PtdIns3P
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PtdIns3P
Phosphatidylinositol 3-phosphate (PtdIns3''P'') is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases (PI 3-kinases) activity on phosphatidylinositol. PtdIns3''P'' is dephosphorylated by the myotubularin family of phosphatases, on the D3 position of the inositol ring, and can be converted to PtdIns(3,5)''P''2 by the lipid kinase PIKfyve. Both FYVE domains and PX domain The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes. This domain was first found in P40phox and p47phox domains of NADPH oxidase (phox stands for phagocytic oxidase). It was also ident ...s – found in proteins such as SNX1, HGS, and EEA1 – bind to PtdIns3''P''. The majority of PtdIns3''P'' appears to be constitutively synthesised by the class III PI 3-kinase, ...
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Phosphatidylinositol 3,5-bisphosphate
Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P ( Phosphatidylinositol 5-phosphate) levels, and more than 100-fold lower than the abundant PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997.Whiteford CC, Brearley CA, Ulug ET. Phosphatidylinositol 3,5-bisphosphate defines a novel PI 3-kinase pathway in resting mouse fibroblasts. Biochem J. 1997 May 1;323 ( Pt 3):597-601. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock.Dove SK, Cooke FT, Douglas MR, Sayers LG, Parker PJ, Michell RH. Osmotic stress activates phosphatidylinositol-3,5 ...
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Phosphoinositide 3-kinases
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor gene PTEN, is implicated in the sensitivity of cancer tumors to insulin and IGF1, and in calorie restriction. Discovery The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had ...
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Phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typically have omega-3 fatty acids EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine. Phospholipids are a key component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. In eukaryotes, cell membranes also contain another class of lipid, sterol, interspersed among the phospholipids. The combination provides fluidity in two dimensions combined with mechanical strength against rupture. Purified phospholipids are produced commercially and have found applications in nanotechnology and materials science. The first phospholipid identified in 1847 as such in biological tissues wa ...
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SNX1
Sorting nexin-1 is a protein that in humans is encoded by the SNX1 gene. The protein encoded by this gene is a sorting nexin. SNX1 is a component of the retromer complex. Function This gene encodes a member of the sorting nexin family. Members of this family contain a phox ( PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane p ...s. This protein may form oligomeric complexes with other family members. References Further reading * * * * * * * * * * * * * * * * * * * External ...
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Class II PI 3-kinases
Class II PI 3-kinases are a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain structure, substrate specificity and method of activation. Class II PI 3-kinases were the most recently identified class of PI 3-kinases. There are three class II PI 3-kinase isoforms expressed in mammalian cells; *PI3K-C2α encoded by the PIK3C2A gene *PI3K-C2β encoded by the PIK3C2B gene *PI3K-C2γ encoded by the PIK3C2G gene See also * Phosphoinositide 3-kinase Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ... References *Stein RC (2001) Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment ''Endocr Relat Cancer'' 8:237-24*Foster FM, Traer CJ, Abraham SM, and Fry MJ (2003) The phosphoinositide (PI) 3-kinase family ''J Cell Sci'' 116:3037-3 ...
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PIK3C3
Phosphatidylinositol 3-kinase catalytic subunit type 3 is an enzyme subunit that in humans is encoded by the ''PIK3C3'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... It's a class III phosphoinositide 3-kinase. References Further reading

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Class III PI 3-kinase
Class III PI 3-kinase is a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain structure, substrate specificity and method of activation. There is only one known class III PI 3-kinase, Vps34, which is also the only PI 3-kinase expressed in all eukaryotic cells. In humans it is encoded by the PIK3C3 gene. In human cells Vps34 associates with a regulatory subunit, PIK3R4(p150, Vps15). Substrate specificity Vps34 is more accurately described as a phosphatidylinositol 3-kinase. ''In vivo'' Vps34 can phosphorylate only phosphatidylinositol to form phosphatidylinositol (3)-phosphate ( PtdIns(3)P). Functions Vps34 was first identified in a ''Saccharomyces cerevisiae'' (budding yeast) screen for proteins involved vesicle-mediated vacuolar protein sorting (hence Vps). A number of proteins containing a phosphoinositide binding domain specific for PtdIns(3)P that function in cellular protein trafficking have been identified. Vps34 has been shown to in ...
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HGS (gene)
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the ''HGS'' gene. Interactions HGS has been shown to interact with: * CLTC * DLG4, * EPS15, * IL2RB, * Merlin, * STAM2, * Signal transducing adaptor molecule Signal transducing adapter molecule 1 is a protein that in humans is encoded by the ''STAM'' gene. Function This gene was identified by the rapid tyrosine-phosphorylation of its product in response to cytokine stimulation. The encoded protein ... * TSG101. References External links PDBe-KBprovides an overview of all the structure information available in the PDB for Human Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) Further reading

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FYVE Domain
In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidylinositol 3-phosphate, in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH-dependent manner. The FYVE domain has been connected to vacuolar protein sorting and endosome function. Structure The FYVE domain is composed of two small beta hairpins (or zinc knuckles) followed by an alpha helix. The FYVE finger binds two zinc ions. The FYVE finger has eight potential zinc coordinating cysteine positions and is characterized by having basic amino acids around the cysteines. Many members of this family also include two histidines in a sequence motif: The FYVE finger is structurally similar to the RING domain and the PHD finger. Examples The following is a list of human p ...
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PX Domain
The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes. This domain was first found in P40phox and p47phox domains of NADPH oxidase (phox stands for phagocytic oxidase). It was also identified in many other proteins involved in membrane trafficking, including nexins, Phospholipase D, and phosphoinositide-3-kinases. The PX domain is structurally conserved in eukaryotes, although amino acid sequences show little similarity. PX domains interact primarily with PtdIns(3)P lipids. However some of them bind to phosphatidic acid, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns(4,5)P2, and PtdIns(3,4,5)P3. The PX-domain can also interact with other domains and proteins. Human proteins containing this domain Sorting nexins contain this domain. Other examples include: * HS1BP3 * KIF16B (SNX23) * NCF1; NCF1C; NCF4; NISCH * PIK3C2A; PIK3C2B; PIK3C2G; PLD1; PLD2; PXK * RPS6KC1 * SGK3; SH3PXD2A SH3 and PX domain-containing ...
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Cell Membranes
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to i ...
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