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 1048560303  332 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWKGPDLTSYGELVLEGTFRIQRAKNERTLFLFDKLLLITK 411
Cdd:cd13243      1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1048560303  412 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 477
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 1048560303  332 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWKGPDLTSYGELVLEGTFRIQRAKNERTLFLFDKLLLITK 411
Cdd:cd13243      1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1048560303  412 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 477
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 1048560303  174 DRVVQEILETERTYVQDLKSIVEDYLDCIrDQTKLPLGTEERSALFGNIQDIYHFNSELLQDLENC----ENDPVAIAEC 249
Cdd:cd00160      2 QEVIKELLQTERNYVRDLKLLVEVFLKPL-DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewDKSGPRIGDV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1048560303  250 FVSKSEEFHIYTQYCTNYPRSVAVLTECMRNKilaKFFRE---RQETLKHSLPLGSYLLKPVQRILKYHLLLHEIENHLD 326
Cdd:cd00160     81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFN---KFFQEfleKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157

                          170       180
                   ....*....|....*....|....
gi 1048560303  327 KDTEGYDVVLDAIDTMQRVAWHIN 350
Cdd:cd00160    158 DGHEDREDLKKALEAIKEVASQVN 181

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        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1048560303   383 LVLEGTFRIQRAKN-----ERTLFLFDKLLLITKKRDDT--FTYKAHILCGNLMLVEV----IPKEPLSFSVFHykNPKL 451
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKksYKPKGSIDLSGCTVREApdpdSSKKPHCFEIKT--SDRK 78

                            90       100
                    ....*....|....*....|...
gi 1048560303   452 QHTVQAKSQQDKRLWVLHLKRLI 474
Cdd:smart00233   79 TLLLQAESEEEREKWVEALRKAI 101

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1048560303  381 GELVLEGTFRIQRAKnERTLFLFDKLLLITKKRDDT--FTYKAHILCGNLMLVEVI----PKEPLSFSV-FHYKNPKLQH 453
Cdd:pfam00169    5 GWLLKKGGGKKKSWK-KRYFVLFDGSLLYYKDDKSGksKEPKGSISLSGCEVVEVVasdsPKRKFCFELrTGERTGKRTY 83

                           90       100
                   ....*....|....*....|.
gi 1048560303  454 TVQAKSQQDKRLWVLHLKRLI 474
Cdd:pfam00169   84 LLQAESEEERKDWIKAIQSAI 104

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 1048560303  332 YDVVLDAIDTMQRVAWHINDMKRKHEHAVRLQEIQSLLTNWKGPDLTSYGELVLEGTFRIQRAKNERTLFLFDKLLLITK 411
Cdd:cd13243      1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1048560303  412 KRDD-TFTYKAHILCGNLMLVEVIPKEPLSFSVFHYKNPKLQHTVQAKSQQDKRLWVLHLKRLILEN 477
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 1048560303  174 DRVVQEILETERTYVQDLKSIVEDYLDCIrDQTKLPLGTEERSALFGNIQDIYHFNSELLQDLENC----ENDPVAIAEC 249
Cdd:cd00160      2 QEVIKELLQTERNYVRDLKLLVEVFLKPL-DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewDKSGPRIGDV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1048560303  250 FVSKSEEFHIYTQYCTNYPRSVAVLTECMRNKilaKFFRE---RQETLKHSLPLGSYLLKPVQRILKYHLLLHEIENHLD 326
Cdd:cd00160     81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFN---KFFQEfleKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157

                          170       180
                   ....*....|....*....|....
gi 1048560303  327 KDTEGYDVVLDAIDTMQRVAWHIN 350
Cdd:cd00160    158 DGHEDREDLKKALEAIKEVASQVN 181

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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 1048560303  357 EHAVRLQEIQSLLTNWKGPDL--TSYgELVLEGTF-RIQRAKN-ERTLFLFDKLLLITKK---RDDTFTYKAHILCgNLM 429
Cdd:cd01224      2 ENLEKLAAWQSTVEGWEGEDLsdRSS-ELIHSGELtKISAGRAqERTFFLFDHQLVYCKKdllRRKNYIYKGRIDT-DNM 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1048560303  430 LVEVIPKEPLSFSVFHYKNP-KLQ-------HTVQAKSQQDKRLWVLHLKR 472
Cdd:cd01224     80 EIEDLPDGKDDESGVTVKNAwKIYnasknkwYVLCAKSAEEKQRWLEAFAE 130

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 1048560303  377 LTSYGELVLEGTF--------RIQRAKnERTLFLFDKLL----LITKKR---DDTFTYKAHILCGNLMLVEVIPKEPLSF 441
Cdd:cd13241     11 ITAQGKLLLQGTLlvsepsagLLQKGK-ERRVFLFEQIIifseILGKKTqfsNPGYIYKNHIKVNKMSLEENVDGDPLRF 89

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1048560303  442 sVFHYKNPKLQH---TVQAKSQQDKRLWVLHLKRlILEN 477
Cdd:cd13241     90 -ALKSRDPNNPSetfILQAASPEVRQEWVDTINQ-ILDT 126

Shape and Conjugation Deficiency 1 Pleckstrin homology (PH) domain; Fission yeast Scd1 is an exchange factor for Cdc42 and an effector of Ras1, the homolog of the human H-Ras. Scd2/Bem1 mediates Cdc42 activation by binding to Scd1/Cdc24 and to Cdc42. Ras1 regulates Scd1/Cdc24/Ral1, which is a putative guanine nucleotide exchange factor for Cdc42, a member of the Rho family of Ras-like proteins. Cdc42 then activates the Shk1/Orb2 protein kinase. Scd1 interacts with Klp5 and Klp6 kinesins to mediate cytokinesis. 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 1048560303  353 KRKHEHAVRLQEIQSLLTNWKGPDLTSYGELVLEGTFRIQRAKNER--TLFLFDKLLLITK 411
Cdd:cd13246      1 QRRAENQQVVDDLKARVEDWKGHSLDSFGELLLHDTFTVRKDDSEReyHVYLFERILLCCK 61

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        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1048560303   383 LVLEGTFRIQRAKN-----ERTLFLFDKLLLITKKRDDT--FTYKAHILCGNLMLVEV----IPKEPLSFSVFHykNPKL 451
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKksYKPKGSIDLSGCTVREApdpdSSKKPHCFEIKT--SDRK 78

                            90       100
                    ....*....|....*....|...
gi 1048560303   452 QHTVQAKSQQDKRLWVLHLKRLI 474
Cdd:smart00233   79 TLLLQAESEEEREKWVEALRKAI 101

Pleckstrin homology (PH) domain; 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 1048560303  381 GELVLEGTFRIQRAKnERTLFLFDKLLLITK-KRDDTFTYKAHI-LCGNLMLVEVIPKE-PLSFSVFHYKNPKlqHTVQA 457
Cdd:cd00821      3 GYLLKRGGGGLKSWK-KRWFVLFEGVLLYYKsKKDSSYKPKGSIpLSGILEVEEVSPKErPHCFELVTPDGRT--YYLQA 79

                           90
                   ....*....|...
gi 1048560303  458 KSQQDKRLWVLHL 470
Cdd:cd00821     80 DSEEERQEWLKAL 92

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1048560303  381 GELVLEGTFRIQRAKnERTLFLFDKLLLITKKRDDT--FTYKAHILCGNLMLVEVI----PKEPLSFSV-FHYKNPKLQH 453
Cdd:pfam00169    5 GWLLKKGGGKKKSWK-KRYFVLFDGSLLYYKDDKSGksKEPKGSISLSGCEVVEVVasdsPKRKFCFELrTGERTGKRTY 83

                           90       100
                   ....*....|....*....|.
gi 1048560303  454 TVQAKSQQDKRLWVLHLKRLI 474
Cdd:pfam00169   84 LLQAESEEERKDWIKAIQSAI 104