Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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 767927532 671 QPLIEGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKddPDDCPIELSKVQSVKAVAKkrRDRSLPRAFEIFTDNK 750
Cdd:cd01264    1 QPVIEGQLKEKKGRWKFFKRWRTRYFTLSGAQLSYRGGKSK--PDAPPIELSKIRSVKVVRK--KDRSIPKAFEIFTDDK 76

                         90       100
                 ....*....|....*....|....*....
gi 767927532 751 TYVFKAKDEKNAEEWLQCINVAVAQAKER 779
Cdd:cd01264   77 TYVLKAKDEKNAEEWLQCLSIAVAQAHAR 105

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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 767927532 671 QPLIEGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKddPDDCPIELSKVQSVKAVAKkrRDRSLPRAFEIFTDNK 750
Cdd:cd01264    1 QPVIEGQLKEKKGRWKFFKRWRTRYFTLSGAQLSYRGGKSK--PDAPPIELSKIRSVKVVRK--KDRSIPKAFEIFTDDK 76

                         90       100
                 ....*....|....*....|....*....
gi 767927532 751 TYVFKAKDEKNAEEWLQCINVAVAQAKER 779
Cdd:cd01264   77 TYVLKAKDEKNAEEWLQCLSIAVAQAHAR 105

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767927532  672 PLIEGKLKeKQVRWKFiKRWKTRYFTLAGNQLLFQKGKS--KDDPDDCPIELSKVQSVKAVAKKRRDRslPRAFEIFTDN 749
Cdd:pfam00169   1 VVKEGWLL-KKGGGKK-KSWKKRYFVLFDGSLLYYKDDKsgKSKEPKGSISLSGCEVVEVVASDSPKR--KFCFELRTGE 76

                          90       100
                  ....*....|....*....|....*....
gi 767927532  750 ----KTYVFKAKDEKNAEEWLQCINVAVA 774
Cdd:pfam00169  77 rtgkRTYLLQAESEEERKDWIKAIQSAIR 105

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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 767927532 671 QPLIEGKLKEKQVRWKFIKRWKTRYFTLAGNQLLFQKGKSKddPDDCPIELSKVQSVKAVAKkrRDRSLPRAFEIFTDNK 750
Cdd:cd01264    1 QPVIEGQLKEKKGRWKFFKRWRTRYFTLSGAQLSYRGGKSK--PDAPPIELSKIRSVKVVRK--KDRSIPKAFEIFTDDK 76

                         90       100
                 ....*....|....*....|....*....
gi 767927532 751 TYVFKAKDEKNAEEWLQCINVAVAQAKER 779
Cdd:cd01264   77 TYVLKAKDEKNAEEWLQCLSIAVAQAHAR 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 767927532 674 IEGKLKEKqvRWKFIKRWKTRYFTLAGNQLLFQKGKSKDDPD-DCPIELSKVQSVKAVAKKRRdrslPRAFEIFT-DNKT 751
Cdd:cd00821    1 KEGYLLKR--GGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKpKGSIPLSGILEVEEVSPKER----PHCFELVTpDGRT 74

                         90
                 ....*....|....*...
gi 767927532 752 YVFKAKDEKNAEEWLQCI 769
Cdd:cd00821   75 YYLQADSEEERQEWLKAL 92

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 767927532 675 EGKLkEKQVRWkfIKRWKTRYFTLAGNQLLFQKGkSKDDPDDCP---IELSKVQSVKAVakkRRDRSLPRAFEIFTDNKT 751
Cdd:cd13276    2 AGWL-EKQGEF--IKTWRRRWFVLKQGKLFWFKE-PDVTPYSKPrgvIDLSKCLTVKSA---EDATNKENAFELSTPEET 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767927532 752 YVFKAKDEKNAEEWLQCINVAVAQAkereSREVT 785
Cdd:cd13276   75 FYFIADNEKEKEEWIGAIGRAIVKH----SRSVT 104

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 767927532 673 LIEGKLKEKQvrwKFIKRWKTRYFTLAGNQLLFQKgkskDDPDDCP---IELSKVQSVKAVAKKRRdrslPRAFEIFTDN 749
Cdd:cd13298    7 LKSGYLLKRS---RKTKNWKKRWVVLRPCQLSYYK----DEKEYKLrrvINLSELLAVAPLKDKKR----KNVFGIYTPS 75

                         90       100
                 ....*....|....*....|.
gi 767927532 750 KTYVFKAKDEKNAEEWLQCIN 770
Cdd:cd13298   76 KNLHFRATSEKDANEWVEALR 96

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 767927532 668 QDGQPLIEGKLKEKQ--VRwkfiKRWKTRYFTLAGNQLLFQKgkSKDDPDdcPIELSKVQSVKAVAKKRRDRSLPR--AF 743
Cdd:cd13271    3 RAGRNVIKSGYCVKQgaVR----KNWKRRFFILDDNTISYYK--SETDKE--PLRTIPLREVLKVHECLVKSLLMRdnLF 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 767927532 744 EIFTDNKTYVFKAKDEKNAEEWLQCINVAVaQAKERESRE 783
Cdd:cd13271   75 EIITTSRTFYIQADSPEEMHSWIKAISGAI-VARRGPSRS 113

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 767927532 657 CNNPEKATVVNQdgQPLIEGKLKEKQVR-WKFIKRWKTRYFTLAGNQLLFQKgksKDDPDDC--PI-----ELSKVQsvk 728
Cdd:cd13258    3 FNEKELAALSSQ--PAEKEGKIAERQMGgPKKSEVFKERWFKLKGNLLFYFR---TNEFGDCsePIgaivlENCRVQ--- 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 767927532 729 avakKRRDRSLPRAFEI-FTDN--KTYVFKAKDEKNAEEWLQCI 769
Cdd:cd13258   75 ----MEEITEKPFAFSIvFNDEpeKKYIFSCRSEEQCEQWIEAL 114

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. 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 767927532 685 WK---FIKRWKTRYFTLAGN--QLLFQKGKSKDDPDDCpIELSKVQSVK------AVAKKRRDRSLpraFEIFTDNKTYV 753
Cdd:cd01235   10 YKrgaLLKGWKQRWFVLDSTkhQLRYYESREDTKCKGF-IDLAEVESVTpatpiiGAPKRADEGAF---FDLKTNKRVYN 85

                         90
                 ....*....|....*..
gi 767927532 754 FKAKDEKNAEEWLQCIN 770
Cdd:cd01235   86 FCAFDAESAQQWIEKIQ 102

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 767927532 688 IKRWKTRYFTLAGNQLLFQKgkSKDDPDDCP---IELSkvqSVKAVAKKRRDRSlpraFEIFTDNKTYVFKAKDEKNAEE 764
Cdd:cd13282   12 VKTWKRRWFVLKNGELFYYK--SPNDVIRKPqgqIALD---GSCEIARAEGAQT----FEIVTEKRTYYLTADSENDLDE 82

                         90
                 ....*....|....
gi 767927532 765 WLQCI-NVAVAQAK 777
Cdd:cd13282   83 WIRVIqNVLRRQAS 96

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. 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 767927532 688 IKRWKTRYFTLAGNQLLFQKGKSKDDPDdcP---IELSK-VQSVKAVAKKRRdrslpraFEIFTDNKTYVFKAKDEKNAE 763
Cdd:cd01265   16 LKGWKRRWFVLDESKCQLYYYRSPQDAT--PlgsIDLSGaAFSYDPEAEPGQ-------FEIHTPGRVHILKASTRQAML 86

                         90       100
                 ....*....|....*....|
gi 767927532 764 EWLQcinvaVAQAKERESRE 783
Cdd:cd01265   87 YWLQ-----ALQSKRREYCN 101

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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 767927532 689 KRWKTRYFTLAGNQLLFQKGKSKDDPDDCpIELSKVQSVKAVAKKRRDRSLpraFEIFTDNKTYVFKAKDEKNAEEWLQC 768
Cdd:cd13273   22 PTWTERWFVLKPNSLSYYKSEDLKEKKGE-IALDSNCCVESLPDREGKKCR---FLVKTPDKTYELSASDHKTRQEWIAA 97

                         90
                 ....*....|...
gi 767927532 769 INVAVAQAKERES 781
Cdd:cd13273   98 IQTAIRLSQEGKS 110

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. 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 767927532 685 WKFiKRWKTRYFTLAGNQLLFQKGKSKDDPDDcpIELSKVQSVKAVAKkrrdrSLPRAFEIFTDNKTYVFKAKDEKNAEE 764
Cdd:cd13274   11 SSF-QRWKRRYFKLKGRKLYYAKDSKSLIFEE--IDLSDASVAECSTK-----NVNNSFTVITPFRKLILCAESRKEMEE 82

                 ....*.
gi 767927532 765 WLQCIN 770
Cdd:cd13274   83 WISALK 88

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767927532 689 KRWKTRYFTLAGNQLLFQKGKSKDDPDDCpIELSKVQSVKAVAKKRrdrslpraFEIFTDNKTYVFKAKDEKNAEEWLQC 768
Cdd:cd13253   16 KGFQKRWVVFDGLSLRYFDSEKDAYSKRI-IPLSAISTVRAVGDNK--------FELVTTNRTFVFRAESDDERNLWCST 86

                 ....*..
gi 767927532 769 INVAVAQ 775
Cdd:cd13253   87 LQAAISE 93

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 767927532 689 KR-WKTRYFTLAGNQLLFQKGKSK-------DDPDDCpIELSKVQSVKAVAKKRRdrslPRAFEIFT-DNKTYVFKAKDE 759
Cdd:cd13295   29 KRgWKMFYATLKGLVLYLHKDEYGckkalryESLRNA-ISVHHSLATKATDYTKK----PHVFRLRTaDWREYLFQASDT 103

                         90
                 ....*....|....*
gi 767927532 760 KNAEEWLQCINVAVA 774
Cdd:cd13295  104 KEMQSWIEAINLVAA 118