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 1191879724 307 LGRLRGFEGKLTAQGKLLGQDTFWVTEPEAGglLSSRGRERRVFLFEQIVIFSEALGGGvRGGTQPGYVYKSSIKVSCLG 386
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAG--LLQKGKERRVFLFEQIIIFSEILGKK-TQFSNPGYIYKNHIKVNKMS 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1191879724 387 LEGNLQGDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQILESQRDFLNALQSPIEY 449
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 1191879724 307 LGRLRGFEGKLTAQGKLLGQDTFWVTEPEAGglLSSRGRERRVFLFEQIVIFSEALGGGvRGGTQPGYVYKSSIKVSCLG 386
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAG--LLQKGKERRVFLFEQIIIFSEILGKK-TQFSNPGYIYKNHIKVNKMS 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1191879724 387 LEGNLQGDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQILESQRDFLNALQSPIEY 449
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 1191879724 131 YVLSELVETEKMYVDDLGQIVEGYMATMAAQGVPENLRGRDRIvFGNIQQIYEWHRDyFLQELQRCLKDPDW----LAQL 206
Cdd:cd00160     3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELL-FGNIEEIYEFHRI-FLKSLEERVEEWDKsgprIGDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191879724 207 FIKHERRLHMYVVYCQNKPKSEHVVSEF--GDSYFEELRQQLG---HRLQLNDLLIKPVQRIMKYQLLLKDFLKYYSRAG 281
Cdd:cd00160    81 FLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDGH 160

                         170       180
                  ....*....|....*....|.
gi 1191879724 282 MDTEELEQAVEVMCFVPKRCN 302
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 1191879724  109 ETLSQASENEEEQKKKALERSMyVLSELVETEKMYVDDLGQIVEGYMATMAAQGV-PENLRGR-DRIVFGNIQQIYEWHR 186
Cdd:COG5422    466 WTLSVPKEVWESLPKQEIKRQE-AIYEVIYTERDFVKDLEYLRDTWIKPLEESNIiPENARRNfIKHVFANINEIYAVNS 544

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191879724  187 DYF--LQELQRCLKDPDWLAQLFIKHERRLHMYVVYCQNKP-------KSEHVVSEFG--DSYFEELRQQLghRLQLNDL 255
Cdd:COG5422    545 KLLkaLTNRQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPyakyefeREKSVNPNFArfDHEVERLDESR--KLELDGY 622

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1191879724  256 LIKPVQRIMKYQLLLKDFLKYYSRAGMDTEELEQAVEVM 294
Cdd:COG5422    623 LTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDML 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 1191879724 307 LGRLRGFEGKLTAQGKLLGQDTFWVTEPEAGglLSSRGRERRVFLFEQIVIFSEALGGGvRGGTQPGYVYKSSIKVSCLG 386
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAG--LLQKGKERRVFLFEQIIIFSEILGKK-TQFSNPGYIYKNHIKVNKMS 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1191879724 387 LEGNLQGDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQILESQRDFLNALQSPIEY 449
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 1191879724 131 YVLSELVETEKMYVDDLGQIVEGYMATMAAQGVPENLRGRDRIvFGNIQQIYEWHRDyFLQELQRCLKDPDW----LAQL 206
Cdd:cd00160     3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELL-FGNIEEIYEFHRI-FLKSLEERVEEWDKsgprIGDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191879724 207 FIKHERRLHMYVVYCQNKPKSEHVVSEF--GDSYFEELRQQLG---HRLQLNDLLIKPVQRIMKYQLLLKDFLKYYSRAG 281
Cdd:cd00160    81 FLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDGH 160

                         170       180
                  ....*....|....*....|.
gi 1191879724 282 MDTEELEQAVEVMCFVPKRCN 302
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 1191879724 302 NDMMTLGRLRGFEGKLTAQGKLLGQDTFWVTEpeaggllSSRGRERRVFLFEQIVIFSEAlgggvrGGTQPG---YVYKS 378
Cdd:cd13242     8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQ-------GRKKCLRHVFLFEDLILFSKP------KKTPGGkdvYIYKH 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1191879724 379 SIKVSCLGLEGNLQGDPCRFALTSRGPEGGiQRYVLQTADPAVSQAWIKQVAQILESQ 436
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 1191879724 312 GFEGKLTAQGKLLGQDTFWV-TEPEAG---GLLSSRGRERRVFLFEQIVIFSEALGggvRGGTQPGYVYKSSIKVSCLGL 387
Cdd:cd01227     4 GYDGNLGDLGKLLMQGSFNVwTEHKKGhtkKLARFKPMQRHIFLYEKAVLFCKKRG---ENGEAPSYSYKNSLNTTAVGL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1191879724 388 EGNLQGDPCRFALTSRGPEggiQRYVLQTADPAVSQAWIKQVAQILESQ 436
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 1191879724 313 FEGKLTAQGKLLGQDTFWVTEPEAGGLLSSRGRERRVFLFEQIVIFSEaLGGGVRGGTQpGYVYKSSIKVSCLGLEGNLQ 392
Cdd:cd13239     5 YPAPLQALGEPIRQGHFTVWEEAPEVKTSSRGHHRHVFLFKNCVVICK-PKRDSRTDTV-TYVFKNKMKLSDIDVKDTVE 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1191879724 393 GDPCRFALTSRgPEGGIQRYVLQTADPAVSQAWIKQVAQI 432
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 1191879724 315 GKLtaqGKLLGQDTFWVTEPEaggllsSRGRERRVFLFEQIVIFSEalgggVRGGTQPGYVY--KSSIKVSCLGLEgNLQ 392
Cdd:cd13325     4 HKL---GRLLRHDWFTVTDGE------GKAKERYLFLFKSRILITK-----VRRISEDRSVFilKDIIRLPEVNVK-QHP 68

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1191879724 393 GDPCRFALTSRGPEGGIQRYVLQTADPAVSQAWIKQVAQ 431
Cdd:cd13325    69 DDERTFELQPKLPAFGILPIDFKAHKDEIKDYWLNEIEE 107