Active breakpoint cluster region-related protein pleckstrin homology (PH) domain; The ABR protein contains multiple domains including a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. It is related to a slightly larger protein, BCR, which is structurally similar, but has an additional N-terminal kinase domain. ABR has GAP activity for both Rac and Cdc42. It promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. It is highly enriched in the brain and found to a lesser extent in heart, lung and muscle. 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 600971669  59 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 138
Cdd:cd13366    1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 139 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 217
Cdd:cd13366   81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                        170       180
                 ....*....|....*....|....*
gi 600971669 218 SYLFLLSSDYERSEWREAIQKLQKK 242
Cdd:cd13366  161 SYLFLLSSDYERSEWREAIQKLQKK 185

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 288 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 367
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 600971669 368 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 408
Cdd:cd08686   78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

Active breakpoint cluster region-related protein pleckstrin homology (PH) domain; The ABR protein contains multiple domains including a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. It is related to a slightly larger protein, BCR, which is structurally similar, but has an additional N-terminal kinase domain. ABR has GAP activity for both Rac and Cdc42. It promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. It is highly enriched in the brain and found to a lesser extent in heart, lung and muscle. 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 600971669  59 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 138
Cdd:cd13366    1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 139 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 217
Cdd:cd13366   81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                        170       180
                 ....*....|....*....|....*
gi 600971669 218 SYLFLLSSDYERSEWREAIQKLQKK 242
Cdd:cd13366  161 SYLFLLSSDYERSEWREAIQKLQKK 185

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 288 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 367
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 600971669 368 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 408
Cdd:cd08686   78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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 600971669   442 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 521
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 600971669   522 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 596
Cdd:smart00324  82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAS 156

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 600971669  17 LLYKPIDRVTRSTLVLHDLLKHTPVDHPDYPLLQDALRISQNFLSSIN 64
Cdd:cd00160  134 LLLKPVQRLTKYPLLLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669   287 FLHVIVHSAKGFK-----QSANLYCTLEVDsfGYFVSKAKTRVFRDTTEPKWDEEFEIEL--EGSQSLRIlcyeKCYDKT 359
Cdd:smart00239   1 TLTVKIISARNLPpkdkgGKSDPYVKVSLD--GDPKEKKKTKVVKNTLNPVWNETFEFEVppPELAELEI----EVYDKD 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 600971669   360 KVNKDnneivDKImgkGQIQLDPQTVESKNWH 391
Cdd:smart00239  75 RFGRD-----DFI---GQVTIPLSDLLLGGRH 98

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 600971669    84 LVKDGFLVEMSES---SRKLRHVFLFTDVLLCAKLKKtsagKHQQYDCKWYIPLADLvfpspeeseaspQVHPFPDHELE 160
Cdd:smart00233   1 VIKEGWLYKKSGGgkkSWKKRYFVLFNSTLLYYKSKK----DKKSYKPKGSIDLSGC------------TVREAPDPDSS 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669   161 DMKtkisalkseiqkekankgqsraierlkkkmfenefllllnsptIPFRIHNRNGKSYLFLLSSDYERSEWREAIQKLQ 240
Cdd:smart00233  65 KKP-------------------------------------------HCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101

                   .
gi 600971669   241 K 241
Cdd:smart00233 102 A 102

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669  286 GFLHVIVHSAKGFKQSANlycTLEVDSFGYFV------SKAKTRVFRDTTEPKWDEEFEIELEG-SQSLRIlcyeKCYDK 358
Cdd:COG5038   436 GVVEVKIKSAEGLKKSDS---TINGTVDPYITvtfsdrVIGKTRVKKNTLNPVWNETFYILLNSfTDPLNL----SLYDF 508

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 600971669  359 TKVNKdnneivDKIMGKgqIQLDPQTVESKNWHTDViemngiKVEFSMKF 408
Cdd:COG5038   509 NSFKS------DKVVGS--TQLDLALLHQNPVKKNE------LYEFLRNT 544

Active breakpoint cluster region-related protein pleckstrin homology (PH) domain; The ABR protein contains multiple domains including a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. It is related to a slightly larger protein, BCR, which is structurally similar, but has an additional N-terminal kinase domain. ABR has GAP activity for both Rac and Cdc42. It promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. It is highly enriched in the brain and found to a lesser extent in heart, lung and muscle. 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 600971669  59 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 138
Cdd:cd13366    1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 139 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 217
Cdd:cd13366   81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                        170       180
                 ....*....|....*....|....*
gi 600971669 218 SYLFLLSSDYERSEWREAIQKLQKK 242
Cdd:cd13366  161 SYLFLLSSDYERSEWREAIQKLQKK 185

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of vertebrate BCRs. 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 600971669  59 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 138
Cdd:cd13367    1 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLLLCAKLKKQIGGKSQQYDCKWYIPLADLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 139 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEK-ANKGqSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 217
Cdd:cd13367   81 FQTVDESEAVPNIPLIPDEEIDALKVKISQIKSDIQREKrANKG-GKVLERLRKKLSEQESLLLLMSPSMAFRVHNRNGK 159

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 600971669 218 SYLFLLSSDYERSEWREAIQKLQKKDLQAFVLSSV 252
Cdd:cd13367  160 SYTFLISSDYERAEWRENIREQQKKCFKSFSLTSL 194

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 288 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 367
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 600971669 368 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 408
Cdd:cd08686   78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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 600971669   442 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 521
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 600971669   522 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 596
Cdd:smart00324  82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAS 156

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. 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 600971669 427 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKLY 506
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 507 FRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTL 586
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 600971669 587 LRPsEVESkahltsaADIWSHDVMaQVQVLLYYLQ 621
Cdd:cd04403  161 LRP-EQET-------GNIAVHMVY-QNQIVELILL 186

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 600971669 427 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDAN-NKDILLMLSDMDINAIAGTLKL 505
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 506 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 585
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 600971669 586 LLRPSEVESKAHLtsaadiwsHDVMAQVQVLLYYLQHPPISF 627
Cdd:cd04372  161 LMRPPEDSALTTL--------NDMRYQILIVQLLITNEDVLF 194

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 600971669 426 VFGVKI-SVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAvfDANNKDILLMLSD---MDINAIAG 501
Cdd:cd04395    1 TFGVPLdDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQE--ELNRGGFDIDLQDprwRDVNVVSS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 502 TLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATV 581
Cdd:cd04395   79 LLKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIV 158

                        170
                 ....*....|
gi 600971669 582 FGPTLLRPSE 591
Cdd:cd04395  159 FGPTLVRTSD 168

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 600971669 442 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFdaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 521
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKF--LRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 600971669 522 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKePINKMSLHNLATVFGPTL 586
Cdd:cd04382   95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQS-PECKMDINNLARVFGPTI 158

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 600971669 426 VFGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEvGIYRISGVATDIQALKAVFDANN-KDILLMLSDMDINAIAGTLK 504
Cdd:cd04384    2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQiPDLTKDVYIQDIHSVSSLCK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 505 LYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGP 584
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 600971669 585 TLLRPSEVESKAHLTSAADIwshDVMAQVQVLLYYLQH 622
Cdd:cd04384  161 NLLRSKQIESACFSGTAAFM---EVRIQSVVVEFILNH 195

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. 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 600971669 426 VFGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKL 505
Cdd:cd04386    4 VFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFYSDPHAVASALKS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 506 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 585
Cdd:cd04386   84 YLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPN 163

                        170
                 ....*....|.
gi 600971669 586 LLRPSEVESKA 596
Cdd:cd04386  164 LLWAKNEGSLA 174

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 600971669 439 RSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDR 518
Cdd:cd04385   12 DNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFLRDLPDPLLTSE 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 519 LYPAFMEGIALSDpaAKENCMM--HLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 596
Cdd:cd04385   92 LHAEWIEAAELEN--KDERIARykELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQ 169

                 .
gi 600971669 597 H 597
Cdd:cd04385  170 T 170

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 600971669 427 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDiLLMLSDMDINAIAGTLKLY 506
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFE-NGRD-LVDLSGHSPHDITSVLKHF 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 507 FRELPEPLLTDRLYPAFM----EGIALSDPAAKENC--------MMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMS 574
Cdd:cd04408   79 LKELPEPVLPFQLYDDFIalakELQRDSEKAAESPSiveniirsLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMS 158

                        170
                 ....*....|....*
gi 600971669 575 LHNLATVFGPTLLRP 589
Cdd:cd04408  159 PNNLGIVFGPTLLRP 173

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 600971669 427 FGVKISVVTKRERS----KVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKdilLMLSDMDINAIAGT 502
Cdd:cd04381    1 FGASLSLAVERSRChdgiDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRES---PNLEEYEPPTVASL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 503 LKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVF 582
Cdd:cd04381   78 LKQYLRELPEPLLTKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVL 157

                 ....
gi 600971669 583 GPTL 586
Cdd:cd04381  158 SPTV 161

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 600971669 426 VFGVKISVVTKRER-----SKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIA 500
Cdd:cd04391    1 LFGVPLSTLLERDQkkvpgSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEGTFLWDQVKQHDAA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 600971669 501 GTLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLAT 580
Cdd:cd04391   81 SLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAM 160

                        170       180
                 ....*....|....*....|....*...
gi 600971669 581 VFGPTL-----LRPSEVESKA-HLTSAA 602
Cdd:cd04391  161 IMAPNLfpprgKHSKDNESLQeEVNMAA 188