P110α

This article relies excessively on references to primary sources. Please improve this article by adding secondary or tertiary sources. Find sources: "P110α" – news · newspapers · books · scholar · JSTOR (June 2016) (Learn how and when to remove this message)

PIK3CA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2ENQ, 2RD0, 3HHM, 3HIZ, 3ZIM, 4JPS, 4L1B, 4L23, 4L2Y, 4OVU, 4OVV, 4TUU, 4TV3, 4WAF, 4YKN, 5DXH, 5DXT, 5FI4, 4ZOP
Identifiers
Aliases	PIK3CA, CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, p110-alpha, PI3K-alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, CLAPO, CCM4
External IDs	OMIM: 171834; MGI: 1206581; HomoloGene: 21249; GeneCards: PIK3CA; OMA:PIK3CA - orthologs
EC number	2.7.11.1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q26.32 Start 179,148,114 bp[1] End 179,240,093 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 A3|3 15.7 cM Start 32,451,820 bp[2] End 32,522,635 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon gonad testicle tendon of biceps brachii ventricular zone secondary oocyte ganglionic eminence cartilage tissue right ventricle skin of hip Top expressed in Rostral migratory stream lacrimal gland iris mammillary body lobe of cerebellum lateral geniculate nucleus ascending aorta cerebellar vermis genital tubercle ciliary body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activator activity 1-phosphatidylinositol-4-phosphate 3-kinase activity protein serine/threonine kinase activity protein binding insulin receptor substrate binding ATP binding 1-phosphatidylinositol-3-kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity kinase activity phosphatidylinositol 3-kinase activity phosphatidylinositol-3,4-bisphosphate 5-kinase activity Cellular component phosphatidylinositol 3-kinase complex cytosol phosphatidylinositol 3-kinase complex, class IA plasma membrane lamellipodium cytoplasm membrane Biological process negative regulation of neuron apoptotic process cardiac muscle contraction epidermal growth factor receptor signaling pathway protein kinase B signaling Fc-gamma receptor signaling pathway involved in phagocytosis regulation of multicellular organism growth T cell costimulation hypomethylation of CpG island positive regulation of peptidyl-serine phosphorylation platelet activation Fc-epsilon receptor signaling pathway phosphatidylinositol phosphate biosynthetic process vascular endothelial growth factor receptor signaling pathway vasculature development angiogenesis insulin receptor signaling pathway via phosphatidylinositol 3-kinase glucose metabolic process phagocytosis energy homeostasis negative regulation of fibroblast apoptotic process regulation of gene expression liver development adipose tissue development regulation of cellular respiration T cell receptor signaling pathway activation of protein kinase activity regulation of genetic imprinting negative regulation of anoikis cellular response to glucose stimulus endothelial cell migration phosphatidylinositol-mediated signaling leukocyte migration ERBB2 signaling pathway phosphatidylinositol-3-phosphate biosynthetic process axon guidance negative regulation of macroautophagy phosphorylation positive regulation of TOR signaling anoikis adaptive immune response protein phosphorylation inflammatory response innate immune response cell chemotaxis G protein-coupled receptor signaling pathway positive regulation of protein kinase B signaling phosphatidylinositol 3-kinase signaling cytokine-mediated signaling pathway cell migration positive regulation of phosphatidylinositol 3-kinase signaling phosphatidylinositol biosynthetic process regulation of protein phosphorylation Sources:Amigo / QuickGO
Orthologs 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: 32.45 – 32.52 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5]

Its role was uncovered by molecular pathological epidemiology (MPE).^[6]

Phosphatidylinositol-4,5-bisphosphate 3-kinase (also called phosphatidylinositol 3-kinase (PI3K)) 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.^[7]

The involvement of p110α in human cancer has been hypothesized since 1995. Support for this hypothesis came from genetic and functional studies, including the discovery of common activating PIK3CA missense mutations in common human tumors.^[8] It has been found to be oncogenic and is implicated in cervical cancers.^[9] PIK3CA mutations are present in over one-third of breast cancers, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes (HER2 +). The three hotspot mutation positions (GLU542, GLU545, and HIS1047) have been widely reported till date.^[10] While substantial preclinical data show an association with robust activation of the pathway and resistance to common therapies, clinical data do not indicate that such mutations are associated with high levels of pathway activation or with a poor prognosis. It is unknown whether the mutation predicts increased sensitivity to agents targeting the P3K pathway.^[11]

PIK3CA participates in a complex interaction within the tumor microenvironment in this phenomenon.^[12]

Due to the association between p110α and cancer,^[13] it may be an appropriate drug target. Pharmaceutical companies are designing and characterizing potential p110α isoform specific inhibitors.^[14][15]

The presence of [a] PIK3CA mutation may predict response to aspirin therapy for colorectal cancer.^[16][17]

Somatic activating mutations in PIK3CA are found in Klippel–Trénaunay syndrome and venous malformation.^[18][19]

PIK3CA-associated segmental overgrowth includes brain disorders such as macrocephaly-capillary malformation (MCAP) and hemimegalencephaly. It is also associated with congenital, lipomatous overgrowth of vascular malformations, epidermal nevi and skeletal/spinal anomalies (CLOVES syndrome) and fibroadipose hyperplasia (FH). The conditions are caused by heterozygous (usually somatic mosaic) mutations.^[20]

All PI 3-kinases are inhibited by the drugs wortmannin and LY294002 but wortmannin shows better efficiency than LY294002 on the hotspot mutation positions.^[21][22]

In September 2017 Copanlisib, inhibiting predominantly p110α and p110δ, got FDA approval for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.^[23]

• Phosphoinositide 3-kinase
• Phosphoinositide 3-kinase inhibitor
• PIK3CA-related overgrowth spectrum

P110α has been shown to interact with: