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Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
PI3 Kinase 110 alpha bound to the inhibitor PIK-93 (yellow).
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols PIK3CA ; CLOVE; CWS5; MCAP; MCM; MCMTC; PI3K; p110-alpha
External IDs OMIM171834 MGI1206581 HomoloGene21249 IUPHAR: 2153 ChEMBL: 4005 GeneCards: PIK3CA Gene
EC number,
RNA expression pattern
PBB GE PIK3CA 204369 at tn.png
More reference expression data
Species Human Mouse
Entrez 5290 18706
Ensembl ENSG00000121879 ENSMUSG00000027665
UniProt P42336 P42337
RefSeq (mRNA) NM_006218 NM_008839
RefSeq (protein) NP_006209 NP_032865
Location (UCSC) Chr 3:
179.15 – 179.24 Mb
Chr 3:
32.4 – 32.47 Mb
PubMed search [1] [2]

The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (the HUGO-approved official symbol = PIK3CA; HGNC ID, HGNC:8975), also called p110α protein, is a class I PI 3-kinase catalytic subunit. The human p110α protein is encoded by the PIK3CA gene.[1]


Phosphatidylinositol-4,5-bisphosphate 3-kinase (also called phosphatidylinositol 3-kinase) is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate phosphatidylinositols (PtdIns), PtdIns4P and PtdIns(4,5)P2.[2]

Clinical significance[edit]

Recent evidence has shown that the PIK3CA gene is mutated in a range of human cancers. It has been found to be oncogenic and has been implicated in cervical cancers.[3]

Due to the association between p110α and cancer,[4] it is believed to be a promising drug target. A number of pharmaceutical companies are currently designing and charactering potential p110α isoform specific inhibitors.[5][6] The presence of PIK3CA mutation may predict response to aspirin therapy for colorectal cancer,[7][8] indicating power and promise of "Molecular Pathological Epidemiology (MPE)" approach[9] as well as a complex interaction within the tumor microenvironment in this phenomenon.[10]

Somatic mosaic mutations in PIK3CA have been implicated in several overgrowth conditions: CLOVES syndrome,[11] macrocephaly-capillary malformation syndrome,[12] hemimegalencephaly[13] and overgrowth with fibroadipose hyperplasia.[14]

See also[edit]


P110α has been shown to interact with:


  1. ^ Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF (August 1992). "Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit". Cell 70 (3): 419–29. doi:10.1016/0092-8674(92)90166-A. PMID 1322797. 
  2. ^ "Entrez Gene: PIK3CA". 
  3. ^ Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY (May 2000). "PIK3CA as an oncogene in cervical cancer". Oncogene 19 (23): 2739–44. doi:10.1038/sj.onc.1203597. PMID 10851074. 
  4. ^ Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (April 2004). "High frequency of mutations of the PIK3CA gene in human cancers". Science 304 (5670): 554. doi:10.1126/science.1096502. PMID 15016963. 
  5. ^ Stein RC (September 2001). "Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment". Endocrine-related Cancer (Bioscientifica) 8 (3): 237–48. doi:10.1677/erc.0.0080237. PMID 11566615. 
  6. ^ Marone R, Cmiljanovic V, Giese B, Wymann MP (January 2008). "Targeting phosphoinositide 3-kinase: moving towards therapy". Biochimica et Biophysica Acta 1784 (1): 159–85. doi:10.1016/j.bbapap.2007.10.003. PMID 17997386. 
  7. ^ Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S (2012). "Aspirin use, tumor PIK3CA mutation status, and colorectal cancer survival". N Engl J Med 367: 1596–606. doi:10.1056/nejmoa1207756. PMID 23094721. 
  8. ^ Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson IP, Midgley R (2013). "Evaluation of PIK3CA mutation as a predictor of benefit from NSAID therapy in colorectal cancer". J Clin Oncol 31: 4297–305. doi:10.1200/jco.2013.50.0322. PMID 24062397. 
  9. ^ Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT. "Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene 2013; doi:10.1038/onc.2013.244
  10. ^ Fuchs CS, Ogino S (2013). "Aspirin therapy for colorectal cancer with PIK3CA mutation: simply complex!". J Clin Oncol 31: 4358–61. doi:10.1200/jco.2013.52.0080. PMID 24166520. 
  11. ^ Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, et al. (Jun 2012). "Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome". Am J Hum Genet 90 (6): 1108–15. doi:10.1016/j.ajhg.2012.05.006. PMC 3370283. PMID 22658544. 
  12. ^ Rivière JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, et al. (2012). "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes". Nat Genet 44 (8): 934–40. doi:10.1038/ng.2331. PMC 3408813. PMID 22729224. 
  13. ^ Lee JH, Huynh M, Silhavy JL, Kim S, Dixon-Salazar T, Heiberg A, Scott E, Bafna V, et al. (2012). "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly". Nat Genet 44 (8): 941–5. doi:10.1038/ng.2329. PMID 22729223. 
  14. ^ Lindhurst MJ, Parker VE, Payne F, Sapp JC, Rudge S, Harris J, Witkowski AM, Zhang Q, et al. (2012). "Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA". Nat Genet 44 (8): 928–33. doi:10.1038/ng.2332. PMC 3461408. PMID 22729222. 
  15. ^ Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB (2003). "Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement". J. Biol. Chem. 278 (31): 28793–8. doi:10.1074/jbc.M303900200. PMID 12754211. 
  16. ^ Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochem. Biophys. Res. Commun. 307 (3): 459–65. doi:10.1016/s0006-291x(03)01187-2. PMID 12893243. 
  17. ^ Luo B, Prescott SM, Topham MK (2003). "Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta". J. Biol. Chem. 278 (41): 39542–7. doi:10.1074/jbc.M307153200. PMID 12890670. 
  18. ^ Vargiu P, De Abajo R, Garcia-Ranea JA, Valencia A, Santisteban P, Crespo P, Bernal J (2004). "The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors". Oncogene 23 (2): 559–68. doi:10.1038/sj.onc.1207161. PMID 14724584. 
  19. ^ Li W, Han M, Guan KL (2000). "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf". Genes Dev. 14 (8): 895–900. PMC 316541. PMID 10783161. 
  20. ^ Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J (1996). "Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation". EMBO J. 15 (10): 2442–51. PMC 450176. PMID 8665852. 
  21. ^ Sade H, Krishna S, Sarin A (2004). "The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells". J. Biol. Chem. 279 (4): 2937–44. doi:10.1074/jbc.M309924200. PMID 14583609. 
  22. ^ Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE (1993). "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. PMC 364842. PMID 8246987. 

Further reading[edit]