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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958750817  15 NSQEVFDLSDYEKCEELRKSKSR-SKKNHSKFTLARCRQPGTTAPNLIFLAVSPEEKESWINAL 77
Cdd:cd13317    39 KEEKVFDLEDYELCEYLRCSKSRaSKKNKSRFTLIRSKQPGNKAPDLKFQAVSPEEKESWINAL 102

Pleckstrin homology domain-containing family O Pleckstrin homology domain; The PLEKHO family members are PLEKHO1 (also called CKIP-1/Casein kinase 2-interacting protein 1/CK2-interacting protein 1) and PLEKHO2 (PLEKHQ1/PH domain-containing family Q member 1). They both contain a single PH domain. PLEKHO1 acts as a scaffold protein that functions in plasma membrane recruitment, transcriptional activity modulation, and posttranscriptional modification regulation. As an adaptor protein it is involved in signaling pathways, apoptosis, differentiation, cytoskeleton, and bone formation. Not much is know about PLEKHO2. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958750817  15 NSQEVFDLSDYEKCEELRKSKSR-SKKNHSKFTLARCRQPGTTAPNLIFLAVSPEEKESWINAL 77
Cdd:cd13317    39 KEEKVFDLEDYELCEYLRCSKSRaSKKNKSRFTLIRSKQPGNKAPDLKFQAVSPEEKESWINAL 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958750817    8 KRVKDEKNSQEVFDLSDYEkCEELRKSKSRSKKNHskFTLaRCRQPGTtapnLIFLAVSPEEKESWINALSSAI 81
Cdd:smart00233  36 KKDKKSYKPKGSIDLSGCT-VREAPDPDSSKKPHC--FEI-KTSDRKT----LLLQAESEEEREKWVEALRKAI 101

Pleckstrin homology domain-containing family O Pleckstrin homology domain; The PLEKHO family members are PLEKHO1 (also called CKIP-1/Casein kinase 2-interacting protein 1/CK2-interacting protein 1) and PLEKHO2 (PLEKHQ1/PH domain-containing family Q member 1). They both contain a single PH domain. PLEKHO1 acts as a scaffold protein that functions in plasma membrane recruitment, transcriptional activity modulation, and posttranscriptional modification regulation. As an adaptor protein it is involved in signaling pathways, apoptosis, differentiation, cytoskeleton, and bone formation. Not much is know about PLEKHO2. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958750817  15 NSQEVFDLSDYEKCEELRKSKSR-SKKNHSKFTLARCRQPGTTAPNLIFLAVSPEEKESWINAL 77
Cdd:cd13317    39 KEEKVFDLEDYELCEYLRCSKSRaSKKNKSRFTLIRSKQPGNKAPDLKFQAVSPEEKESWINAL 102

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750817  10 VKDEKNSQEVFDLSdyeKCEELRKSKSRSKKNHSkFTLArcrqpgTTAPNLIFLAVSPEEKESWINALSSAITRAKNRIL 89
Cdd:cd13276    35 VTPYSKPRGVIDLS---KCLTVKSAEDATNKENA-FELS------TPEETFYFIADNEKEKEEWIGAIGRAIVKHSRSVT 104

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gi 1958750817  90 D 90
Cdd:cd13276   105 D 105