Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281365757  508 PKTPTGLSNPpvTPVPPLSNNVVITGHNRHGI----PVTSGGVT-VTTSPSKVRPHSQGPSTLLNSSTVLMKYSTdALNQ 582
Cdd:pfam17823  66 APAPVTLTKG--TSAAHLNSTEVTAEHTPHGTdlsePATREGAAdGAASRALAAAASSSPSSAAQSLPAAIAALP-SEAF 142

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281365757  583 SVGSISIPQSAAVATlPSTQTQNAVSVHHASPALPQSASNGHAKSVMKLPVNGNSEVIVSGPTTnVAPRRSDNTSRT 659
Cdd:pfam17823 143 SAPRAAACRANASAA-PRAAIAAASAPHAASPAPRTAASSTTAASSTTAASSAPTTAASSAPAT-LTPARGISTAAT 217

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 281365757   873 PMIEGQLKEKKGKWRlfRRWRTRYFTLSGAHLSC-------KGSSGGESIDVNQIR-SVKVSRGARNIPKAFEIFTADQ- 943
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYykskkdkKSYKPKGSIDLSGCTvREAPDPDSSKKPHCFEIKTSDRk 78

                           90       100
                   ....*....|....*....|....
gi 281365757   944 TLILKPKDGKNAEEWVQCLSIVVA 967
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKAIA 102

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281365757  508 PKTPTGLSNPpvTPVPPLSNNVVITGHNRHGI----PVTSGGVT-VTTSPSKVRPHSQGPSTLLNSSTVLMKYSTdALNQ 582
Cdd:pfam17823  66 APAPVTLTKG--TSAAHLNSTEVTAEHTPHGTdlsePATREGAAdGAASRALAAAASSSPSSAAQSLPAAIAALP-SEAF 142

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281365757  583 SVGSISIPQSAAVATlPSTQTQNAVSVHHASPALPQSASNGHAKSVMKLPVNGNSEVIVSGPTTnVAPRRSDNTSRT 659
Cdd:pfam17823 143 SAPRAAACRANASAA-PRAAIAAASAPHAASPAPRTAASSTTAASSTTAASSAPTTAASSAPAT-LTPARGISTAAT 217

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 281365757 876 EGQLkEKKGKWrlFRRWRTRYFTLSGAHL-SCKGSSGG------ESIDVNQIRSVKVSRGARNIPKAFEIFTADQTLILK 948
Cdd:cd13276    2 AGWL-EKQGEF--IKTWRRRWFVLKQGKLfWFKEPDVTpyskprGVIDLSKCLTVKSAEDATNKENAFELSTPEETFYFI 78

                         90       100
                 ....*....|....*....|....*..
gi 281365757 949 PKDGKNAEEWVQCL--SIVVAHSQARD 973
Cdd:cd13276   79 ADNEKEKEEWIGAIgrAIVKHSRSVTD 105

Pleckstrin homology (PH) 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 281365757 875 IEGQLKEKKGKwrLFRRWRTRYFTLSGAHLSC------KGSSGGESIDVNQIRSVK-VSRGARniPKAFEIFTAD-QTLI 946
Cdd:cd00821    1 KEGYLLKRGGG--GLKSWKKRWFVLFEGVLLYykskkdSSYKPKGSIPLSGILEVEeVSPKER--PHCFELVTPDgRTYY 76

                         90
                 ....*....|....*.
gi 281365757 947 LKPKDGKNAEEWVQCL 962
Cdd:cd00821   77 LQADSEEERQEWLKAL 92

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 281365757 881 EKKGKWRlfRRWRTRYFTLSGAHLSCKGSSGG----ESIDVNQIRSVkVSRGARNIPKAFEIFTADQTLILKPKDGKNAE 956
Cdd:cd13255   13 EKKGERR--KTWKKRWFVLRPTKLAYYKNDKEyrllRLIDLTDIHTC-TEVQLKKHDNTFGIVTPARTFYVQADSKAEME 89

                 ....*.
gi 281365757 957 EWVQCL 962
Cdd:cd13255   90 SWISAI 95

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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 281365757 876 EGQL---KEKKGKWRLFRRWRTRYFTLSGAHLSCKGSSGGE---SIDVNQIRSV-KVSRGARNIPKAFEIFTADQTLILK 948
Cdd:cd01244    2 EGYLikrAQGRKKKFGRKNFKKRYFRLTNEALSYSKSKGKQplcSIPLEDILAVeRVEEESFKMKNMFQIVQPDRTLYLQ 81

                         90       100
                 ....*....|....*....|....
gi 281365757 949 PKDGKNAEEWVQCLSIVVAHSQAR 972
Cdd:cd01244   82 AKNVVELNEWLSALRKVCLCNPNR 105

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 281365757 885 KWRLF-RRWRTRYFTLSGAHLSCKGSSGGESIDVNQIRSVKVS--RGARNIPKAFEIFTADQTLILKPKDGKNAEEWVQC 961
Cdd:cd13294    7 KWVNYgKGWRSRWFVLQDGVLSYYKVHGPDKVKPSGEVHLKVSsiRESRSDDKKFYIFTGTKTLHLRAESREDRAAWLEA 86

                 .
gi 281365757 962 L 962
Cdd:cd13294   87 L 87

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 281365757 871 NQPMIEGQLkEKKGKWRlfRRWRTRYFTLSGAHLSC----KGSSGGESIDVNQIRSVKVSRGARNiPKAFEIFTADQTLI 946
Cdd:cd13298    4 DRVLKSGYL-LKRSRKT--KNWKKRWVVLRPCQLSYykdeKEYKLRRVINLSELLAVAPLKDKKR-KNVFGIYTPSKNLH 79

                         90
                 ....*....|....*.
gi 281365757 947 LKPKDGKNAEEWVQCL 962
Cdd:cd13298   80 FRATSEKDANEWVEAL 95