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 1063721946  28 VAGILYKWTNYGKGWRSRWFLLRDGILSYSKIRRPENVnllspsddlrligdistdrllrmkscsgrsrrkhhKNIGIVH 107
Cdd:cd13294     1 VAGILYKWVNYGKGWRSRWFVLQDGVLSYYKVHGPDKV-----------------------------------KPSGEVH 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063721946 108 LKVSSYRESKSDHRKFYIFTATKTLHLRTDSRSDRAAWLQALASTRGIVPLQSIN 162
Cdd:cd13294    46 LKVSSIRESRSDDKKFYIFTGTKTLHLRAESREDRAAWLEALQAAKDMFPRMSLN 100

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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 1063721946  28 VAGILYKWTNYGKGWRSRWFLLRDGILSYSKIRRPENVnllspsddlrligdistdrllrmkscsgrsrrkhhKNIGIVH 107
Cdd:cd13294     1 VAGILYKWVNYGKGWRSRWFVLQDGVLSYYKVHGPDKV-----------------------------------KPSGEVH 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063721946 108 LKVSSYRESKSDHRKFYIFTATKTLHLRTDSRSDRAAWLQALASTRGIVPLQSIN 162
Cdd:cd13294    46 LKVSSIRESRSDDKKFYIFTGTKTLHLRAESREDRAAWLEALQAAKDMFPRMSLN 100

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 1063721946   30 GILYKWT-NYGKGWRSRWFLLRDGILSYSKIRrpenvnllspsddlrligdistdrllrmkscSGRSRRKHHKNIGIVHL 108
Cdd:smart00233   5 GWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSK-------------------------------KDKKSYKPKGSIDLSGC 53

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1063721946  109 KVSSYRESKSDHRK--FYIFTAT-KTLHLRTDSRSDRAAWLQAL 149
Cdd:smart00233  54 TVREAPDPDSSKKPhcFEIKTSDrKTLLLQAESEEEREKWVEAL 97

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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 1063721946  28 VAGILYKWTNYGKGWRSRWFLLRDGILSYSKIRRPENVnllspsddlrligdistdrllrmkscsgrsrrkhhKNIGIVH 107
Cdd:cd13294     1 VAGILYKWVNYGKGWRSRWFVLQDGVLSYYKVHGPDKV-----------------------------------KPSGEVH 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063721946 108 LKVSSYRESKSDHRKFYIFTATKTLHLRTDSRSDRAAWLQALASTRGIVPLQSIN 162
Cdd:cd13294    46 LKVSSIRESRSDDKKFYIFTGTKTLHLRAESREDRAAWLEALQAAKDMFPRMSLN 100

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063721946  33 YKWTNYGKGWRSRWF-LLRDGILSY---SKIRRPENVNLLSPSDDLRLIGDISTDRLLrmkscsgrsrrkhhknigivhl 108
Cdd:pfam15413   4 YLKKKGPKTWKHRWFaVLRNGVLFYyksEKMKVVKHVIVLSNYIVGKLGTDIISGALF---------------------- 61

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063721946 109 KVSSYRESKSDHRKFYIFTATKTLHLRTDSRSDRAAWLQAL 149
Cdd:pfam15413  62 KIDNIRSETSDDLLLEISTETKIFFLYGDNNEETYEWVEAL 102

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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 1063721946  30 GILYKWTNYGKGWRSRWFLLRDGILSYSKIRRPENVnllspsddlrligdistdrllrmkscsgRSRrkhhkniGIVHLK 109
Cdd:cd13292     6 GYLKKWTNYAKGYKTRWFVLEDGVLSYYRHQDDEGS----------------------------ACR-------GSINMK 50

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1063721946 110 VSSYRESKSDHRKFYIFTATKT---LHLRTDSRSDRAAWLQALAST 152
Cdd:cd13292    51 NARLVSDPSEKLRFEVSSKTSGspkWYLKANHPVEAARWIQALQKA 96

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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 1063721946  30 GILYKWTNYGKGWRSRWFLLRDGILSYskIRRPENVNllspsddlrligdistdrllrmKSCSGRsrrkhhknigivhLK 109
Cdd:cd13284     3 GWLLKWTNYIKGYQRRWFVLSNGLLSY--YRNQAEMA----------------------HTCRGT-------------IN 45

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1063721946 110 VSSYRESKSDHRKFYIFTATK-TLHLRTDSRSDRAAWLQAL--ASTRGIVPLQS 160
Cdd:cd13284    46 LAGAEIHTEDSCNFVISNGGTqTFHLKASSEVERQRWVTALelAKAKAIRLLES 99

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 1063721946   30 GILYKWT-NYGKGWRSRWFLLRDGILSYSKIRrpenvnllspsddlrligdistdrllrmkscSGRSRRKHHKNIGIVHL 108
Cdd:smart00233   5 GWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSK-------------------------------KDKKSYKPKGSIDLSGC 53

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1063721946  109 KVSSYRESKSDHRK--FYIFTAT-KTLHLRTDSRSDRAAWLQAL 149
Cdd:smart00233  54 TVREAPDPDSSKKPhcFEIKTSDrKTLLLQAESEEEREKWVEAL 97

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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 1063721946  30 GILYKWTNYG-KGWRSRWFLLRDGILSYSKirRPENVNLLSPSDDLRLigdistdrllrmkscsgrsrrkhhknigivhl 108
Cdd:cd13250     3 GYLFKRSSNAfKTWKRRWFSLQNGQLYYQK--RDKKDEPTVMVEDLRL-------------------------------- 48

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1063721946 109 kvSSYRESKSDHRK--FYIFTATKTLHLRTDSRSDRAAWLQALAST 152
Cdd:cd13250    49 --CTVKPTEDSDRRfcFEVISPTKSYMLQAESEEDRQAWIQAIQSA 92

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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 1063721946  28 VAGILYKWTNYGKGWRSRWFLLRD--GILSYSKirrpenvnllspsddlrligdiSTDRLLRmkscsgRSRRkhhkniGI 105
Cdd:cd13290     1 MEGPLSKWTNVMKGWQYRWFVLDDnaGLLSYYT----------------------SKEKMMR------GSRR------GC 46

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1063721946 106 VHLKVSSYRESKSDHRKFYIFTATKTLHLRTDSRSDRAAWLQALASTR 153
Cdd:cd13290    47 VRLKGAVVGIDDEDDSTFTITVDQKTFHFQARDAEERERWIRALEDTI 94

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063721946  30 GILYKWTNY-GKGWRSRWFLLRDGILSYSKIRRPENVNLLSPSDDLRLIGDISTDRLLRMKscsgrsrRKHHKNIgivhl 108
Cdd:pfam00169   5 GWLLKKGGGkKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVVASDSPK-------RKFCFEL----- 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063721946 109 kvssyresksdhrKFYIFTATKTLHLRTDSRSDRAAWLQAL 149
Cdd:pfam00169  73 -------------RTGERTGKRTYLLQAESEEERKDWIKAI 100

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. 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 1063721946  29 AGILYKWTNYGKGWRSRWFLLRDGILSYSKirrpenvnllSPSDDLRligdistdrllrmkscsgrsrrkhhKNIGIVHL 108
Cdd:cd13282     2 AGYLTKLGGKVKTWKRRWFVLKNGELFYYK----------SPNDVIR-------------------------KPQGQIAL 46

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063721946 109 KVSSYRESKSDHRKFYIFTATKTLHLRTDSRSDRAAWLQAL 149
Cdd:cd13282    47 DGSCEIARAEGAQTFEIVTEKRTYYLTADSENDLDEWIRVI 87