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 1039751490 378 LGRLQGFEGTLTAQGKLLQQDTFYVIELDAGMQSRTKERRVFLFEQIVIFSELLRKGS--LTPGYMFKRSIKMNYLVLED 455
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTqfSNPGYIYKNHIKVNKMSLEE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 456 NVDGDPCKFALMNRE---TSERVILQAANSDIQQAWVQDINQVLETQRDFLNALQSPIEY 512
Cdd:cd13241    81 NVDGDPLRFALKSRDpnnPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039751490 595 TMTVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11853     1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVL 57

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 1039751490 378 LGRLQGFEGTLTAQGKLLQQDTFYVIELDAGMQSRTKERRVFLFEQIVIFSELLRKGS--LTPGYMFKRSIKMNYLVLED 455
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTqfSNPGYIYKNHIKVNKMSLEE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 456 NVDGDPCKFALMNRE---TSERVILQAANSDIQQAWVQDINQVLETQRDFLNALQSPIEY 512
Cdd:cd13241    81 NVDGDPLRFALKSRDpnnPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 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 1039751490 201 RMFVLNELVQTEKDYVKDLGIVVEGFMKRIEEKGVPeDMRGKEKIVFGNIHQIYDWHKDFfLAELEKCIQEQD----RLA 276
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFHRIF-LKSLEERVEEWDksgpRIG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 277 QLFIKHERKLHIYVWYCQNKPRSEYIVAEYDA---YFEEVKQEIN---QRLTLSDFLIKPIQRITKYQLLLKDFLRYSEK 350
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnkFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                         170       180
                  ....*....|....*....|...
gi 1039751490 351 AGLECSDIEKAVELMCLVPKRCN 373
Cdd:cd00160   159 GHEDREDLKKALEAIKEVASQVN 181

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039751490 595 TMTVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11853     1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVL 57

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  192 EQKAKALRGRMFVLNELVQTEKDYVKDLGIVVEGFMKRIEE-KGVPEDMRGK-EKIVFGNIHQIYDWHKDFF--LAELEK 267
Cdd:COG5422    476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEEsNIIPENARRNfIKHVFANINEIYAVNSKLLkaLTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  268 CIQEQDRLAQLFIKHERKLHIYVWYCQNKPRSEYI----------VAEYDAYFEEVKQeiNQRLTLSDFLIKPIQRITKY 337
Cdd:COG5422    556 LSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEfereksvnpnFARFDHEVERLDE--SRKLELDGYLTKPTTRLARY 633

                          170       180
                   ....*....|....*....|....*...
gi 1039751490  338 QLLLKDFLRYSEKAGLECSDIEKAVELM 365
Cdd:COG5422    634 PLLLEEVLKFTDPDNPDTEDIPKVIDML 661

PH domain; This entry contains a PH domain found in RhoGEF proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 385 EGTLTAQGKLLQQDTFYVIEL-DAGMQSRTKERRVFLFEQIVIFSELLRKGS-------LTPGYMFKRSI 446
Cdd:pfam19057   4 KLLSSGQRYLIRQDDVVETVYnERGEVLKSKERRLFLLNDLLVCVTVNSKSGsdfgslpGGEKYKLKWSV 73

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 1039751490 378 LGRLQGFEGTLTAQGKLLQQDTFYVIELDAGMQSRTKERRVFLFEQIVIFSELLRKGS--LTPGYMFKRSIKMNYLVLED 455
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTqfSNPGYIYKNHIKVNKMSLEE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 456 NVDGDPCKFALMNRE---TSERVILQAANSDIQQAWVQDINQVLETQRDFLNALQSPIEY 512
Cdd:cd13241    81 NVDGDPLRFALKSRDpnnPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 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 1039751490 201 RMFVLNELVQTEKDYVKDLGIVVEGFMKRIEEKGVPeDMRGKEKIVFGNIHQIYDWHKDFfLAELEKCIQEQD----RLA 276
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFHRIF-LKSLEERVEEWDksgpRIG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 277 QLFIKHERKLHIYVWYCQNKPRSEYIVAEYDA---YFEEVKQEIN---QRLTLSDFLIKPIQRITKYQLLLKDFLRYSEK 350
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnkFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                         170       180
                  ....*....|....*....|...
gi 1039751490 351 AGLECSDIEKAVELMCLVPKRCN 373
Cdd:cd00160   159 GHEDREDLKKALEAIKEVASQVN 181

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039751490 595 TMTVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11853     1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVL 57

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 1039751490 373 NDMMNLGRLQGFEGTLTAQGKLLQQDTFYVIeldagmQSRTK-ERRVFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYL 451
Cdd:cd13242     8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVW------QGRKKcLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSDI 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039751490 452 VLEDNVDGDPCKFAL--MNRETSERVILQAANSDIQQAWVQDINQVLETQ 499
Cdd:cd13242    82 GLTENVGDSGLKFEIwfRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQ 131

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 381 LQGFEGTLTAQGKLLQQDTFYVIELDAgMQSRTKERRVFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYLVLEDNVDGD 460
Cdd:cd13240     2 LEGCDEDLDSLGEVILQDSFQVWDPKQ-LIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039751490 461 PCKFALMNRE--TSE-RVILQAANSDIQQAWVQDINQVLE 497
Cdd:cd13240    81 PCKFALWTGRvpTSDnKIVLKASSLEVKQTWVKKLREVIQ 120

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  192 EQKAKALRGRMFVLNELVQTEKDYVKDLGIVVEGFMKRIEE-KGVPEDMRGK-EKIVFGNIHQIYDWHKDFF--LAELEK 267
Cdd:COG5422    476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEEsNIIPENARRNfIKHVFANINEIYAVNSKLLkaLTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  268 CIQEQDRLAQLFIKHERKLHIYVWYCQNKPRSEYI----------VAEYDAYFEEVKQeiNQRLTLSDFLIKPIQRITKY 337
Cdd:COG5422    556 LSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEfereksvnpnFARFDHEVERLDE--SRKLELDGYLTKPTTRLARY 633

                          170       180
                   ....*....|....*....|....*...
gi 1039751490  338 QLLLKDFLRYSEKAGLECSDIEKAVELM 365
Cdd:COG5422    634 PLLLEEVLKFTDPDNPDTEDIPKVIDML 661

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 1039751490 356 SDIEKAVELMCLVPKRCNDM-------MNLGRLQ----GFEG-TLTAQGKLLQQDTFyvieldaGMQSRTKERRVFLFEQ 423
Cdd:cd13243     2 SVVEEALDTMTQVAWHINDMkrkhehaVRVQEIQslldGWEGpELTTYGDLVLEGTF-------RMAGAKNERLLFLFDK 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039751490 424 IVifseLLRKGSLTPGYMFKRSIKMNYLVLEDNVDGDPCKFALMNRETSE-RVILQAANSDIQQAWVQDINQVL 496
Cdd:cd13243    75 ML----LITKKREDGILQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNPKlQYTLQAKNQEQKRLWTQEIKRLI 144

PH domain; This entry contains a PH domain found in RhoGEF proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 385 EGTLTAQGKLLQQDTFYVIEL-DAGMQSRTKERRVFLFEQIVIFSELLRKGS-------LTPGYMFKRSI 446
Cdd:pfam19057   4 KLLSSGQRYLIRQDDVVETVYnERGEVLKSKERRLFLLNDLLVCVTVNSKSGsdfgslpGGEKYKLKWSV 73

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 411 SRTKERRVFLFE-QIVIFSELLRKGSLTPgymfKRSIKMN----YLVLEDNVDGDPCKFALM--NRETSERVILQAANSD 483
Cdd:pfam00169  16 KSWKKRYFVLFDgSLLYYKDDKSGKSKEP----KGSISLSgcevVEVVASDSPKRKFCFELRtgERTGKRTYLLQAESEE 91

                          90
                  ....*....|....
gi 1039751490 484 IQQAWVQDINQVLE 497
Cdd:pfam00169  92 ERKDWIKAIQSAIR 105

Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho family GEF, preferentially stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42 in vitro. It also possesses transforming activity. RhoGEF3/XPLN contains a tandem Dbl homology and PH domain, but lacks homology with other known functional domains or motifs. It is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. 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 1039751490 418 VFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYLVLEDNVDGDP-----CKFALMNRETSERVI--------------LQ 478
Cdd:cd10572    36 VFLFEEVLVLTRPVTRNEQLCYQVYRQPIPVADLVLEDLPDGEVrlggsFRGAFSNNERAKNFFrvsftdrslgqshtLQ 115

                          90
                  ....*....|....*..
gi 1039751490 479 AANSDIQQAWVQDINQV 495
Cdd:cd10572   116 ANDEFDKQQWLNCIRQA 132