd:cd04390   161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

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 1115538302  130 PLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKP-LFDSTTDVHTVASLLKLYLRELPEPVVPFARYEDF 208
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPdLDLSEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302  209 LSCAQLLTKDEGEGTLELAkqVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVFGPNILRPQVEDPVTIMEgT 288
Cdd:smart00324  84 IEAAKLEDETERLRALREL--LSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD-I 160

                          170
                   ....*....|....
gi 1115538302  289 SLVQHLMTVLIRKH 302
Cdd:smart00324 161 RHQNTVIEFLIENA 174

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. 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 1115538302  36 GPVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDKDEIKPQGFISLQGTQVTELPPGPEDPGKHLFEISPGIFGQRLE 115
Cdd:cd13378     1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGAGDREK 80

                  ....*.
gi 1115538302 116 ETVHHE 121
Cdd:cd13378    81 VPMNHE 86

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. 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 1115538302  38 VLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDKDEIKPQGFISLQGTQVTELPPGPEDPGKHLFEISPGIFGQRleET 117
Cdd:cd13263     3 PIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGGDR--MT 80

                  ....
gi 1115538302 118 VHHE 121
Cdd:cd13263    81 SNHD 84

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 1115538302 110 FGQRLEETVHHERKYGPrlAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTTDVHTVASLLK 189
Cdd:cd04404     6 FGVSLQFLKEKNPEQEP--IPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILK 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 190 LYLRELPEPVVPFARYEDFLSCAQLLTKDEGEGTLELakqVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVF 269
Cdd:cd04404    84 TFLRELPEPLLTFDLYDDIVGFLNVDKEERVERVKQL---LQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                  ....*...
gi 1115538302 270 GPNILRPQ 277
Cdd:cd04404   161 GPNLLWAK 168

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 1115538302 108 GIFGQRLEETVhherKYGPRLAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFD--STTDVHTVA 185
Cdd:cd04383     1 KLFNGSLEEYI----QDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADdqNDHDINSVA 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 186 SLLKLYLRELPEPVVPFARYEDFLSCAQLltKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNL 265
Cdd:cd04383    77 GVLKLYFRGLENPLFPKERFEDLMSCVKL--ENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNL 154

                         170
                  ....*....|....*...
gi 1115538302 266 ATVFGPNILR-PQVEDPV 282
Cdd:cd04383   155 AICFGPTLMPvPEGQDQV 172

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 1115538302 110 FGQRLEET-VHHERKYgprlAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCG--EKPLFDST-TDVHTVA 185
Cdd:cd04395     2 FGVPLDDCpPSSENPY----VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDPRwRDVNVVS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 186 SLLKLYLRELPEPVVPFARYEDFLSCAQLltKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNL 265
Cdd:cd04395    78 SLLKSFFRKLPEPLFTNELYPDFIEANRI--EDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNL 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1115538302 266 ATVFGPNILRPQvEDPVTIMegtslVQHL------MTVLIRKHSQLF 306
Cdd:cd04395   156 AIVFGPTLVRTS-DDNMETM-----VTHMpdqckiVETLIQHYDWFF 196

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 130 PLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDC-GEKPLFDSTT--DVHTVASLLKLYLRELPEPVVPFARYE 206
Cdd:cd04372    17 PMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRdGEKADISATVypDINVITGALKLYFRDLPIPVITYDTYP 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 207 DFLSCAQLLTKDEgegTLELAKQ-VSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVFGPNILRPQVEDPVTIM 285
Cdd:cd04372    97 KFIDAAKISNPDE---RLEAVHEaLMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSALTTL 173

                         170       180
                  ....*....|....*....|.
gi 1115538302 286 EGTSLVQHLMTVLIRKHSQLF 306
Cdd:cd04372   174 NDMRYQILIVQLLITNEDVLF 194

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 130 PLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTTDVHTVASLLKLYLRELPEPVVPFARYEDFL 209
Cdd:cd04376    10 PRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAFI 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 210 ScAQLLTKDEGEGTLELAKQVsnLPQANYNLLRYICKFLDEVQAYSNV-----------NKMSVQNLATVFGPNILRPQ- 277
Cdd:cd04376    90 G-TALLEPDEQLEALQLLIYL--LPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHKQk 166

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1115538302 278 ------VEDPVTIMEGTSLVQHLMTvLIRKHSQLFTAP 309
Cdd:cd04376   167 sgerefVQASLRIEESTAIINVVQT-MIDNYEELFMVS 203

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. 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 1115538302  38 VLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDKDEIKPQGFISLQGTQVTELPPGPEDPGKHLFEISPGifGQRLEET 117
Cdd:cd13379     3 VIKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEHPCNEEEPGKFLFEVVPG--GDRERMT 80

                  ....
gi 1115538302 118 VHHE 121
Cdd:cd13379    81 ANHE 84

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 1115538302 123 KYGPRLAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGeKPLFD-STTDVHTVASLLKLYLRELPEPVVP 201
Cdd:cd04378    10 RDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENG-KDLVElSELSPHDISSVLKLFLRQLPEPLIL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 202 FARYEDFLSCAQLLTKDEGEGT------------LELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVF 269
Cdd:cd04378    89 FRLYNDFIALAKEIQRDTEEDKapntpievnriiRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVF 168

                         170       180
                  ....*....|....*....|...
gi 1115538302 270 GPNILRPQVED-PVTImegTSLV 291
Cdd:cd04378   169 GPTLIRPRPGDaDVSL---SSLV 188

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 1115538302 130 PLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTTDVHTVASLLKLYLRELPEPVVPFARYEDFL 209
Cdd:cd04407    16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDFL 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 210 SCAQLLTKDEgegtlELA---KQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVFGPNILR-PQVEDPVTIM 285
Cdd:cd04407    96 RAVELPEKQE-----QLQaiyRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRcPDSSDPLTSM 170

                         170
                  ....*....|....*.
gi 1115538302 286 EGTSLVQHLMTVLIRK 301
Cdd:cd04407   171 KDVAKTTTCVEMLIKE 186

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. 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 1115538302 130 PLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGE---KPLFDSTTDVHTVASLLKLYLRELPEPVVPFARYE 206
Cdd:cd04396    33 PVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPdygKSFDWDGYTVHDAASVLRRYLNNLPEPLVPLDLYE 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 207 DF---------------LSCAQLLTKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVFGP 271
Cdd:cd04396   113 EFrnplrkrprilqymkGRINEPLNTDIDQAIKEYRDLITRLPNLNRQLLLYLLDLLAVFARNSDKNLMTASNLAAIFQP 192

                  ...
gi 1115538302 272 NIL 274
Cdd:cd04396   193 GIL 195

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. 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 1115538302 126 PRLAPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDC-GEKPLFDSTTDVHTVASLLKLYLRELPEPVVPFAR 204
Cdd:cd04373    12 EKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQdHNLDLVSKDFTVNAVAGALKSFFSELPDPLIPYSM 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 205 YEDFLSCAQLLtkDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNLATVFGPNILRPQVEDpVTI 284
Cdd:cd04373    92 HLELVEAAKIN--DREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMRPDFTS-MEA 168

                         170
                  ....*....|....*
gi 1115538302 285 MEGTSLVQHLMTVLI 299
Cdd:cd04373   169 LSATRIYQTIIETFI 183

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. 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 1115538302 110 FGQRLEETVHHERKY-GPRLaPLLVEQCVDFIRERGLTEEGLFRMPGQANLVRDLQDSFDCGEKPLFDSTtDVHTVASLL 188
Cdd:cd04381     1 FGASLSLAVERSRCHdGIDL-PLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLEEY-EPPTVASLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1115538302 189 KLYLRELPEPVVP---FARYEDflSCAqllTKDEGEGTLELAKQVSNLPQANYNLLRYICKFLDEVQAYSNVNKMSVQNL 265
Cdd:cd04381    79 KQYLRELPEPLLTkelMPRFEE--ACG---RPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNI 153

                  ....*...
gi 1115538302 266 ATVFGPNI 273
Cdd:cd04381   154 SIVLSPTV 161