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 1958657287  603 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 682
Cdd:cd13366      1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  683 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 761
Cdd:cd13366     81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                          170       180
                   ....*....|....*....|....*
gi 1958657287  762 SYLFLLSSDYERSEWREAIQKLQKK 786
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 1958657287  832 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 911
Cdd:cd08686      1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958657287  912 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 952
Cdd:cd08686     78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

Bcr-Abl oncoprotein oligomerization domain; The Bcr-Abl oncoprotein oligomerization domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerization domain is essential for the oncogenicity of the Bcr-Abl protein.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657287    3 DPQEFERHWQAEFPGEEAPVMKLESVPDMERELERCKLNLKRLQQVLAEEKFKVWYLQAALAGER 67
Cdd:pfam09036    1 EPAGFERHWRAEFPEGQVPKMELGSVEDIEQELERCKASLRRLQQELNEEKFKVIYLQTLLARER 65

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 1958657287  603 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 682
Cdd:cd13366      1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  683 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 761
Cdd:cd13366     81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                          170       180
                   ....*....|....*....|....*
gi 1958657287  762 SYLFLLSSDYERSEWREAIQKLQKK 786
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 1958657287  832 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 911
Cdd:cd08686      1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958657287  912 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 952
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 1958657287   986 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 1065
Cdd:smart00324    3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657287  1066 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 1140
Cdd:smart00324   82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAS 156

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; 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. Improved coverage.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287   421 VLSGFLASEEIYINQLEALL-LPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGH 498
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVeVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287   499 LFQKLASQLGVYKAFVDNYKVALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHD 578
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 1958657287   579 LLKHTPVDHPDYPLLQDALRISQNFLSSINE 609
Cdd:smart00325  150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 180

Bcr-Abl oncoprotein oligomerization domain; The Bcr-Abl oncoprotein oligomerization domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerization domain is essential for the oncogenicity of the Bcr-Abl protein.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657287    3 DPQEFERHWQAEFPGEEAPVMKLESVPDMERELERCKLNLKRLQQVLAEEKFKVWYLQAALAGER 67
Cdd:pfam09036    1 EPAGFERHWRAEFPEGQVPKMELGSVEDIEQELERCKASLRRLQQELNEEKFKVIYLQTLLARER 65

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  830 GFLHVIVHSAKG-----FKQSANLYCTLEVDSFgyfVSKAKTRVFRDTTEPKWDEEFEIEL--EGSQSLRIlcyeKCYDK 902
Cdd:pfam00168    1 GRLTVTVIEAKNlppkdGNGTSDPYVKVYLLDG---KQKKKTKVVKNTLNPVWNETFTFSVpdPENAVLEI----EVYDY 73

                           90       100
                   ....*....|....*....|....
gi 1958657287  903 TKVNKdnneivDKIMGKGQIQLDP 926
Cdd:pfam00168   74 DRFGR------DDFIGEVRIPLSE 91

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  830 GFLHVIVHSAKGFKQSANlycTLEVDSFGYFV------SKAKTRVFRDTTEPKWDEEFEIELEG-SQSLRIlcyeKCYDK 902
Cdd:COG5038    436 GVVEVKIKSAEGLKKSDS---TINGTVDPYITvtfsdrVIGKTRVKKNTLNPVWNETFYILLNSfTDPLNL----SLYDF 508

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1958657287  903 TKVNKdnneivDKIMGKgqIQLDPQTVESKNWHTDViemngiKVEFSMKF 952
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 1958657287  603 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 682
Cdd:cd13366      1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  683 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 761
Cdd:cd13366     81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                          170       180
                   ....*....|....*....|....*
gi 1958657287  762 SYLFLLSSDYERSEWREAIQKLQKK 786
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 1958657287  603 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 682
Cdd:cd13367      1 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLLLCAKLKKQIGGKSQQYDCKWYIPLADLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  683 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEK-ANKGqSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 761
Cdd:cd13367     81 FQTVDESEAVPNIPLIPDEEIDALKVKISQIKSDIQREKrANKG-GKVLERLRKKLSEQESLLLLMSPSMAFRVHNRNGK 159

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1958657287  762 SYLFLLSSDYERSEWREAIQKLQKKDLQAFVLSSV 796
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 1958657287  832 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 911
Cdd:cd08686      1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958657287  912 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 952
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 1958657287   986 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 1065
Cdd:smart00324    3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657287  1066 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 1140
Cdd:smart00324   82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAS 156

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 1958657287  971 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDM---DINAIAGTL 1047
Cdd:cd04398      1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPEDyesDIHSVASLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287 1048 KLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFG 1127
Cdd:cd04398     81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1958657287 1128 PTLLrpsevesKAHLTSAADIwSHDVMAqVQVLLYY 1163
Cdd:cd04398    161 PTLM-------NAAPDNAADM-SFQSRV-IETLLDN 187

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 1958657287  971 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDillmlSDM------DINAIA 1044
Cdd:cd04372      1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEK-----ADIsatvypDINVIT 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287 1045 GTLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLAT 1124
Cdd:cd04372     76 GALKLYFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGI 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1958657287 1125 VFGPTLLRPSEVESKAHLtsaadiwsHDVMAQVQVLLYYLQHPPISF 1171
Cdd:cd04372    156 VFGPTLMRPPEDSALTTL--------NDMRYQILIVQLLITNEDVLF 194

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        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  418 RKLVLSGFLASEEIYINQLEALLLP-MKPLKATATTsqpvLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVT 495
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVfLKPLDKELLP----LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDkSGPR 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  496 MGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKvkgpkdskDSHTSVTMEALLYKPIDRVTRSTLV 575
Cdd:cd00160     77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAE--------SECGRLKLESLLLKPVQRLTKYPLL 148

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1958657287  576 LHDLLKHTPVDHPDYPLLQDALRISQNFLSSIN 608
Cdd:cd00160    149 LKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; 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. Improved coverage.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287   421 VLSGFLASEEIYINQLEALL-LPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGH 498
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVeVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287   499 LFQKLASQLGVYKAFVDNYKVALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHD 578
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 1958657287   579 LLKHTPVDHPDYPLLQDALRISQNFLSSINE 609
Cdd:smart00325  150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 180

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 1958657287  986 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFdaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 1065
Cdd:cd04382     17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKF--LRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657287 1066 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKePINKMSLHNLATVFGPTL 1130
Cdd:cd04382     95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQS-PECKMDINNLARVFGPTI 158

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287  971 FGVKISVVTKRERSK--VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDM-DINAIAGTL 1047
Cdd:cd04379      1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYpDINVITGVL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287 1048 KLYFRELPEPLLTDRLYPAFMEGIALSDPAAKEnCMMHLLRS----LPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLA 1123
Cdd:cd04379     81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQ-TNTHLTLSiidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLA 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1958657287 1124 TVFGPTLLRPSEVESKAHLTSAADIW---SHDVMAQVQVLLYYLQ 1165
Cdd:cd04379    160 VCFGPVLMFCSQEFSRYGISPTSKMAavsTVDFKQHIEVLHYLLQ 204

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 1958657287  970 VFGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEvGIYRISGVATDIQALKAVFDANN-KDILLMLSDMDINAIAGTLK 1048
Cdd:cd04384      2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQiPDLTKDVYIQDIHSVSSLCK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287 1049 LYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGP 1128
Cdd:cd04384     81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1958657287 1129 TLLRPSEVESKAHLTSAADIwshDVMAQVQVLLYYLQH 1166
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 1958657287  970 VFGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKL 1049
Cdd:cd04386      4 VFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFYSDPHAVASALKS 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657287 1050 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 1129
Cdd:cd04386     84 YLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPN 163

                          170
                   ....*....|.
gi 1958657287 1130 LLRPSEVESKA 1140
Cdd:cd04386    164 LLWAKNEGSLA 174