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 521587499 304 VIPVHQGILERKKRFTKTYKESFYVLTPAGYLHEHGSSDQTKHPQPELSLFLPECTLGPPSTMASKSHKFHIEGRKVTGG 383
Cdd:cd13311    1 TKPLISGILERKSKFLKSYSKGYYVLTPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 521587499 384 QsaipqkgiaslgMGREHAYTFRARSHEEMMEWWNDIKQLSK 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 521587499 304 VIPVHQGILERKKRFTKTYKESFYVLTPAGYLHEHGSSDQTKHPQPELSLFLPECTLGPPSTMASKSHKFHIEGRKVTGG 383
Cdd:cd13311    1 TKPLISGILERKSKFLKSYSKGYYVLTPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 521587499 384 QsaipqkgiaslgMGREHAYTFRARSHEEMMEWWNDIKQLSK 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 521587499   306 PVHQGILERK-KRFTKTYKESFYVLTPaGYLHEHGSSDQTKHPQPELSLFLPECTLGPPSTMASKSHKFHIEgrkvtggq 384
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFN-STLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFE-------- 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 521587499   385 saipqkgiasLGMGREHAYTFRARSHEEMMEWWNDIKQLSK 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 521587499 304 VIPVHQGILERKKRFTKTYKESFYVLTPAGYLHEHGSSDQTKHPQPELSLFLPECTLGPPSTMASKSHKFHIEGRKVTGG 383
Cdd:cd13311    1 TKPLISGILERKSKFLKSYSKGYYVLTPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 521587499 384 QsaipqkgiaslgMGREHAYTFRARSHEEMMEWWNDIKQLSK 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 521587499   306 PVHQGILERK-KRFTKTYKESFYVLTPaGYLHEHGSSDQTKHPQPELSLFLPECTLGPPSTMASKSHKFHIEgrkvtggq 384
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFN-STLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFE-------- 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 521587499   385 saipqkgiasLGMGREHAYTFRARSHEEMMEWWNDIKQLSK 425
Cdd:smart00233  72 ----------IKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

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 521587499 306 PVHQGILERKKRFTKTYKESFYVLTpAGYLHEHGSSDQTKhpqPELSLFLPECTLGPPSTMASKSHKFHIEgrkvtggqs 385
Cdd:cd13263    3 PIKSGWLKKQGSIVKNWQQRWFVLR-GDQLYYYKDEDDTK---PQGTIPLPGNKVKEVPFNPEEPGKFLFE--------- 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 521587499 386 AIPQKGIASLGMGREhAYTFRARSHEEMMEWwndIKQLSKV 426
Cdd:cd13263   70 IIPGGGGDRMTSNHD-SYLLMANSQAEMEEW---VKVIRRV 106