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 1196925420 1332 FQLRHGNDLLAMDAIRGCDVNLKEQGQLRCRDEFIVCCGRKKYLRHVFLFEDLILFSKTQKVEGSHDVYLYKQSFKTAEI 1411
Cdd:cd13242      2 FQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSDI 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1196925420 1412 GMTENVGDSGLRFEIWFrRRRKSQDTYILQASSAEVKSAWTDVIGRILWRQALKSR 1467
Cdd:cd13242     82 GLTENVGDSGLKFEIWF-RRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420  186 AVHRAPWSDVTDPVFVPSPGAILQSYSSCTGPERLPSSPSEAPVPTQATAGPHFQGSAScpdtltspcRRGHTGSDQLRH 265
Cdd:PHA03307   140 PVGSPGPPPAASPPAAGASPAAVASDAASSRQAALPLSSPEETARAPSSPPAEPPPSTP---------PAAASPRPPRRS 210

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420  266 LPypERAELGSPRTLSGSSDRDFEKVSPSEQGPRMPPE-NCGGSGERPDPMDQedrPKALTFHTDLGIPSSRRRPpgDPT 344
Cdd:PHA03307   211 SP--ISASASSPAPAPGRSAADDAGASSSDSSSSESSGcGWGPENECPLPRPA---PITLPTRIWEASGWNGPSS--RPG 283

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420  345 CVQPRRWFRESYMEAlrnpmplGSSEEALGDLACSSLTGASRDLGTGAVASGTQEETSGPRGDPQQTPSLEKERHTPSRT 424
Cdd:PHA03307   284 PASSSSSPRERSPSP-------SPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSPGPSPSRSPSPSRP 356

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1196925420  425 GPGAAGRTLPRRSRSWERAP----------RSSRGAQAAACHTSHHSAGSRPGG 468
Cdd:PHA03307   357 PPPADPSSPRKRPRPSRAPSspaasagrptRRRARAAVAGRARRRDATGRFPAG 410

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 1196925420 1332 FQLRHGNDLLAMDAIRGCDVNLKEQGQLRCRDEFIVCCGRKKYLRHVFLFEDLILFSKTQKVEGSHDVYLYKQSFKTAEI 1411
Cdd:cd13242      2 FQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSDI 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1196925420 1412 GMTENVGDSGLRFEIWFrRRRKSQDTYILQASSAEVKSAWTDVIGRILWRQALKSR 1467
Cdd:cd13242     82 GLTENVGDSGLKFEIWF-RRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

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 1196925420 1162 LRHIMAEMIATEREYIRCLGYVIDNYFPEMERMDLPqGLRGKHHVIFGNLEKLHDFHQQHFLRELERCQ---HCPLAVGR 1238
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEewdKSGPRIGD 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1196925420 1239 SFLRHEEQFGMYVIYSKNKPQSDALLSSH--GNAFFKD---KQRELGDKMDLASYLLRPVQRVAKYALLLQDLLK 1308
Cdd:cd00160     80 VFLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEfleKAESECGRLKLESLLLKPVQRLTKYPLLLKELLK 154

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 1196925420  1356 QGQLRCRDEFIvccGRKKYLRHVFLFEDLILFSKTQKVEGSHDvylYKQSFKTAEIGMTENVGDSGLR----FEIWFRRR 1431
Cdd:smart00233    4 EGWLYKKSGGG---KKSWKKRYFVLFNSTLLYYKSKKDKKSYK---PKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*...
gi 1196925420  1432 RksqdTYILQASSAEVKSAWTDVIGRIL 1459
Cdd:smart00233   78 K----TLLLQAESEEEREKWVEALRKAI 101

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420 1376 RHVFLFEDLILFSKTQKVEGSHDvYLYKQSFKTAEIGMTENVGDSGLR--FEIWFRRRRKSQdTYILQASSAEVKSAWTD 1453
Cdd:pfam00169   21 RYFVLFDGSLLYYKDDKSGKSKE-PKGSISLSGCEVVEVVASDSPKRKfcFELRTGERTGKR-TYLLQAESEEERKDWIK 98

                   ....*.
gi 1196925420 1454 VIGRIL 1459
Cdd:pfam00169   99 AIQSAI 104

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 1196925420 1332 FQLRHGNDLLAMDAIRGCDVNLKEQGQLRCRDEFIVCCGRKKYLRHVFLFEDLILFSKTQKVEGSHDVYLYKQSFKTAEI 1411
Cdd:cd13242      2 FQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSDI 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1196925420 1412 GMTENVGDSGLRFEIWFrRRRKSQDTYILQASSAEVKSAWTDVIGRILWRQALKSR 1467
Cdd:cd13242     82 GLTENVGDSGLKFEIWF-RRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

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 1196925420 1162 LRHIMAEMIATEREYIRCLGYVIDNYFPEMERMDLPqGLRGKHHVIFGNLEKLHDFHQQHFLRELERCQ---HCPLAVGR 1238
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEewdKSGPRIGD 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1196925420 1239 SFLRHEEQFGMYVIYSKNKPQSDALLSSH--GNAFFKD---KQRELGDKMDLASYLLRPVQRVAKYALLLQDLLK 1308
Cdd:cd00160     80 VFLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEfleKAESECGRLKLESLLLKPVQRLTKYPLLLKELLK 154

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) 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. 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 1196925420 1345 AIRGCDVNLKEQGQLRCRDEFIVCCGRKK-----------YLRHVFLFEDLILFSKTQKVEGSHDVYLYKQSFKTAEIGM 1413
Cdd:cd01227      1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKghtkklarfkpMQRHIFLYEKAVLFCKKRGENGEAPSYSYKNSLNTTAVGL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1196925420 1414 TENVGDSGLRFEIWFRRRrksQDTYILQASSAEVKSAWTDVIGRILWRQ 1462
Cdd:cd01227     81 TENVKGDTKKFEIWLNGR---EEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

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 1196925420 1348 GCDVNLKEQGQLRCRDEFIV----CCGRKKYLRHVFLFEDLILFSKTQKVEGSHDVYLYKQSFKTAEIGMTENVGDSGLR 1423
Cdd:cd13240      4 GCDEDLDSLGEVILQDSFQVwdpkQLIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGDPCK 83

                           90       100
                   ....*....|....*....|....*...
gi 1196925420 1424 FEIWFRRRRKSQDTYILQASSAEVKSAW 1451
Cdd:cd13240     84 FALWTGRVPTSDNKIVLKASSLEVKQTW 111

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 1196925420 1371 RKKYLRHVFLFEDLILFSKTQKVEGshdvYLYKQSFKTAEIGMTENVGDSGLRFEIWFRRRRKSQdtYILQASSAEVKSA 1450
Cdd:cd13243     62 GAKNERLLFLFDKMLLITKKREDGI----LQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNPKLQ--YTLQAKNQEQKRL 135

                   ....*....
gi 1196925420 1451 WTDVIGRIL 1459
Cdd:cd13243    136 WTQEIKRLI 144

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420  186 AVHRAPWSDVTDPVFVPSPGAILQSYSSCTGPERLPSSPSEAPVPTQATAGPHFQGSAScpdtltspcRRGHTGSDQLRH 265
Cdd:PHA03307   140 PVGSPGPPPAASPPAAGASPAAVASDAASSRQAALPLSSPEETARAPSSPPAEPPPSTP---------PAAASPRPPRRS 210

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420  266 LPypERAELGSPRTLSGSSDRDFEKVSPSEQGPRMPPE-NCGGSGERPDPMDQedrPKALTFHTDLGIPSSRRRPpgDPT 344
Cdd:PHA03307   211 SP--ISASASSPAPAPGRSAADDAGASSSDSSSSESSGcGWGPENECPLPRPA---PITLPTRIWEASGWNGPSS--RPG 283

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196925420  345 CVQPRRWFRESYMEAlrnpmplGSSEEALGDLACSSLTGASRDLGTGAVASGTQEETSGPRGDPQQTPSLEKERHTPSRT 424
Cdd:PHA03307   284 PASSSSSPRERSPSP-------SPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSPGPSPSRSPSPSRP 356

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1196925420  425 GPGAAGRTLPRRSRSWERAP----------RSSRGAQAAACHTSHHSAGSRPGG 468
Cdd:PHA03307   357 PPPADPSSPRKRPRPSRAPSspaasagrptRRRARAAVAGRARRRDATGRFPAG 410

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 1196925420 1356 QGQLRCRDEFiVCCGRKKylRHVFLFEDLILFSKTQKVegshDVYLYKQSFKTAEIGMTENVGDSGLR--FEIWFRRRRk 1433
Cdd:cd00821      2 EGYLLKRGGG-GLKSWKK--RWFVLFEGVLLYYKSKKD----SSYKPKGSIPLSGILEVEEVSPKERPhcFELVTPDGR- 73

                           90       100
                   ....*....|....*....|..
gi 1196925420 1434 sqdTYILQASSAEVKSAWTDVI 1455
Cdd:cd00821     74 ---TYYLQADSEEERQEWLKAL 92

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. 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 1196925420 1361 CRDEFI-------VCCGRKKYLRHVFLFEDLILFSKTQKVEGSHDV----YLYKQSF--KTAEIGMTENVGDSGLRFEIw 1427
Cdd:cd01261      2 CCNEFImegtlgkVGSGKRKTERHAFLFDGLLLLCKSNRRRTSTGGpkpeYRLKEKFfiRKVEINDLEDTEELKNAFEI- 80

                           90       100
                   ....*....|....*....|....
gi 1196925420 1428 frrRRKSQDTYILQASSAEVKSAW 1451
Cdd:cd01261     81 ---VPRDQPSVILFAKSAEEKNNW 101