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 49523023  45 EKPVKSGWLKKQqKSFVKNWQQRYFVLKGQQLCFYKDLDDGKAQGCLFLPRSTVSEVSSSPDDAGKFIFQIIPASSMEHN 124
Cdd:cd13263   1 ERPIKSGWLKKQ-GSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGGDRM 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 49523023 125 KPIPDPYVLMANSQAEMEEWVKAIKRAAGFPSGAV 159
Cdd:cd13263  80 TSNHDSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

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 49523023  45 EKPVKSGWLKKQqKSFVKNWQQRYFVLKGQQLCFYKDLDDGKAQGCLFLPRSTVSEVSSSPDDAGKFIFQIIPASSMEHN 124
Cdd:cd13263   1 ERPIKSGWLKKQ-GSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGGDRM 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 49523023 125 KPIPDPYVLMANSQAEMEEWVKAIKRAAGFPSGAV 159
Cdd:cd13263  80 TSNHDSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023   180 PILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPS-FSSDTDVHTVASLFKLYLRELPEPAIPWRQYEDF 258
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDlDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 49523023   259 LSCEKMMSVDEEKghgELMNQ-ISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQT 328
Cdd:pfam00620  81 IEAAKLPDEEERL---EALRElLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023    47 PVKSGWLKKQQKSFVKNWQQRYFVLKGQQLCFYKD---LDDGKAQGCLFLPRSTVSEVSSSPDDAGKFIFQIIPASSMEH 123
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDdksGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGERTGK 80

                          90       100
                  ....*....|....*....|....*...
gi 49523023   124 NKpipdpYVLMANSQAEMEEWVKAIKRA 151
Cdd:pfam00169  81 RT-----YLLQAESEEERKDWIKAIQSA 103

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 49523023  45 EKPVKSGWLKKQqKSFVKNWQQRYFVLKGQQLCFYKDLDDGKAQGCLFLPRSTVSEVSSSPDDAGKFIFQIIPASSMEHN 124
Cdd:cd13263   1 ERPIKSGWLKKQ-GSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGGDRM 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 49523023 125 KPIPDPYVLMANSQAEMEEWVKAIKRAAGFPSGAV 159
Cdd:cd13263  80 TSNHDSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

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 49523023 180 PILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFSSDTDVHTVASLFKLYLRELPEPAIPWRQYEDFL 259
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 260 SCEKMMsvDEEKGHGELMNQISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQTEDPEALMRSaP 339
Cdd:cd00159  81 ELAKIE--DEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDI-K 157

                       170
                ....*....|..
gi 49523023 340 QIQRLLTVMISH 351
Cdd:cd00159 158 KLNEIVEFLIEN 169

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 49523023  45 EKPVKSGWLKKQqKSFVKNWQQRYFVLKGQQLCFYKDLDDGKAQGCLFLPRSTVSEVSSSPDDAGKFIFQIIPASSMEHN 124
Cdd:cd13378   1 EGVLKAGWLKKQ-RSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGAGDRE 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 49523023 125 K-PI-PDPYVLMANSQAEMEEWVKAIKRAAGFPSG 157
Cdd:cd13378  80 KvPMnHEAFLLMANSQSDMEDWVKAIRRVIWAPFG 114

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 49523023 171 EKKYGRHTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFSSDTDVHTVASLFKLYLRELPEPAI 250
Cdd:cd04404  15 EKNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILKTFLRELPEPLL 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 251 PWRQYEDFLsceKMMSVDEEKGHGELMNQISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQteD 330
Cdd:cd04404  95 TFDLYDDIV---GFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK--D 169

                       170       180
                ....*....|....*....|....*.
gi 49523023 331 PEALMRSAPQIQRLLTVMISHHEKFF 356
Cdd:cd04404 170 ASMSLSAINPINTFTKFLLDHQDEIF 195

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 176 RHTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFSSDTDVHTVASLFKLYLRELPEPAIPWRQY 255
Cdd:cd04393  17 ENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEADVCSAASLLRLFLQELPEGLIPASLQ 96

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 49523023 256 EDFLSCEKMMSVDEEKGHgELMNQISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQTeDPEAL 334
Cdd:cd04393  97 IRLMQLYQDYNGEDEFGR-KLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFGPDVFHVYT-DVEDM 173

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 49523023 160 FGQCLVDTITYEKKygrhTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGER-----PSFSSDTDVHTV 234
Cdd:cd04398   1 FGVPLEDLILREGD----NVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLnvlliSPEDYESDIHSV 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 235 ASLFKLYLRELPEPAIPWRQYEDFLSCekMMSVDEEKGHGELMNQISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDN 314
Cdd:cd04398  77 ASLLKLFFRELPEPLLTKALSREFIEA--AKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNN 154

                       170
                ....*....|....*.
gi 49523023 315 LSMVIGVNLLKPQTED 330
Cdd:cd04398 155 LAIIWGPTLMNAAPDN 170

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) 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 49523023 160 FGQCLVDTITYEK-KYGRHTVPILMEKCADFIRE-KGMDEEGIFRLPGQDNLVKQLKEAFDAGERPsFSSDTDVHTVASL 237
Cdd:cd04389   1 FGSSLEEIMDRQKeKYPELKLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYP-LSGLEDPHVPASL 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 238 FKLYLRELPEPAIPWRQYEDflscekmmSVDEEKGHGELMNQISILPKENYNLLCFICRFL--FEVQKNSSVNKMSVDNL 315
Cdd:cd04389  80 LKLWLRELEEPLIPDALYQQ--------CISASEDPDKAVEIVQKLPIINRLVLCYLINFLqvFAQPENVAHTKMDVSNL 151

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 49523023 316 SMVIGVNLLKPQTEDPEALMRSAPQIQRLLTVMISH 351
Cdd:cd04389 152 AMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLIEH 187

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 49523023 176 RHTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFS--SDTDVHTVASLFKLYLRELPEPAIPWR 253
Cdd:cd04387  13 RSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVmlSEMDVNAIAGTLKLYFRELPEPLFTDE 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 254 QYEDFLscEKMMSVDEEKGHGELMNQISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQTEDPEA 333
Cdd:cd04387  93 LYPNFA--EGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKI 170

                       170
                ....*....|.
gi 49523023 334 LMRSAPQIQRL 344
Cdd:cd04387 171 PTNTMTDSWSL 181

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 49523023 179 VPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFSSDTDVHTVASLFKLYLRELPEPAIPWRQYEDF 258
Cdd:cd04382  17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWKEF 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 259 LSCEKMMsvDEEKGHGELMNQISILPKENYNLLCFICRFLFEVQKnSSVNKMSVDNLSMVIG---VNLLKPQTeDPEALM 335
Cdd:cd04382  97 MEAAEIL--DEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGptiVGYSVPNP-DPMTIL 172

                       170
                ....*....|....*
gi 49523023 336 RSAPQIQRLLTVMIS 350
Cdd:cd04382 173 QDTVRQPRVVERLLE 187

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 179 VPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFSSDTDVHTVASLFKLYLRELPEPAIPWRQYEDF 258
Cdd:cd04376   9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 259 LSCEKmMSVDEEKGHGELMnqISILPKENYNLLCFICRFLFEVQKNS-----------SVNKMSVDNLSMVIGVNLLKPQ 327
Cdd:cd04376  89 IGTAL-LEPDEQLEALQLL--IYLLPPCNCDTLHRLLKFLHTVAEHAadsidedgqevSGNKMTSLNLATIFGPNLLHKQ 165

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 49523023 328 -------TEDPEALMRSAPQIQRLLTvMISHHEKFFPKSKDL 362
Cdd:cd04376 166 ksgerefVQASLRIEESTAIINVVQT-MIDNYEELFMVSPEL 206

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 49523023 179 VPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERpSFS---SDTDVHTVASLFKLYLRELPEPAIPWRQY 255
Cdd:cd04385  15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDAR-SVQlreGEYTVHDVADVLKRFLRDLPDPLLTSELH 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 256 EDFLSCEKMMSVDEE-KGHGELmnqISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQTEDPEAL 334
Cdd:cd04385  94 AEWIEAAELENKDERiARYKEL---IRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQT 170

                       170
                ....*....|..
gi 49523023 335 MRSAPQIQRLLT 346
Cdd:cd04385 171 SHEVKVIEDLID 182

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 49523023 160 FGQClVDTITYEKKygrhTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERPSFSSDTDVHTVASLFK 239
Cdd:cd04407   1 FGVR-VGSLTSNKT----SVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLK 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 240 LYLRELPEPAIPWRQYEDFLSCEKMMSVDEEKghGELMNQISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVI 319
Cdd:cd04407  76 QWLRELPEPLMTFAQYNDFLRAVELPEKQEQL--QAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVF 153

                       170       180       190
                ....*....|....*....|....*....|.
gi 49523023 320 GVNLLK-PQTEDPEALMRSAPQIQRLLTVMI 349
Cdd:cd04407 154 APCLLRcPDSSDPLTSMKDVAKTTTCVEMLI 184

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 49523023 177 HTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDA-GERPSFSSDT--DVHTVASLFKLYLRELPEPAIPWR 253
Cdd:cd04372  14 TQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRdGEKADISATVypDINVITGALKLYFRDLPIPVITYD 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 254 QYEDFLSCEKMMSVDE--EKGHGELMnqisILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKPQTEDP 331
Cdd:cd04372  94 TYPKFIDAAKISNPDErlEAVHEALM----LLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSA 169

                       170       180
                ....*....|....*....|....*
gi 49523023 332 EALMRSAPQIQRLLTVMISHHEKFF 356
Cdd:cd04372 170 LTTLNDMRYQILIVQLLITNEDVLF 194

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 49523023 179 VPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAGERP--SFSSDTDVHTVASLFKLYLRELPEPAIPWRQYE 256
Cdd:cd04383  18 IPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPlaDDQNDHDINSVAGVLKLYFRGLENPLFPKERFE 97

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 49523023 257 DFLSCEKMMSVDEEKGHGELMnqISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLK-PQTEDP 331
Cdd:cd04383  98 DLMSCVKLENPTERVHQIREI--LSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPvPEGQDQ 171

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 49523023 172 KKYGRHTVPILMEKCADFIREKGMDEEGIFRLPGQDNLVKQLKEAFDAgerPSFSSDTD-----VHTVASLFKLYLRELP 246
Cdd:cd04391  15 KKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEA---KFYEGTFLwdqvkQHDAASLLKLFIRELP 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023 247 EPAIPWRQYEDFLSCEKMMSVDEEKGHGELMnqISILPKENYNLLCFICRFLFEVQKNSSVNKMSVDNLSMVIGVNLLKP 326
Cdd:cd04391  92 QPLLTVEYLPAFYSVQGLPSKKDQLQALNLL--VLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFPP 169

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 49523023 327 QT------EDPEALMRSAPQIQRLLTVMISHHEKFFPKSKDL 362
Cdd:cd04391 170 RGkhskdnESLQEEVNMAAGCANIMRLLIRYQDLLWTVPSFL 211

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49523023     47 PVKSGWLKKQQKSFVKNWQQRYFVLKGQQLCFYKD---LDDGKAQGCLFLPRSTVSEVSSSPDDAGKFIFQIIPASsmeh 123
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSD---- 76

                           90       100
                   ....*....|....*....|....*....
gi 49523023    124 nkpiPDPYVLMANSQAEMEEWVKAIKRAA 152
Cdd:smart00233  77 ----RKTLLLQAESEEEREKWVEALRKAI 101