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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024347682  15 PAPSAEKFGWIKKSSGGLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQELRALLKKKNRFILIRS--PGK 92
Cdd:cd13317     1 GAPQPEKAGWIKKSSGGLLGIWKDRYVVLKGTQLLVYEKEEKVFDLEDYELCEYLRCSKSRASKKNKSRFTLIRSkqPGN 80

                          90       100
                  ....*....|....*....|..
gi 2024347682  93 KVHDIKFQAPTSEEKESWIKAL 114
Cdd:cd13317    81 KAPDLKFQAVSPEEKESWINAL 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024347682  15 PAPSAEKFGWIKKSSGGLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQELRALLKKKNRFILIRS--PGK 92
Cdd:cd13317     1 GAPQPEKAGWIKKSSGGLLGIWKDRYVVLKGTQLLVYEKEEKVFDLEDYELCEYLRCSKSRASKKNKSRFTLIRSkqPGN 80

                          90       100
                  ....*....|....*....|..
gi 2024347682  93 KVHDIKFQAPTSEEKESWIKAL 114
Cdd:cd13317    81 KAPDLKFQAVSPEEKESWINAL 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024347682   21 KFGWIKKSSGGLLGLWKDRYVQLRKTQLVVYEDEDEQ---KCIETVELESYDKCQELRALLKKKNRFILIRSPGKKVHdi 97
Cdd:smart00233   3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL-- 80

                           90       100
                   ....*....|....*....|..
gi 2024347682   98 KFQAPTSEEKESWIKALNEGIN 119
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024347682  15 PAPSAEKFGWIKKSSGGLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQELRALLKKKNRFILIRS--PGK 92
Cdd:cd13317     1 GAPQPEKAGWIKKSSGGLLGIWKDRYVVLKGTQLLVYEKEEKVFDLEDYELCEYLRCSKSRASKKNKSRFTLIRSkqPGN 80

                          90       100
                  ....*....|....*....|..
gi 2024347682  93 KVHDIKFQAPTSEEKESWIKAL 114
Cdd:cd13317    81 KAPDLKFQAVSPEEKESWINAL 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024347682   21 KFGWIKKSSGGLLGLWKDRYVQLRKTQLVVYEDEDEQ---KCIETVELESYDKCQELRALLKKKNRFILIRSPGKKVHdi 97
Cdd:smart00233   3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL-- 80

                           90       100
                   ....*....|....*....|..
gi 2024347682   98 KFQAPTSEEKESWIKALNEGIN 119
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. 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 2024347682  36 WKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQELRAlLKKKNRFIlIRSPGKKVHdikFQAPTSEEKESWIKALN 115
Cdd:cd13298    22 WKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVAPLKD-KKRKNVFG-IYTPSKNLH---FRATSEKDANEWVEALR 96

                  .
gi 2024347682 116 E 116
Cdd:cd13298    97 E 97

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 2024347682  21 KFGWIKKSsGGLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELESyDKCQELRALLKKKNRFILIRSPGKKVHDIK-- 98
Cdd:cd13263     5 KSGWLKKQ-GSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPG-NKVKEVPFNPEEPGKFLFEIIPGGGGDRMTsn 82

                          90       100
                  ....*....|....*....|.
gi 2024347682  99 -----FQAPTSEEKESWIKAL 114
Cdd:cd13263    83 hdsylLMANSQAEMEEWVKVI 103

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 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 2024347682  36 WKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQELRalLKKKNRFILIRSPGKKVHdikFQAPTSEEKESWIKALN 115
Cdd:cd13255    22 WKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTDIHTCTEVQ--LKKHDNTFGIVTPARTFY---VQADSKAEMESWISAIN 96

                  .
gi 2024347682 116 E 116
Cdd:cd13255    97 L 97

Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; PLEKHM1 is thought to function in vesicular transport in osteoclasts. Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6. PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C-terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-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 2024347682  31 GLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELEsydKCQELrALLKKKNRFILIrSPGKKVHdikFQAPTSEEKESW 110
Cdd:cd13321    48 GAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLL---RCESV-GPAHSDGRFELV-FPGKKLA---LRAPSRDEAEDW 119

                          90
                  ....*....|
gi 2024347682 111 IKALNEGINR 120
Cdd:cd13321   120 LDRIREALQK 129

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second PH repeat. 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 2024347682  23 GWIKKSSGGLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQELRALLKKKNRFILIRSPGKKvhdIKFQAP 102
Cdd:cd13299    10 GYLQVLKKKGVNQWKKYWLVLRNRSLSFYKDQSEYSPVKIIPIDDIIDVVELDPLSKSKKWCLQIITPEKR---IRFCAD 86

                          90
                  ....*....|..
gi 2024347682 103 TSEEKESWIKAL 114
Cdd:cd13299    87 DEESLIKWLGAL 98

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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 2024347682  20 EKFGWIKKSSGGLLGlWKDRYVQLRKTQLVVYEDEDEQKCIETVELE--SYDKCQELrallKKKNRFILIRSPGKKV--- 94
Cdd:cd01252     4 DREGWLLKLGGRVKS-WKRRWFILTDNCLYYFEYTTDKEPRGIIPLEnlSVREVEDK----KKPFCFELYSPSNGQVika 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2024347682  95 -------------HDIKF-QAPTSEEKESWIKALNEGINR 120
Cdd:cd01252    79 cktdsdgkvvegnHTVYRiSAASEEERDEWIKSIKASISR 118

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. 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 2024347682  12 KPKPAPSAEKFGWIKKSsGGLLGLWKDRYVQLRKTQLVVYEDEDEQKCIETVELESYDKCQE--LRALLKKKNRFILIRS 89
Cdd:cd13271     1 RQRAGRNVIKSGYCVKQ-GAVRKNWKRRFFILDDNTISYYKSETDKEPLRTIPLREVLKVHEclVKSLLMRDNLFEIITT 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2024347682  90 PgkkvHDIKFQAPTSEEKESWIKALNEGINR 120
Cdd:cd13271    80 S----RTFYIQADSPEEMHSWIKAISGAIVA 106

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) domain; There are 2 types of ORPs found in Cryptosporidium: CpORP1 and CpORP2. Cryptosporium differs from other apicomplexans like Plasmodium, Toxoplasma, and Eimeria which possess only a single long-type ORP consisting of an N-terminal PH domain followed by a C-terminal ligand binding (LB) domain. CpORP2 is like this, but CpORP1 differs and has a truncated N-terminus resulting in only having a LB domain present. The exact functions of these proteins are largely unknown though CpORP1 is thought to be involved in lipid transport across the parasitophorous vacuole membrane. 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 2024347682  23 GWIKKSSGgLLGLWKDRYVQLRKtQLVVYEDEDEQKCIETVELESYDkcqeLRALLKKKNRFIlIRSPGKkvhDIKFQAP 102
Cdd:cd13293     3 GYLKKWTN-IFNSWKPRYFILYP-GILCYSKQKGGPKKGTIHLKICD----IRLVPDDPLRII-INTGTN---QLHLRAS 72

                          90
                  ....*....|..
gi 2024347682 103 TSEEKESWIKAL 114
Cdd:cd13293    73 SVEEKLKWYNAL 84

Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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 2024347682  26 KKSSGGLLGlWKDRYVQLRKtqLVVYEDEDEQKCIETVELESYDKCQELRALL--------KKKNRFILIRSPGKkvhDI 97
Cdd:cd13295    23 KKTPFGKRG-WKMFYATLKG--LVLYLHKDEYGCKKALRYESLRNAISVHHSLatkatdytKKPHVFRLRTADWR---EY 96

                          90
                  ....*....|....*...
gi 2024347682  98 KFQAPTSEEKESWIKALN 115
Cdd:cd13295    97 LFQASDTKEMQSWIEAIN 114