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 568964668  312 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWEGPDLTSYGELVLEGTFRIQKAKKERTLFLLDQLLLITK 391
Cdd:cd13243     1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568964668  392 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 457
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 568964668  312 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWEGPDLTSYGELVLEGTFRIQKAKKERTLFLLDQLLLITK 391
Cdd:cd13243     1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568964668  392 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 457
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 568964668  154 DRVVQEILETERTYVQDLKSIVEGYLECIrDQTKLPLVTEDRAALFGNIQDIYHFNSELLQDLENC----ENDPVAIAEC 229
Cdd:cd00160     2 QEVIKELLQTERNYVRDLKLLVEVFLKPL-DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewDKSGPRIGDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568964668  230 FVSKSEEFHIYTQYCTNYPRSVAVLTECMRNKilTKF--FRERQETLRHSLPLGSYLLKPVQRILKYHLLLHEIENHLDK 307
Cdd:cd00160    81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFN--KFFqeFLEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                         170       180
                  ....*....|....*....|...
gi 568964668  308 ATEGYDVVLDAIDTMQRVAWHIN 330
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 568964668  115 PQNMNGVSEKQ--PRTPWrmdTSGTPQTTADSATSPKLLYVDrVVQEILETERTYVQDLksivegylECIRDQTKLPLVT 192
Cdd:COG5422   449 KRNSSLALDKFdeEKNLW---TLSVPKEVWESLPKQEIKRQE-AIYEVIYTERDFVKDL--------EYLRDTWIKPLEE 516

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568964668  193 EDRAA----------LFGNIQDIYHFNSELLQDLENCEN-DPVA--IAECFVSKSEEFHIYTQYCTNYPRSVAVLTEcmR 259
Cdd:COG5422   517 SNIIPenarrnfikhVFANINEIYAVNSKLLKALTNRQClSPIVngIADIFLDYVPKFEPFIKYGASQPYAKYEFER--E 594

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568964668  260 NKILTKFFRERQETLRHSLP----LGSYLLKPVQRILKYHLLLHEIENHLDKATEGYDVVLDAID 320
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 568964668  312 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWEGPDLTSYGELVLEGTFRIQKAKKERTLFLLDQLLLITK 391
Cdd:cd13243     1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568964668  392 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 457
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 568964668  154 DRVVQEILETERTYVQDLKSIVEGYLECIrDQTKLPLVTEDRAALFGNIQDIYHFNSELLQDLENC----ENDPVAIAEC 229
Cdd:cd00160     2 QEVIKELLQTERNYVRDLKLLVEVFLKPL-DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewDKSGPRIGDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568964668  230 FVSKSEEFHIYTQYCTNYPRSVAVLTECMRNKilTKF--FRERQETLRHSLPLGSYLLKPVQRILKYHLLLHEIENHLDK 307
Cdd:cd00160    81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFN--KFFqeFLEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                         170       180
                  ....*....|....*....|...
gi 568964668  308 ATEGYDVVLDAIDTMQRVAWHIN 330
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 568964668  396 TFTYKAHILCGNLMLVEVIPKEPLSFsVFHYKNPKLQH---TVQAKSQQDKRLWVLHLKRlILEN 457
Cdd:cd13241    64 GYIYKNHIKVNKMSLEENVDGDPLRF-ALKSRDPNNPSetfILQAASPEVRQEWVDTINQ-ILDT 126