PI4KA

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	Wikidata
View/Edit Human

Phosphatidylinositol 4-kinase alpha is an enzyme that in humans is encoded by the PI4KA gene.^[1]^[2]^[3]

Function[edit | edit source]

This gene encodes a 1-phosphatidylinositol 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. Two transcript variants encoding different isoforms have been described for this gene.^[3]

Clinical significance[edit | edit source]

The alpha isoform of PI4KIII plays a role in replication of hepatitis C virus (HCV).^[4] Furthermore, the PI4KA lipid kinase affects HCV replication by altering phosphorylation of the HCV NS5A protein.^[5]

References[edit | edit source]

↑ Wong K, Cantley LC (Dec 1994). "Cloning and characterization of a human phosphatidylinositol 4-kinase". J Biol Chem. 269 (46): 28878–84. PMID 7961848.
↑ Nakagawa T, Goto K, Kondo H (Aug 1996). "Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase". J Biol Chem. 271 (20): 12088–94. doi:10.1074/jbc.271.20.12088. PMID 8662589.
↑ ^3.0 ^3.1 "Entrez Gene: PIK4CA phosphatidylinositol 4-kinase, catalytic, alpha polypeptide".
↑ Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R (January 2011). "Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment". Cell Host Microbe. 9 (1): 32–45. doi:10.1016/j.chom.2010.12.002. PMC 3433060. PMID 21238945.
↑ Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V (May 2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLoS Pathog. 9 (5): e1003359. doi:10.1371/journal.ppat.1003359. PMC 3649985. PMID 23675303.

Further reading[edit | edit source]

Gehrmann T, Heilmeyer LM (1998). "Phosphatidylinositol 4-kinases". Eur. J. Biochem. 253 (2): 357–70. doi:10.1046/j.1432-1327.1998.2530357.x. PMID 9654085.
Graziani A, Ling LE, Endemann G, et al. (1992). "Purification and characterization of human erythrocyte phosphatidylinositol 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate 4-kinase are distinct enzymes". Biochem. J. 284 (Pt 1): 39–45. PMC 1132694. PMID 1318025.
Kauffmann-Zeh A, Thomas GM, Ball A, et al. (1995). "Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling". Science. 268 (5214): 1188–90. doi:10.1126/science.7761838. PMID 7761838.
Prasad KV, Kapeller R, Janssen O, et al. (1994). "Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". Mol. Cell. Biol. 13 (12): 7708–17. doi:10.1128/mcb.13.12.7708. PMC 364842. PMID 8246987.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Berditchevski F, Chang S, Bodorova J, Hemler ME (1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". J. Biol. Chem. 272 (46): 29174–80. doi:10.1074/jbc.272.46.29174. PMID 9360995.
Gehrmann T, Gülkan H, Suer S, et al. (1999). "Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230". Biochim. Biophys. Acta. 1437 (3): 341–56. doi:10.1016/s1388-1981(99)00029-3. PMID 10101268.
Huang C, Handlogten ME, Miller RT (2002). "Parallel activation of phosphatidylinositol 4-kinase and phospholipase C by the extracellular calcium-sensing receptor". J. Biol. Chem. 277 (23): 20293–300. doi:10.1074/jbc.M200831200. PMID 11907035.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Subrahmanyam G, Rudd CE, Schneider H (2003). "Association of T cell antigen CD7 with type II phosphatidylinositol-4 kinase, a key component in pathways of inositol phosphate turnover". Eur. J. Immunol. 33 (1): 46–52. doi:10.1002/immu.200390006. PMID 12594831.
Carloni V, Mazzocca A, Ravichandran KS (2004). "Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc in liver tumor cells". Oncogene. 23 (8): 1566–74. doi:10.1038/sj.onc.1207287. PMID 14676841.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ahn J, Chung KS, Kim DU, et al. (2005). "Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus". J. Biochem. Mol. Biol. 37 (6): 741–8. doi:10.5483/bmbrep.2004.37.6.741. PMID 15607035.
Weixel KM, Blumental-Perry A, Watkins SC, et al. (2005). "Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases". J. Biol. Chem. 280 (11): 10501–8. doi:10.1074/jbc.M414304200. PMID 15634669.
Israels SJ, McMillan-Ward EM (2005). "CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen". Thromb. Haemost. 93 (2): 311–8. doi:10.1160/TH04-08-0503. PMID 15711748.
Waugh MG, Minogue S, Chotai D, et al. (2006). "Lipid and peptide control of phosphatidylinositol 4-kinase IIalpha activity on Golgi-endosomal Rafts". J. Biol. Chem. 281 (7): 3757–63. doi:10.1074/jbc.M506527200. PMID 16249177.
Israels SJ, McMillan-Ward EM (2005). "CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen". Thromb. Haemost. 93 (2): 311–8. doi:10.1160/TH04-08-0503. PMID 15711748.
Reiss S, et al. (2011). "Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment". Cell Host Microbe. 9 (1): 32–45. doi:10.1016/j.chom.2010.12.002. PMC 3433060. PMID 21238945.
Reiss S, et al. (2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLoS Pathog. 9 (5): e1003359. doi:10.1371/journal.ppat.1003359. PMC 3649985. PMID 23675303.

[pmid7961848-1] Wong K, Cantley LC (Dec 1994). "Cloning and characterization of a human phosphatidylinositol 4-kinase". J Biol Chem. 269 (46): 28878–84. PMID 7961848.

[pmid8662589-2] Nakagawa T, Goto K, Kondo H (Aug 1996). "Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase". J Biol Chem. 271 (20): 12088–94. doi:10.1074/jbc.271.20.12088. PMID 8662589.

[entrez-3] 3.0 ^3.1 "Entrez Gene: PIK4CA phosphatidylinositol 4-kinase, catalytic, alpha polypeptide".

[pmid21238945-4] Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R (January 2011). "Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment". Cell Host Microbe. 9 (1): 32–45. doi:10.1016/j.chom.2010.12.002. PMC 3433060. PMID 21238945.

[pmid23675303-5] Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V (May 2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLoS Pathog. 9 (5): e1003359. doi:10.1371/journal.ppat.1003359. PMC 3649985. PMID 23675303.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)