Slm1 Pleckstrin homology (PH) domain; Slm1 is a component of the target of rapamycin complex 2 (TORC2) signaling pathway. It plays a role in the regulation of actin organization and is a target of sphingolipid signaling during the heat shock response. Slm1 contains a single PH domain that binds PtdIns(4,5)P2, PtdIns(4)P, and dihydrosphingosine 1-phosphate (DHS-1P). Slm1 possesses two binding sites for anionic lipids. The non-canonical binding site of the PH domain of Slm1 is used for ligand binding, and it is proposed that beta-spectrin, Tiam1 and ArhGAP9 also have this type of phosphoinositide 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 1023183628 304 VIPVHQGILERKKRFTKTYKESFYVLTPAGYLHEHGSSDPTKHPQPELSLFLPECTLGPPSTMAAKSHKFHIEGRKVTGN 383
Cdd:cd13311     1 TKPLISGILERKSKFLKSYSKGYYVLTPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1023183628 384 QsavaskglaslgMGREHAYTFRARSHDEMMEWWNDIKQLSK 425
Cdd:cd13311    81 K------------FHRGHEWVFKAESHEEMMAWWEDIKELTK 110

Slm1 Pleckstrin homology (PH) domain; Slm1 is a component of the target of rapamycin complex 2 (TORC2) signaling pathway. It plays a role in the regulation of actin organization and is a target of sphingolipid signaling during the heat shock response. Slm1 contains a single PH domain that binds PtdIns(4,5)P2, PtdIns(4)P, and dihydrosphingosine 1-phosphate (DHS-1P). Slm1 possesses two binding sites for anionic lipids. The non-canonical binding site of the PH domain of Slm1 is used for ligand binding, and it is proposed that beta-spectrin, Tiam1 and ArhGAP9 also have this type of phosphoinositide 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 1023183628 304 VIPVHQGILERKKRFTKTYKESFYVLTPAGYLHEHGSSDPTKHPQPELSLFLPECTLGPPSTMAAKSHKFHIEGRKVTGN 383
Cdd:cd13311     1 TKPLISGILERKSKFLKSYSKGYYVLTPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1023183628 384 QsavaskglaslgMGREHAYTFRARSHDEMMEWWNDIKQLSK 425
Cdd:cd13311    81 K------------FHRGHEWVFKAESHEEMMAWWEDIKELTK 110

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 1023183628  306 PVHQGILERK-KRFTKTYKESFYVLTPaGYLHEHGSSDPTKHPQPELSLFLPECTLGPPSTMAAKSHKFHIEgrkvtgnq 384
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFN-STLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFE-------- 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1023183628  385 savaskglasLGMGREHAYTFRARSHDEMMEWWNDIKQLSK 425
Cdd:smart00233  72 ----------IKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

Slm1 Pleckstrin homology (PH) domain; Slm1 is a component of the target of rapamycin complex 2 (TORC2) signaling pathway. It plays a role in the regulation of actin organization and is a target of sphingolipid signaling during the heat shock response. Slm1 contains a single PH domain that binds PtdIns(4,5)P2, PtdIns(4)P, and dihydrosphingosine 1-phosphate (DHS-1P). Slm1 possesses two binding sites for anionic lipids. The non-canonical binding site of the PH domain of Slm1 is used for ligand binding, and it is proposed that beta-spectrin, Tiam1 and ArhGAP9 also have this type of phosphoinositide 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 1023183628 304 VIPVHQGILERKKRFTKTYKESFYVLTPAGYLHEHGSSDPTKHPQPELSLFLPECTLGPPSTMAAKSHKFHIEGRKVTGN 383
Cdd:cd13311     1 TKPLISGILERKSKFLKSYSKGYYVLTPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1023183628 384 QsavaskglaslgMGREHAYTFRARSHDEMMEWWNDIKQLSK 425
Cdd:cd13311    81 K------------FHRGHEWVFKAESHEEMMAWWEDIKELTK 110

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 1023183628  306 PVHQGILERK-KRFTKTYKESFYVLTPaGYLHEHGSSDPTKHPQPELSLFLPECTLGPPSTMAAKSHKFHIEgrkvtgnq 384
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFN-STLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFE-------- 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1023183628  385 savaskglasLGMGREHAYTFRARSHDEMMEWWNDIKQLSK 425
Cdd:smart00233  72 ----------IKTSDRKTLLLQAESEEEREKWVEALRKAIA 102