Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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 672042546 716 QPLIEGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKddPDDSPIELSKVQSVKAVAKkrRDRSLPRAFEIFTDNK 795
Cdd:cd01264    1 QPVIEGQLKEKKGRWKFFKRWRTRYFTLSGAQLSYRGGKSK--PDAPPIELSKIRSVKVVRK--KDRSIPKAFEIFTDDK 76

                         90       100
                 ....*....|....*....|....*....
gi 672042546 796 TYVFKAKDEKNAEEWLQCINVALAQAKER 824
Cdd:cd01264   77 TYVLKAKDEKNAEEWLQCLSIAVAQAHAR 105

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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 672042546 716 QPLIEGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKddPDDSPIELSKVQSVKAVAKkrRDRSLPRAFEIFTDNK 795
Cdd:cd01264    1 QPVIEGQLKEKKGRWKFFKRWRTRYFTLSGAQLSYRGGKSK--PDAPPIELSKIRSVKVVRK--KDRSIPKAFEIFTDDK 76

                         90       100
                 ....*....|....*....|....*....
gi 672042546 796 TYVFKAKDEKNAEEWLQCINVALAQAKER 824
Cdd:cd01264   77 TYVLKAKDEKNAEEWLQCLSIAVAQAHAR 105

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672042546  717 PLIEGKLKeKQVRWKFiKRWKTRYFTLAGNQLLFQKgKSKDDPDDSP---IELSKVQSVKAVAKKRRDRslPRAFEIFTD 793
Cdd:pfam00169   1 VVKEGWLL-KKGGGKK-KSWKKRYFVLFDGSLLYYK-DDKSGKSKEPkgsISLSGCEVVEVVASDSPKR--KFCFELRTG 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 672042546  794 N----KTYVFKAKDEKNAEEWLQCINVALA 819
Cdd:pfam00169  76 ErtgkRTYLLQAESEEERKDWIKAIQSAIR 105

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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 672042546 716 QPLIEGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKddPDDSPIELSKVQSVKAVAKkrRDRSLPRAFEIFTDNK 795
Cdd:cd01264    1 QPVIEGQLKEKKGRWKFFKRWRTRYFTLSGAQLSYRGGKSK--PDAPPIELSKIRSVKVVRK--KDRSIPKAFEIFTDDK 76

                         90       100
                 ....*....|....*....|....*....
gi 672042546 796 TYVFKAKDEKNAEEWLQCINVALAQAKER 824
Cdd:cd01264   77 TYVLKAKDEKNAEEWLQCLSIAVAQAHAR 105

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 672042546 719 IEGKLKEKqvRWKFIKRWKTRYFTLAGNQLLFQKgkSKDDPDDSP---IELSKVQSVKAVAKKRRdrslPRAFEIFT-DN 794
Cdd:cd00821    1 KEGYLLKR--GGGGLKSWKKRWFVLFEGVLLYYK--SKKDSSYKPkgsIPLSGILEVEEVSPKER----PHCFELVTpDG 72

                         90       100
                 ....*....|....*....|
gi 672042546 795 KTYVFKAKDEKNAEEWLQCI 814
Cdd:cd00821   73 RTYYLQADSEEERQEWLKAL 92

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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 672042546 720 EGKLkEKQVRWkfIKRWKTRYFTLAGNQLLFQKGkSKDDPDDSP---IELSKVQSVKAVakkRRDRSLPRAFEIFTDNKT 796
Cdd:cd13276    2 AGWL-EKQGEF--IKTWRRRWFVLKQGKLFWFKE-PDVTPYSKPrgvIDLSKCLTVKSA---EDATNKENAFELSTPEET 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 672042546 797 YVFKAKDEKNAEEWLQCINVALAQAkereSREVT 830
Cdd:cd13276   75 FYFIADNEKEKEEWIGAIGRAIVKH----SRSVT 104

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. 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 672042546 734 KRWKTRYFTLAGNQLLFQKgKSKDDPDDSPIELSKVQSVKAVAKKRRDRslprAFEIFTDNKTYVFKAKDEKNAEEWLQC 813
Cdd:cd13255   20 KTWKKRWFVLRPTKLAYYK-NDKEYRLLRLIDLTDIHTCTEVQLKKHDN----TFGIVTPARTFYVQADSKAEMESWISA 94

                         90
                 ....*....|...
gi 672042546 814 INVALAQAKERES 826
Cdd:cd13255   95 INLARQALRATIT 107

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. 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 672042546 713 QDGQPLIEGKLKEKQ--VRwkfiKRWKTRYFTLAGNQLLFQKgkSKDDPDdsPIELSKVQSVKAVAKKRRDRSLPR--AF 788
Cdd:cd13271    3 RAGRNVIKSGYCVKQgaVR----KNWKRRFFILDDNTISYYK--SETDKE--PLRTIPLREVLKVHECLVKSLLMRdnLF 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 672042546 789 EIFTDNKTYVFKAKDEKNAEEWLQCINVALaQAKERESRE 828
Cdd:cd13271   75 EIITTSRTFYIQADSPEEMHSWIKAISGAI-VARRGPSRS 113

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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 672042546 708 ATVINQDGQPLIEGKLKekqVRWKFIKRWKTRYFTLAGNQLLFQkGKSKDD--PDDSpIELSKVQSVKAVAKKRrdrSLP 785
Cdd:cd13215   12 AYLPKRSGAVIKSGYLS---KRSKRTLRYTRYWFVLKGDTLSWY-NSSTDLyfPAGT-IDLRYATSIELSKSNG---EAT 83

                         90       100
                 ....*....|....*....|....*....
gi 672042546 786 RAFEIFTDNKTYVFKAKDEKNAEEWLQCI 814
Cdd:cd13215   84 TSFKIVTNSRTYKFKADSETSADEWVKAL 112

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. 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 672042546 730 WK---FIKRWKTRYFTLAGN--QLLFQKGKSkddpDDSP---IELSKVQSVK------AVAKKRRDRSLpraFEIFTDNK 795
Cdd:cd01235   10 YKrgaLLKGWKQRWFVLDSTkhQLRYYESRE----DTKCkgfIDLAEVESVTpatpiiGAPKRADEGAF---FDLKTNKR 82

                         90       100
                 ....*....|....*....|
gi 672042546 796 TYVFKAKDEKNAEEWLQCIN 815
Cdd:cd01235   83 VYNFCAFDAESAQQWIEKIQ 102

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 672042546 702 CNNPEKATVINQdgQPLIEGKLKEKQVR-WKFIKRWKTRYFTLAGNQLLFQKGKSKDDPDDsPI-----ELSKVQsvkav 775
Cdd:cd13258    3 FNEKELAALSSQ--PAEKEGKIAERQMGgPKKSEVFKERWFKLKGNLLFYFRTNEFGDCSE-PIgaivlENCRVQ----- 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 672042546 776 akKRRDRSLPRAFEI-FTDN--KTYVFKAKDEKNAEEWLQCI 814
Cdd:cd13258   75 --MEEITEKPFAFSIvFNDEpeKKYIFSCRSEEQCEQWIEAL 114

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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 672042546 720 EGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFqkgkSKDDPDDSPIELSKVQSVKAVAKKRRDRSLPRAFEIF---TDNKT 796
Cdd:cd13308   12 SGTLTKKGGSQKTLQNWQLRYVIIHQGCVYY----YKNDQSAKPKGVFSLNGYNRRAAEERTSKLKFVFKIIhlsPDHRT 87

                         90       100
                 ....*....|....*....|....*
gi 672042546 797 YVFKAKDEKNAEEWLQCINVALAQA 821
Cdd:cd13308   88 WYFAAKSEDEMSEWMEYIRREIDHY 112

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672042546  724 KEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKDDPDDSPIELSKVQSVK--------AVAKKRRDRSLPRA---FEIFT 792
Cdd:pfam15413   1 IEGYLKKKGPKTWKHRWFAVLRNGVLFYYKSEKMKVVKHVIVLSNYIVGKlgtdiisgALFKIDNIRSETSDdllLEIST 80

                          90       100
                  ....*....|....*....|....*
gi 672042546  793 DNKTYVFKAKDEKNAEEWLQCINVA 817
Cdd:pfam15413  81 ETKIFFLYGDNNEETYEWVEALQEA 105

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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 672042546 717 PLIEGKLKeKQVrwKFIKRWKTRYFTLAGNQLLFQKgkskdDPDDS------PIELSKVQSVKAVAKKrRDRSLpraFEI 790
Cdd:cd13263    3 PIKSGWLK-KQG--SIVKNWQQRWFVLRGDQLYYYK-----DEDDTkpqgtiPLPGNKVKEVPFNPEE-PGKFL---FEI 70

                         90       100       110
                 ....*....|....*....|....*....|...
gi 672042546 791 F-----TDNK----TYVFKAKDEKNAEEWLQCI 814
Cdd:cd13263   71 IpggggDRMTsnhdSYLLMANSQAEMEEWVKVI 103

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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 672042546 734 KRWKTRYFTLAGNQLLFQKGKSKDDPDDSpIELSKVQSVKAVAKKRrdrslpraFEIFTDNKTYVFKAKDEKNAEEWLQC 813
Cdd:cd13253   16 KGFQKRWVVFDGLSLRYFDSEKDAYSKRI-IPLSAISTVRAVGDNK--------FELVTTNRTFVFRAESDDERNLWCST 86

                 ....*..
gi 672042546 814 INVALAQ 820
Cdd:cd13253   87 LQAAISE 93

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) 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
                 ....*....|....*....|....*....|....*....|
gi 672042546 785 PRAFEIFTDNKTYVFKAKDEKNAEEWLQCINVALAQAKER 824
Cdd:cd13251   68 KKCFDLISHNRTYHFQAEDENDANAWMSVLKNSKEQALNK 107

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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 672042546 733 IKRWKTRYFTLAGNQLLFQKgkskdDPDDSP----IELSKVQsVKAVAKKRRdrslPRAFEIFTDNKTYVFKA----KDE 804
Cdd:cd01252   16 VKSWKRRWFILTDNCLYYFE-----YTTDKEprgiIPLENLS-VREVEDKKK----PFCFELYSPSNGQVIKAcktdSDG 85

                         90       100       110
                 ....*....|....*....|....*....|...
gi 672042546 805 KNAE-----------------EWLQCINVALAQ 820
Cdd:cd01252   86 KVVEgnhtvyrisaaseeerdEWIKSIKASISR 118