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 84794546  272 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWEGPDLTSYGELVLEGTFRIQKAKKERTLFLLDQLLLITK 351
Cdd:cd13243    1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 84794546  352 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 417
Cdd:cd13243   81 KREDgILQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 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 84794546  272 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWEGPDLTSYGELVLEGTFRIQKAKKERTLFLLDQLLLITK 351
Cdd:cd13243    1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 84794546  352 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 417
Cdd:cd13243   81 KREDgILQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 84794546  114 DRVVQEILETERTYVQDLKSIVEGYLECIrDQTKLPLVTEDRAALFGNIQDIYHFNSELLQDLENC----ENDPVAIAEC 189
Cdd:cd00160    2 QEVIKELLQTERNYVRDLKLLVEVFLKPL-DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewDKSGPRIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84794546  190 FVSKSEEFHIYTQYCTNYPRSVAVLTECMRNKilTKF--FRERQETLRHSLPLGSYLLKPVQRILKYHLLLHEIENHLDK 267
Cdd:cd00160   81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFN--KFFqeFLEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                        170       180
                 ....*....|....*....|...
gi 84794546  268 ATEGYDVVLDAIDTMQRVAWHIN 290
Cdd:cd00160  159 GHEDREDLKKALEAIKEVASQVN 181

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84794546   75 PQNMNGVSEKQ--PRTPWrmdTSGTPQTTADSATSPKLLYVDrVVQEILETERTYVQDLksivegylECIRDQTKLPLVT 152
Cdd:COG5422  449 KRNSSLALDKFdeEKNLW---TLSVPKEVWESLPKQEIKRQE-AIYEVIYTERDFVKDL--------EYLRDTWIKPLEE 516

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84794546  153 EDRAA----------LFGNIQDIYHFNSELLQDLENCEN-DPVA--IAECFVSKSEEFHIYTQYCTNYPRSVAVLTEcmR 219
Cdd:COG5422  517 SNIIPenarrnfikhVFANINEIYAVNSKLLKALTNRQClSPIVngIADIFLDYVPKFEPFIKYGASQPYAKYEFER--E 594

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 84794546  220 NKILTKFFRERQETLRHSLP----LGSYLLKPVQRILKYHLLLHEIENHLDKATEGYDVVLDAID 280
Cdd:COG5422  595 KSVNPNFARFDHEVERLDESrkleLDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVID 659

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 84794546  272 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWEGPDLTSYGELVLEGTFRIQKAKKERTLFLLDQLLLITK 351
Cdd:cd13243    1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 84794546  352 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 417
Cdd:cd13243   81 KREDgILQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 84794546  114 DRVVQEILETERTYVQDLKSIVEGYLECIrDQTKLPLVTEDRAALFGNIQDIYHFNSELLQDLENC----ENDPVAIAEC 189
Cdd:cd00160    2 QEVIKELLQTERNYVRDLKLLVEVFLKPL-DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewDKSGPRIGDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 84794546  190 FVSKSEEFHIYTQYCTNYPRSVAVLTECMRNKilTKF--FRERQETLRHSLPLGSYLLKPVQRILKYHLLLHEIENHLDK 267
Cdd:cd00160   81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFN--KFFqeFLEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                        170       180
                 ....*....|....*....|...
gi 84794546  268 ATEGYDVVLDAIDTMQRVAWHIN 290
Cdd:cd00160  159 GHEDREDLKKALEAIKEVASQVN 181

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 84794546  356 TFTYKAHILCGNLMLVEVIPKEPLSFsVFHYKNPKLQH---TVQAKSQQDKRLWVLHLKRlILEN 417
Cdd:cd13241   64 GYIYKNHIKVNKMSLEENVDGDPLRF-ALKSRDPNNPSetfILQAASPEVRQEWVDTINQ-ILDT 126