Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462490948   4 QTGLSNPFRGLMKLGTVERRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLLRCESVGPAHSDGRFELVFSGKKLA 83
Cdd:cd13321    28 QMGLSNPFRGLLKLGTLERRGAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLLRCESVGPAHSDGRFELVFPGKKLA 107

                          90       100
                  ....*....|....*....|....*
gi 2462490948  84 LRASSQDEAEDWLDRVREALQKVRP 108
Cdd:cd13321   108 LRAPSRDEAEDWLDRIREALQKVRP 132

Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; PLEKHM1 is thought to function in vesicular transport in osteoclasts. Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6. PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C-terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. 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 2462490948   4 QTGLSNPFRGLMKLGTVERRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLLRCESVGPAHSDGRFELVFSGKKLA 83
Cdd:cd13321    28 QMGLSNPFRGLLKLGTLERRGAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLLRCESVGPAHSDGRFELVFPGKKLA 107

                          90       100
                  ....*....|....*....|....*
gi 2462490948  84 LRASSQDEAEDWLDRVREALQKVRP 108
Cdd:cd13321   108 LRAPSRDEAEDWLDRIREALQKVRP 132

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 2462490948   14 LMKLGTVERRGAMGI--WKELFCELSPLEFRLYLSNEEHTC--------VENCSLLRCESVGPAHSDGRFELVFS-GKKL 82
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYKSKKDKKSykpkgsidLSGCTVREAPDPDSSKKPHCFEIKTSdRKTL 80

                           90       100
                   ....*....|....*....|..
gi 2462490948   83 ALRASSQDEAEDWLDRVREALQ 104
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102

Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; PLEKHM1 is thought to function in vesicular transport in osteoclasts. Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6. PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C-terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. 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 2462490948   4 QTGLSNPFRGLMKLGTVERRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLLRCESVGPAHSDGRFELVFSGKKLA 83
Cdd:cd13321    28 QMGLSNPFRGLLKLGTLERRGAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLLRCESVGPAHSDGRFELVFPGKKLA 107

                          90       100
                  ....*....|....*....|....*
gi 2462490948  84 LRASSQDEAEDWLDRVREALQKVRP 108
Cdd:cd13321   108 LRAPSRDEAEDWLDRIREALQKVRP 132

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 2462490948   14 LMKLGTVERRGAMGI--WKELFCELSPLEFRLYLSNEEHTC--------VENCSLLRCESVGPAHSDGRFELVFS-GKKL 82
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYKSKKDKKSykpkgsidLSGCTVREAPDPDSSKKPHCFEIKTSdRKTL 80

                           90       100
                   ....*....|....*....|..
gi 2462490948   83 ALRASSQDEAEDWLDRVREALQ 104
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102

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 2462490948  164 IKESLLYLYMD---RTWMPYIFSLSLEALKCFRIRNNEKMLSDSHGVE----TIRDILPDTSLGGPSFFKIITA-KAVLK 235
Cdd:smart00233   2 IKEGWLYKKSGggkKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDlsgcTVREAPDPDSSKKPHCFEIKTSdRKTLL 81

                           90       100
                   ....*....|....*....|.
gi 2462490948  236 LQAGNAEEAALWRDLVRKVLA 256
Cdd:smart00233  82 LQAESEEEREKWVEALRKAIA 102

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 2462490948  14 LMKLGtvERRGAmgiWKELFCELSPLEFRLYLSNEEHtcvencSLLR---------CESVGPAHSDGRFELVFSGKKLAL 84
Cdd:cd13255    12 LEKKG--ERRKT---WKKRWFVLRPTKLAYYKNDKEY------RLLRlidltdihtCTEVQLKKHDNTFGIVTPARTFYV 80

                          90       100
                  ....*....|....*....|....*....
gi 2462490948  85 RASSQDEAEDW---LDRVREALQKVRPQQ 110
Cdd:cd13255    81 QADSKAEMESWisaINLARQALRATITPN 109