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Phosphatidylinositol 3-phosphate
Phosphatidylinositol 3-phosphate (PI3P) 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 phosphatase In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester, monoester into a phosphate ion and an Alcohol (chemistry), alcohol. Because a phosphatase enzyme catalysis, catalyzes the hydrolysis of its Substrate ...s, 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 domains – 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, PIK3C3 ...
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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 w ...
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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; SNAG1; SNX9 Sorti ...
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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 * * * EC 2.7.1 {{Cell-biology-stub ...
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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 has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei .... 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 int ...
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EEA1
The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1. EEA1 localizes exclusively to early endosomes and has an important role in endosomal trafficking. EEA1 binds directly to the phospholipid phosphatidylinositol 3-phosphate through its C-terminal FYVE domain and forms a homodimer through a coiled coil. EEA1 acts as a tethering molecule that couples vesicle docking with SNARE (protein), SNAREs such as N-ethylmaleimide sensitive fusion protein, bringing the endosomes physically closer and ultimately resulting in the fusion and delivery of endosomal cargo. Function EEA1 is a RAB5A effector protein which binds via an N-terminal zinc finger domain and is required for fusion of early and late endosomes and for sorting at the early endosome level. EEA1 plays a role in endocytosis and is recruited by Rab5-GTP to endosomal membranes. EEA1 may be regulated through monoubiquination, affecting endosome fusion and trafficking. Ubiquitin selective segregase p97 m ...
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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 * TSG101 Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name. Function The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enz .... 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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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 that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...s. This protein may form oligomeric complexes with other family members. References Further reading * * * * * * * * * * * * * * * * * * * Externa ...
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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 The PHD finger was discovered in 1993 as a Cys ...
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Cell Membranes
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell 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 a cell, being selectively permeable to ions and organic molecule ...
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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, ...
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