Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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 1831517999 386 LIQVKRAHEVMTSQAARINDEKKKAEHIERVGQLQSTLQKWKADEiqisnLSAYGDLLLEATFRQAGSKTTRLLFLFEEM 465
Cdd:cd13243     1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPE-----LTTYGDLVLEGTFRMAGAKNERLLFLFDKM 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1831517999 466 LLIVKQR-GANYVCKDYIMCSNLMLNEWIcPEEPLSFQVLSFDNPRAQYVFMASSMEQKRTWMQELKRMMLDH 537
Cdd:cd13243    76 LLITKKReDGILQYKTHIMCSNLMLSESI-PKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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 1831517999 386 LIQVKRAHEVMTSQAARINDEKKKAEHIERVGQLQSTLQKWKADEiqisnLSAYGDLLLEATFRQAGSKTTRLLFLFEEM 465
Cdd:cd13243     1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPE-----LTTYGDLVLEGTFRMAGAKNERLLFLFDKM 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1831517999 466 LLIVKQR-GANYVCKDYIMCSNLMLNEWIcPEEPLSFQVLSFDNPRAQYVFMASSMEQKRTWMQELKRMMLDH 537
Cdd:cd13243    76 LLITKKReDGILQYKTHIMCSNLMLSESI-PKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 1831517999  227 IAIELLDTERTYVEDLNAVIKGYMDFLVEDREKLkvTLDAISSLFGCIERIFAFNKQLYNQL----DAADLDCVKMSRCF 302
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLL--SPNELETLFGNIEEIYEFHRDFLDELeeriEEWDDSVERIGDVF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831517999  303 VESSGKFEDYIEYCTNYHRMMSTLYHLQQQPLVARALQERQLALNH-SLQLSAYLLKPVQRILKYHLFLENILKNMPStt 381
Cdd:smart00325  79 LKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHTPE-- 156

                          170       180
                   ....*....|....*....|....
gi 1831517999  382 HPEELIQVKRAHEVMTSQAARIND 405
Cdd:smart00325 157 DHEDREDLKKALKAIKELANQVNE 180

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1831517999  470 KQRGANYVCKDYIMCSNLMLNEWICP---EEPLSFQVLSFDnpRAQYVFMASSMEQKRTWMQELKRMM 534
Cdd:smart00233  36 KKDKKSYKPKGSIDLSGCTVREAPDPdssKKPHCFEIKTSD--RKTLLLQAESEEEREKWVEALRKAI 101

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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 1831517999 386 LIQVKRAHEVMTSQAARINDEKKKAEHIERVGQLQSTLQKWKADEiqisnLSAYGDLLLEATFRQAGSKTTRLLFLFEEM 465
Cdd:cd13243     1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPE-----LTTYGDLVLEGTFRMAGAKNERLLFLFDKM 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1831517999 466 LLIVKQR-GANYVCKDYIMCSNLMLNEWIcPEEPLSFQVLSFDNPRAQYVFMASSMEQKRTWMQELKRMMLDH 537
Cdd:cd13243    76 LLITKKReDGILQYKTHIMCSNLMLSESI-PKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 1831517999  227 IAIELLDTERTYVEDLNAVIKGYMDFLVEDREKLkvTLDAISSLFGCIERIFAFNKQLYNQL----DAADLDCVKMSRCF 302
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLL--SPNELETLFGNIEEIYEFHRDFLDELeeriEEWDDSVERIGDVF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831517999  303 VESSGKFEDYIEYCTNYHRMMSTLYHLQQQPLVARALQERQLALNH-SLQLSAYLLKPVQRILKYHLFLENILKNMPStt 381
Cdd:smart00325  79 LKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHTPE-- 156

                          170       180
                   ....*....|....*....|....
gi 1831517999  382 HPEELIQVKRAHEVMTSQAARIND 405
Cdd:smart00325 157 DHEDREDLKKALKAIKELANQVNE 180

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1831517999 475 NYVCKDYIMCSNLMLNEwICPEEPLSFQVLSFD--NPRAQYVFMASSMEQKRTWMQELKRMM 534
Cdd:cd13241    64 GYIYKNHIKVNKMSLEE-NVDGDPLRFALKSRDpnNPSETFILQAASPEVRQEWVDTINQIL 124