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Peripheral membrane proteins are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins.
Phosphatidylinositol consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecules the isomer of the inositol group is assumed to be the myo- conformer unless otherwise stated. Typically phosphatidylinositols form a minor component on the cytosolic side of eukaryotic cell membranes. The phosphate group gives the molecules a negative charge at physiological pH.
Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.
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.
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.
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins.
Phosphatidylinositol 3-phosphate (PtdIns3P) 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 activity on phosphatidylinositol.
Pleckstrin homology domain or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.
Phosphatidylinositol 3,5-bisphosphate 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 levels, and more than 100-fold lower than the abundant PtdIns4P and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock. The response to hyperosmotic challenge is not conserved in most tested mammalian cells except for differentiated 3T3L1 adipocytes.
Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene.
PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.
Oxysterol-binding protein 1 is a protein that in humans is encoded by the OSBP gene.
Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene.
Pleckstrin homology domain-containing family A member 1 is a protein that in humans is encoded by the PLEKHA1 gene.
Zinc finger FYVE domain-containing protein 1 is a protein that in humans is encoded by the ZFYVE1 gene.
Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes.
Sec14 is a cytosolic protein found in yeast which plays a role in the regulation of several cellular functions, specifically those related to intracellular transport. Encoded by the Sec14 gene, Sec14p may transport phosphatidylinosol and phosphatidylcholine produced in the endoplasmic reticulum and the Golgi body to other cellular membranes. Additionally, Sec14p potentially plays a role in the localization of lipid raft proteins. Sec14p is an essential gene in yeast, and is homologous in function to phosphatidylinositol transfer protein in mammals. A conditional mutant with non-functional Sec14p presents with Berkeley bodies and deficiencies in protein secretion.
Leonard (Len) R Stephens FRS is a molecular biologist, senior group leader and associate director at the Babraham Institute.
Phillip (Phill) Thomas Hawkins FRS is a molecular biologist, senior group leader at the Babraham Institute.
Pleckstrin homology domain containing A8 is a protein that in humans is encoded by the PLEKHA8 gene.
References
- ↑ Godi A et al., FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nat. Cell Biol. 2004 May;6(5):393-404.
- ↑ Choudhury RR, Hyvola N, Lowe M. Phosphoinositides and membrane traffic at the trans-Golgi network. Biochem Soc Symp. 2005;(72):31-8.
- ↑ Furse, Samuel; Brooks, Nicholas J.; Seddon, Annela M.; Woscholski, Rüdiger; Templer, Richard H.; Gaffney, Piers R. J.; Ces, Oscar (2012). "Lipid Membrane Curvature Induced by Distearoyl Phosphatidylinositol 4-Phosphate". Soft Matter. 8 (11): 3090–3093. doi:10.1039/c2sm07358g.
- ↑ Furse, Samuel; Brooks, Nicholas J.; Woscholski, Rüdiger; Gaffney, Piers R. J.; Templer, Richard H. (2016). "Pressure-dependent inverse bicontinuous cubic phase formation in a phosphatidylinositol 4-phosphate/phosphatidylcholine system". Chemical Data Collections. 3–4: 15–20. doi:10.1016/j.cdc.2016.08.001. hdl: 10044/1/42515 .
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