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 68341979  21 PEKVGWVRKFcgKGIFREIWKNRYVVLKGDQLYVSEKEVKdeknsqeVFDLSDYEKCEELRKSKSR-SKKNHSKFTLARC 99
Cdd:cd13317   5 PEKAGWIKKS--SGGLLGIWKDRYVVLKGTQLLVYEKEEK-------VFDLEDYELCEYLRCSKSRaSKKNKSRFTLIRS 75

                        90       100
                ....*....|....*....|....*..
gi 68341979 100 RQPGTTAPNLIFLAVSPEEKESWINAL 126
Cdd:cd13317  76 KQPGNKAPDLKFQAVSPEEKESWINAL 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 68341979  21 PEKVGWVRKFcgKGIFREIWKNRYVVLKGDQLYVSEKEVKdeknsqeVFDLSDYEKCEELRKSKSR-SKKNHSKFTLARC 99
Cdd:cd13317   5 PEKAGWIKKS--SGGLLGIWKDRYVVLKGTQLLVYEKEEK-------VFDLEDYELCEYLRCSKSRaSKKNKSRFTLIRS 75

                        90       100
                ....*....|....*....|....*..
gi 68341979 100 RQPGTTAPNLIFLAVSPEEKESWINAL 126
Cdd:cd13317  76 KQPGNKAPDLKFQAVSPEEKESWINAL 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 68341979     21 PEKVGWVRKFcgKGIFREIWKNRYVVLKGDQLYVSEKEVKDEKNS-QEVFDLSDYEkCEELRKSKSRSKKNHskFTLaRC 99
Cdd:smart00233   1 VIKEGWLYKK--SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKpKGSIDLSGCT-VREAPDPDSSKKPHC--FEI-KT 74

                           90       100       110
                   ....*....|....*....|....*....|.
gi 68341979    100 RQPGTtapnLIFLAVSPEEKESWINALSSAI 130
Cdd:smart00233  75 SDRKT----LLLQAESEEEREKWVEALRKAI 101

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 68341979  21 PEKVGWVRKFcgKGIFREIWKNRYVVLKGDQLYVSEKEVKdeknsqeVFDLSDYEKCEELRKSKSR-SKKNHSKFTLARC 99
Cdd:cd13317   5 PEKAGWIKKS--SGGLLGIWKDRYVVLKGTQLLVYEKEEK-------VFDLEDYELCEYLRCSKSRaSKKNKSRFTLIRS 75

                        90       100
                ....*....|....*....|....*..
gi 68341979 100 RQPGTTAPNLIFLAVSPEEKESWINAL 126
Cdd:cd13317  76 KQPGNKAPDLKFQAVSPEEKESWINAL 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 68341979     21 PEKVGWVRKFcgKGIFREIWKNRYVVLKGDQLYVSEKEVKDEKNS-QEVFDLSDYEkCEELRKSKSRSKKNHskFTLaRC 99
Cdd:smart00233   1 VIKEGWLYKK--SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKpKGSIDLSGCT-VREAPDPDSSKKPHC--FEI-KT 74

                           90       100       110
                   ....*....|....*....|....*....|.
gi 68341979    100 RQPGTtapnLIFLAVSPEEKESWINALSSAI 130
Cdd:smart00233  75 SDRKT----LLLQAESEEEREKWVEALRKAI 101

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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 68341979  23 KVGWVRKfcgKGIFREIWKNRYVVLKGDQLY-VSEKEVKDEKNSQEVFDLSdyeKCEELRKSKSRSKKNHSkFTLArcrq 101
Cdd:cd13276   1 KAGWLEK---QGEFIKTWRRRWFVLKQGKLFwFKEPDVTPYSKPRGVIDLS---KCLTVKSAEDATNKENA-FELS---- 69

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 68341979 102 pgTTAPNLIFLAVSPEEKESWINALSSAITRAKNRILD 139
Cdd:cd13276  70 --TPEETFYFIADNEKEKEEWIGAIGRAIVKHSRSVTD 105

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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 68341979  21 PEKVGWVRKFCGKGIfrEIWKNRYVVLKGDQLYVSeKEVKDEKnSQEVFDLSDYeKCEELRKSKSRSKKNhsKFTLARCr 100
Cdd:cd13248   7 VVMSGWLHKQGGSGL--KNWRKRWFVLKDNCLYYY-KDPEEEK-ALGSILLPSY-TISPAPPSDEISRKF--AFKAEHA- 78

                        90       100
                ....*....|....*....|....*....
gi 68341979 101 qpgtTAPNLIFLAVSPEEKESWINALSSA 129
Cdd:cd13248  79 ----NMRTYYFAADTAEEMEQWMNAMSLA 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 68341979  23 KVGWVRKfcgKGIFREIWKNRYVVLKGDQL--YVSEKEVKDEKnsqeVFDLSDYEKCEELrksksRSKKNHSKFtlarcr 100
Cdd:cd13255   8 KAGYLEK---KGERRKTWKKRWFVLRPTKLayYKNDKEYRLLR----LIDLTDIHTCTEV-----QLKKHDNTF------ 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 68341979 101 qpGTTAPNLIFL--AVSPEEKESWInalsSAITRAKNRILDEVTV 143
Cdd:cd13255  70 --GIVTPARTFYvqADSKAEMESWI----SAINLARQALRATITP 108

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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 68341979  22 EKVGWVRKFCGKGIFReIWKNRYVVLKGDQL--YVSEKEvKDEKNSQEVFDLSDYekceelrksksRSKKNhSKFTLArc 99
Cdd:cd13253   1 IKSGYLDKQGGQGNNK-GFQKRWVVFDGLSLryFDSEKD-AYSKRIIPLSAISTV-----------RAVGD-NKFELV-- 64

                        90       100       110
                ....*....|....*....|....*....|.
gi 68341979 100 rqpgTTAPNLIFLAVSPEEKESWINALSSAI 130
Cdd:cd13253  65 ----TTNRTFVFRAESDDERNLWCSTLQAAI 91

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain 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 68341979  33 KGIFREIWKNRYVVLKGDQL-YVSEKEVKDEK------NSQEVFDLSDYEKCEELRKSKSRSKKNHskftlarcrqpgtt 105
Cdd:cd13301  12 KGHVVNNWKARWFVLKEDGLeYYKKKTDSSPKgmiplkGCTITSPCLEYGKRPLVFKLTTAKGQEH-------------- 77

                        90       100
                ....*....|....*....|....*.
gi 68341979 106 apnlIFLAVSPEEKESWINALSSAIT 131
Cdd:cd13301  78 ----FFQACSREERDAWAKDITKAIT 99

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. 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 68341979  25 GWV-RKFCGKGIFREIWKNRYVVLKGDQLYVSEKEvKDEKnSQEVFDLSDY--EKCEELRKsKSRSKKNHSKFTlarcrq 101
Cdd:cd01260  17 GWLwKKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQ-QDEK-AEGFINLPDFkiERASECKK-KYAFKACHPKIK------ 87

                        90       100
                ....*....|....*....|....*....
gi 68341979 102 pgttapNLIFLAVSPEEKESWINALSSAI 130
Cdd:cd01260  88 ------TFYFAAENLDDMNKWLSKLNMAI 110