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 38679954 240 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 319
Cdd:cd13366   1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 320 FPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 398
Cdd:cd13366  81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                       170       180
                ....*....|....*....|....*
gi 38679954 399 SYLFLLSSDYERSEWREAIQKLQKK 423
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 38679954 469 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTAEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 548
Cdd:cd08686   1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 38679954 549 IVDKIMGKGQIQLDPQTVETKNWHTDVIEMNGIKVEFSMKF 589
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 38679954 240 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 319
Cdd:cd13366   1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 320 FPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 398
Cdd:cd13366  81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                       170       180
                ....*....|....*....|....*
gi 38679954 399 SYLFLLSSDYERSEWREAIQKLQKK 423
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 38679954 469 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTAEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 548
Cdd:cd08686   1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 38679954 549 IVDKIMGKGQIQLDPQTVETKNWHTDVIEMNGIKVEFSMKF 589
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 38679954    623 VPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 702
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38679954    703 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 777
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 38679954     58 VLSGFLASEEIYINQLEALL-LPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGH 135
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVeVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954    136 LFQKLASQLGVYKAFVDNYKVALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHD 215
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKE 149

                          170       180       190
                   ....*....|....*....|....*....|.
gi 38679954    216 LLKHTPVDHPDYPLLQDALRISQNFLSSINE 246
Cdd:smart00325 150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 180

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 38679954    468 FLHVIVHSAKGFK-----QSANLYCTLEVDsfGYFVSKAKTRVFRDTAEPKWDEEFEIEL--EGSQSLRIlcyeKCYDKT 540
Cdd:smart00239   1 TLTVKIISARNLPpkdkgGKSDPYVKVSLD--GDPKEKKKTKVVKNTLNPVWNETFEFEVppPELAELEI----EVYDKD 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 38679954    541 KVNKDnneivDKImgkGQIQLDPQTVETKNWH 572
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 38679954    265 LVKDGFLVEVSES---SRKLRHVFLFTDVLLCAKLKKtsagKHQQYDCKWYIPLADLvfpspeeseaspQVHPFPDHELE 341
Cdd:smart00233   1 VIKEGWLYKKSGGgkkSWKKRYFVLFNSTLLYYKSKK----DKKSYKPKGSIDLSGC------------TVREAPDPDSS 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954    342 DMKMkisalkseiqkekankgqsraierlkkkmfenefllllnsptiPFRIHNRNGKSYLFLLSSDYERSEWREAIQKLQ 421
Cdd:smart00233  65 KKPH-------------------------------------------CFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101

                   .
gi 38679954    422 K 422
Cdd:smart00233 102 A 102

PH domain; This entry contains a PH domain found in RhoGEF proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 38679954   261 ETRQLVKDGFLVEVSESSR------KLRHVFLFTDVLLCA--KLKKTSAGKH----QQYDCKWYIPLAD 317
Cdd:pfam19057   9 GQRYLIRQDDVVETVYNERgevlksKERRLFLLNDLLVCVtvNSKSGSDFGSlpggEKYKLKWSVPLSD 77

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 38679954 240 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 319
Cdd:cd13366   1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 320 FPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 398
Cdd:cd13366  81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                       170       180
                ....*....|....*....|....*
gi 38679954 399 SYLFLLSSDYERSEWREAIQKLQKK 423
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 38679954 240 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 319
Cdd:cd13367   1 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLLLCAKLKKQIGGKSQQYDCKWYIPLADLS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 320 FPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEK-ANKGqSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 398
Cdd:cd13367  81 FQTVDESEAVPNIPLIPDEEIDALKVKISQIKSDIQREKrANKG-GKVLERLRKKLSEQESLLLLMSPSMAFRVHNRNGK 159

                       170       180       190
                ....*....|....*....|....*....|....*
gi 38679954 399 SYLFLLSSDYERSEWREAIQKLQKKDLQAFVLSSV 433
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 38679954 469 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTAEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 548
Cdd:cd08686   1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 38679954 549 IVDKIMGKGQIQLDPQTVETKNWHTDVIEMNGIKVEFSMKF 589
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 38679954    623 VPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 702
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38679954    703 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 777
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 38679954 608 FGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKLY 687
Cdd:cd04403   1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 688 FRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTL 767
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                       170       180       190
                ....*....|....*....|....*....|....*
gi 38679954 768 LRPsEVESkahltsaADIWSHDVMaQVQVLLYYLQ 802
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 38679954 608 FGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDAN-NKDILLMLSDMDINAIAGTLKL 686
Cdd:cd04372   1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 687 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 766
Cdd:cd04372  81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 38679954 767 LLRPSEVESKAHLtsaadiwsHDVMAQVQVLLYYLQHPPISF 808
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 38679954 607 VFGVKI-SVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAvfDANNKDILLMLSD---MDINAIAG 682
Cdd:cd04395   1 TFGVPLdDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQE--ELNRGGFDIDLQDprwRDVNVVSS 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 683 TLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATV 762
Cdd:cd04395  79 LLKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIV 158

                       170
                ....*....|
gi 38679954 763 FGPTLLRPSE 772
Cdd:cd04395 159 FGPTLVRTSD 168

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 38679954  55 RKLVLSGFLASEEIYINQLEALLLP-MKPLKATATTsqpvLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVT 132
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVfLKPLDKELLP----LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDkSGPR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 133 MGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKvkgpkdskDSHTSVTMEALLYKPIDRVTRSTLV 212
Cdd:cd00160  77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAE--------SECGRLKLESLLLKPVQRLTKYPLL 148

                       170       180       190
                ....*....|....*....|....*....|...
gi 38679954 213 LHDLLKHTPVDHPDYPLLQDALRISQNFLSSIN 245
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 38679954     58 VLSGFLASEEIYINQLEALL-LPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGH 135
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVeVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954    136 LFQKLASQLGVYKAFVDNYKVALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHD 215
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKE 149

                          170       180       190
                   ....*....|....*....|....*....|.
gi 38679954    216 LLKHTPVDHPDYPLLQDALRISQNFLSSINE 246
Cdd:smart00325 150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 180

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 38679954 607 VFGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEvGIYRISGVATDIQALKAVFDANN-KDILLMLSDMDINAIAGTLK 685
Cdd:cd04384   2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQiPDLTKDVYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 686 LYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGP 765
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 38679954 766 TLLRPSEVESKAHLTSAADIwshDVMAQVQVLLYYLQH 803
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 38679954 607 VFGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKL 686
Cdd:cd04386   4 VFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFYSDPHAVASALKS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 687 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 766
Cdd:cd04386  84 YLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPN 163

                       170
                ....*....|.
gi 38679954 767 LLRPSEVESKA 777
Cdd:cd04386 164 LLWAKNEGSLA 174

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38679954 626 IVRQCVEEVEKRGIEEVGIYRISGVATDIQAL-KAVFD---ANNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLY 701
Cdd:cd04374  31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLlSLGLDpktSTPGDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYELH 110

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38679954 702 PAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSE 772
Cdd:cd04374 111 NDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQE 181

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP 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 38679954 608 FGVKISVVTKrERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDIllMLSDMDINAIAGTLKLY 687
Cdd:cd04377   1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSV--NLEDYPIHVITSVLKQW 77