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 19483852      7 VLKEGVLEKRSGGLLQLWKRKRCVLTERGLQLFEAK--GTGGRPKE---LSFARIKAVECVESTGRHIYFTLVTEGGGEI 81
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKkdKKSYKPKGsidLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL 80

                   ....*
gi 19483852     82 DFRCP 86
Cdd:smart00233  81 LLQAE 85

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 19483852      7 VLKEGVLEKRSGGLLQLWKRKRCVLTERGLQLFEAK--GTGGRPKE---LSFARIKAVECVESTGRHIYFTLVTEGGGEI 81
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKkdKKSYKPKGsidLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL 80

                   ....*
gi 19483852     82 DFRCP 86
Cdd:smart00233  81 LLQAE 85

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 19483852   9 KEGVLEKRSGGLLQLWKRKRCVLTERGLQLFEAKGTGGRP--KELSFARIKAVECVESTGRHIYFTLVTEGGGEIDFRCP 86
Cdd:cd00821   1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKpkGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQAD 80

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 19483852      7 VLKEGVLEKRSGGLLQLWKRKRCVLTERGLQLFEAK--GTGGRPKE---LSFARIKAVECVESTGRHIYFTLVTEGGGEI 81
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKkdKKSYKPKGsidLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL 80

                   ....*
gi 19483852     82 DFRCP 86
Cdd:smart00233  81 LLQAE 85

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 19483852   9 KEGVLEKRSGGLLQLWKRKRCVLTERGLQLFEAKGTGGRP--KELSFARIKAVECVESTGRHIYFTLVTEGGGEIDFRCP 86
Cdd:cd00821   1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKpkGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQAD 80