Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958805086  89 KSGTLYRLTVQNNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQR 168
Cdd:cd13327     1 KSGTLYRLTVQNNWKAFTFVLSRSYLMAFQPGCLDEDPLLSYNVDVCLAVQMDMLDGCDSCFQVIFPQDVLRLRAETRQR 80

                  ....*...
gi 1958805086 169 AQEWMEAL 176
Cdd:cd13327    81 AQEWMEAL 88

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 2; PLEKHM3 (also called differentiation associated protein/DAPR)(also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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 1958805086  89 KSGTLYRLTVQNNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQR 168
Cdd:cd13327     1 KSGTLYRLTVQNNWKAFTFVLSRSYLMAFQPGCLDEDPLLSYNVDVCLAVQMDMLDGCDSCFQVIFPQDVLRLRAETRQR 80

                  ....*...
gi 1958805086 169 AQEWMEAL 176
Cdd:cd13327    81 AQEWMEAL 88

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958805086   87 ILKSGTLYRLTVQNN--WKAFTFVLSKAYLMAF--HPGKLDEDPLLSYNVDVCLAVQTDNLDGCDS--CFQVIFPQ-DVL 159
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYksKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKphCFEIKTSDrKTL 80

                           90       100
                   ....*....|....*....|..
gi 1958805086  160 RLRAETRQRAQEWMEALKTAAN 181
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 2; PLEKHM3 (also called differentiation associated protein/DAPR)(also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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 1958805086  89 KSGTLYRLTVQNNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQR 168
Cdd:cd13327     1 KSGTLYRLTVQNNWKAFTFVLSRSYLMAFQPGCLDEDPLLSYNVDVCLAVQMDMLDGCDSCFQVIFPQDVLRLRAETRQR 80

                  ....*...
gi 1958805086 169 AQEWMEAL 176
Cdd:cd13327    81 AQEWMEAL 88

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958805086 101 NWKAFTFVLSKaYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQRAQEWMEALK 177
Cdd:cd10573    18 NWKTRWFVLRR-NELKYFKTRGDTKPIRVLDLRECSSVQRDYSQGKVNCFCLVFPERTFYMYANTEEEADEWVKLLK 93

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 1958805086  89 KSGTLYRLT--VQNNWKAFTFVLSKAYLMAF-HPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQD-VLRLRAE 164
Cdd:cd00821     1 KEGYLLKRGggGLKSWKKRWFVLFEGVLLYYkSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGrTYYLQAD 80

                          90
                  ....*....|..
gi 1958805086 165 TRQRAQEWMEAL 176
Cdd:cd00821    81 SEEERQEWLKAL 92

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958805086 100 NNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDgCDSCFQVIFPQDVLRLRAETRQRAQEWMEALKTA 179
Cdd:cd13250    14 KTWKRRWFSLQNGQLYYQKRDKKDEPTVMVEDLRLCTVKPTEDSD-RRFCFEVISPTKSYMLQAESEEDRQAWIQAIQSA 92

                  ....
gi 1958805086 180 ANAA 183
Cdd:cd13250    93 IASA 96

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958805086 132 VDVCLAvQTDNLDGCDScFQVIFPQDVLRLRAETRQRAQEWMEALKTAAN 181
Cdd:cd13274    45 SDASVA-ECSTKNVNNS-FTVITPFRKLILCAESRKEMEEWISALKTVQQ 92