p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 311255796 339 LGRLRGFEGKLTAQGKLLGQDTFWVTEPEAGglLSSRGRERRVFLFEQIVIFSEALGGGvRGGTQPGYVYKSSIKVSCLG 418
Cdd:cd13241    1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAG--LLQKGKERRVFLFEQIIIFSEILGKK-TQFSNPGYIYKNHIKVNKMS 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 311255796 419 LEGNLQGDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQILESQRDFLNALQSPIEY 481
Cdd:cd13241   78 LEENVDGDPLRFALKSRDPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 311255796 339 LGRLRGFEGKLTAQGKLLGQDTFWVTEPEAGglLSSRGRERRVFLFEQIVIFSEALGGGvRGGTQPGYVYKSSIKVSCLG 418
Cdd:cd13241    1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAG--LLQKGKERRVFLFEQIIIFSEILGKK-TQFSNPGYIYKNHIKVNKMS 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 311255796 419 LEGNLQGDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQILESQRDFLNALQSPIEY 481
Cdd:cd13241   78 LEENVDGDPLRFALKSRDPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

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 311255796 163 YVLSELVETEKMYVDDLGQIVEGYMATMAAQGVPENLRGRDRIvFGNIQQIYEWHRDyFLQELQRCLKDPDW----LAQL 238
Cdd:cd00160    3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELL-FGNIEEIYEFHRI-FLKSLEERVEEWDKsgprIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311255796 239 FIKHERRLHMYVVYCQNKPKSEHVVSEF--GDSYFEELRQQLG---HRLQLNDLLIKPVQRIMKYQLLLKDFLKYYSRAG 313
Cdd:cd00160   81 FLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDGH 160

                        170       180
                 ....*....|....*....|.
gi 311255796 314 MDTEELEQAVEVMCFVPKRCN 334
Cdd:cd00160  161 EDREDLKKALEAIKEVASQVN 181

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311255796  132 QDKTQPPEEETLSQA-SENEEEQKKKALErsmyVLSELVETEKMYVDDLGQIVEGYMATMAAQGV-PENLRGR-DRIVFG 208
Cdd:COG5422   459 FDEEKNLWTLSVPKEvWESLPKQEIKRQE----AIYEVIYTERDFVKDLEYLRDTWIKPLEESNIiPENARRNfIKHVFA 534

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311255796  209 NIQQIYEWHRDYF--LQELQRCLKDPDWLAQLFIKHERRLHMYVVYCQNKP-------KSEHVVSEFG--DSYFEELRQQ 277
Cdd:COG5422   535 NINEIYAVNSKLLkaLTNRQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPyakyefeREKSVNPNFArfDHEVERLDES 614

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 311255796  278 LghRLQLNDLLIKPVQRIMKYQLLLKDFLKYYSRAGMDTEELEQAVEVM 326
Cdd:COG5422   615 R--KLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDML 661

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 311255796 339 LGRLRGFEGKLTAQGKLLGQDTFWVTEPEAGglLSSRGRERRVFLFEQIVIFSEALGGGvRGGTQPGYVYKSSIKVSCLG 418
Cdd:cd13241    1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAG--LLQKGKERRVFLFEQIIIFSEILGKK-TQFSNPGYIYKNHIKVNKMS 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 311255796 419 LEGNLQGDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQILESQRDFLNALQSPIEY 481
Cdd:cd13241   78 LEENVDGDPLRFALKSRDPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

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 311255796 163 YVLSELVETEKMYVDDLGQIVEGYMATMAAQGVPENLRGRDRIvFGNIQQIYEWHRDyFLQELQRCLKDPDW----LAQL 238
Cdd:cd00160    3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELL-FGNIEEIYEFHRI-FLKSLEERVEEWDKsgprIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 311255796 239 FIKHERRLHMYVVYCQNKPKSEHVVSEF--GDSYFEELRQQLG---HRLQLNDLLIKPVQRIMKYQLLLKDFLKYYSRAG 313
Cdd:cd00160   81 FLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDGH 160

                        170       180
                 ....*....|....*....|.
gi 311255796 314 MDTEELEQAVEVMCFVPKRCN 334
Cdd:cd00160  161 EDREDLKKALEAIKEVASQVN 181

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 311255796 334 NDMMTLGRLRGFEGKLTAQGKLLGQDTFWVTEpeaggllSSRGRERRVFLFEQIVIFSEAlgggvrGGTQPG---YVYKS 410
Cdd:cd13242    8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQ-------GRKKCLRHVFLFEDLILFSKP------KKTPGGkdvYIYKH 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 311255796 411 SIKVSCLGLEGNLQGDPCRFALTSRGPEGGiQRYVLQTADPAVSQAWIKQVAQILESQ 468
Cdd:cd13242   75 SIKTSDIGLTENVGDSGLKFEIWFRRRKAR-DTYILQATSPEIKQAWTSDIAKLLWKQ 131

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. 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 311255796 344 GFEGKLTAQGKLLGQDTFWV-TEPEAG---GLLSSRGRERRVFLFEQIVIFSEALGggvRGGTQPGYVYKSSIKVSCLGL 419
Cdd:cd01227    4 GYDGNLGDLGKLLMQGSFNVwTEHKKGhtkKLARFKPMQRHIFLYEKAVLFCKKRG---ENGEAPSYSYKNSLNTTAVGL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 311255796 420 EGNLQGDPCRFALTSRGPEggiQRYVLQTADPAVSQAWIKQVAQILESQ 468
Cdd:cd01227   81 TENVKGDTKKFEIWLNGRE---EVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart 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 311255796 345 FEGKLTAQGKLLGQDTFWVTEPEAGGLLSSRGRERRVFLFEQIVIFSEaLGGGVRGGTQpGYVYKSSIKVSCLGLEGNLQ 424
Cdd:cd13239    5 YPAPLQALGEPIRQGHFTVWEEAPEVKTSSRGHHRHVFLFKNCVVICK-PKRDSRTDTV-TYVFKNKMKLSDIDVKDTVE 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 311255796 425 GDPCRFALTSRgPEGGIQRYVLQTADPAVSQAWIKQVAQI 464
Cdd:cd13239   83 GDDRSFGLWHE-HRGSVRKYTLQARSAIIKSSWLKDLRDL 121

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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 311255796 347 GKLtaqGKLLGQDTFWVTEPEaggllsSRGRERRVFLFEQIVIFSEalgggVRGGTQPGYVY--KSSIKVSCLGLEgNLQ 424
Cdd:cd13325    4 HKL---GRLLRHDWFTVTDGE------GKAKERYLFLFKSRILITK-----VRRISEDRSVFilKDIIRLPEVNVK-QHP 68

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 311255796 425 GDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQ 463
Cdd:cd13325   69 DDERTFELQPKLPAFGILPIDFKAHKDEIKDYWLNEIEE 107