PIK3C2A

PIK3C2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AR5, 2IWL, 2REA, 2RED
Identifiers
Aliases	PIK3C2A , CPK, PI3-K-C2(ALPHA), PI3-K-C2A, PI3K-C2-alpha, PI3K-C2alpha, phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha, OCSKD
External IDs	OMIM: 603601 MGI: 1203729 HomoloGene: 20581 GeneCards: PIK3C2A
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11p15.1 Start 17,077,730 bp [1] End 17,207,986 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 F1|7 61.62 cM Start 115,936,500 bp [2] End 116,042,684 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte jejunal mucosa superficial temporal artery retinal pigment epithelium caput epididymis visceral pleura corpus epididymis lower lobe of lung seminal vesicula external globus pallidus Top expressed in medullary collecting duct seminal vesicula iris vas deferens ciliary body uterus renal corpuscle Paneth cell maxillary prominence epithelium of stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding 1-phosphatidylinositol-3-kinase activity 1-phosphatidylinositol-4-phosphate 3-kinase activity kinase activity phosphatidylinositol binding phosphatidylinositol 3-kinase activity ATP binding Cellular component cytoplasm vesicle cytosol phosphatidylinositol 3-kinase complex Golgi apparatus membrane plasma membrane extracellular exosome cytoplasmic vesicle clathrin-coated vesicle nucleus Biological process insulin receptor signaling pathway endocytosis epidermal growth factor receptor signaling pathway phosphorylation phosphatidylinositol phosphate biosynthetic process clathrin coat assembly phosphatidylinositol biosynthetic process platelet-derived growth factor receptor signaling pathway phosphatidylinositol-mediated signaling vascular associated smooth muscle contraction exocytosis phosphatidylinositol-3-phosphate biosynthetic process membrane organization phosphatidylinositol 3-kinase signaling cell migration positive regulation of cell migration involved in sprouting angiogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5286 18704 Ensembl ENSG00000011405 ENSMUSG00000030660 UniProt O00443 Q61194 RefSeq (mRNA) NM_002645 NM_001321378 NM_001321380 NM_001386870 NM_011083 RefSeq (protein) NP_001308307 NP_001308309 NP_002636 NP_035213 Location (UCSC) Chr 11: 17.08 – 17.21 Mb Chr 7: 115.94 – 116.04 Mb PubMed search [3] [4]
Wikidata
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Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide is an enzyme that in humans is encoded by the PIK3C2A gene. ^{[5] [6]}

The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking.

This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of Class II PI 3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmannin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. ^[6]

Clinical significance

Three families have been reported with homozygous loss of function mutations in this gene. ^[7] The clinical features of this syndrome include short stature, coarse facial features, cataracts with secondary glaucoma, multiple skeletal abnormalities and neurological manifestations. Abnormalities of cilial function were also noted.

References

1. GRCh38: Ensembl release 89: ENSG00000011405 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030660 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Domin J, Pages F, Volinia S, Rittenhouse SE, Zvelebil MJ, Stein RC, Waterfield MD (Nov 1997). "Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin". Biochem J. 326 (1): 139–47. doi:10.1042/bj3260139. PMC   1218647 . PMID   9337861.
6. "Entrez Gene: PIK3C2A phosphoinositide-3-kinase, class 2, alpha polypeptide".
7. Tiosano D, Baris HN, Chen A, Hitzert MM, Schueler M, Gulluni F, et al. (April 2019). "Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction". PLOS Genetics. 15 (4): e1008088. doi: 10.1371/journal.pgen.1008088 . PMC   6508738 . PMID   31034465.

Further reading

• Lee C, Liu QH, Tomkowicz B, et al. (2004). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways". J. Leukoc. Biol. 74 (5): 676–682. doi: 10.1189/jlb.0503206 . PMID   12960231. S2CID   11362623.
• Milani D, Mazzoni M, Borgatti P, et al. (1996). "Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells". J. Biol. Chem. 271 (38): 22961–22964. doi: 10.1074/jbc.271.38.22961 . PMID   8798481.
• Mazerolles F, Barbat C, Fischer A (1997). "Down-regulation of LFA-1-mediated T cell adhesion induced by the HIV envelope glycoprotein gp160 requires phosphatidylinositol-3-kinase activity". Eur. J. Immunol. 27 (9): 2457–2465. doi:10.1002/eji.1830270946. PMID   9341793. S2CID   33397908.
• Borgatti P, Zauli G, Colamussi ML, et al. (1998). "Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells". Eur. J. Immunol. 27 (11): 2805–2811. doi:10.1002/eji.1830271110. PMID   9394803. S2CID   6303471.
• Borgatti P, Zauli G, Cantley LC, Capitani S (1998). "Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta isoforms in PC12 cells". Biochem. Biophys. Res. Commun. 242 (2): 332–337. doi:10.1006/bbrc.1997.7877. PMID   9446795.
• Zhang J, Banfić H, Straforini F, et al. (1998). "A type II phosphoinositide 3-kinase is stimulated via activated integrin in platelets. A source of phosphatidylinositol 3-phosphate". J. Biol. Chem. 273 (23): 14081–14084. doi: 10.1074/jbc.273.23.14081 . PMID   9603905.
• Milani D, Mazzoni M, Zauli G, et al. (1998). "HIV-1 Tat induces tyrosine phosphorylation of p125FAK and its association with phosphoinositide 3-kinase in PC12 cells". AIDS. 12 (11): 1275–1284. doi: 10.1097/00002030-199811000-00008 . PMID   9708406. S2CID   25758704.
• Jauliac S, Mazerolles F, Jabado N, et al. (1998). "Ligands of CD4 inhibit the association of phospholipase Cgamma1 with phosphoinositide 3 kinase in T cells: regulation of this association by the phosphoinositide 3 kinase activity". Eur. J. Immunol. 28 (10): 3183–3191. doi: 10.1002/(SICI)1521-4141(199810)28:10<3183::AID-IMMU3183>3.0.CO;2-A . PMID   9808187.
• Brown RA, Domin J, Arcaro A, et al. (1999). "Insulin activates the alpha isoform of class II phosphoinositide 3-kinase". J. Biol. Chem. 274 (21): 14529–14532. doi: 10.1074/jbc.274.21.14529 . PMID   10329640.
• Idriss H, Kawa S, Damuni Z, et al. (2000). "HIV-1 reverse transcriptase is phosphorylated in vitro and in a cellular system". Int. J. Biochem. Cell Biol. 31 (12): 1443–1452. doi:10.1016/S1357-2725(99)00097-7. PMID   10641798.
• Domin J, Gaidarov I, Smith ME, et al. (2000). "The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles". J. Biol. Chem. 275 (16): 11943–11950. doi: 10.1074/jbc.275.16.11943 . PMID   10766823.
• Arcaro A, Zvelebil MJ, Wallasch C, et al. (2000). "Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors". Mol. Cell. Biol. 20 (11): 3817–3830. doi:10.1128/MCB.20.11.3817-3830.2000. PMC   85707 . PMID   10805725.
• Park IW, Wang JF, Groopman JE (2001). "HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes". Blood. 97 (2): 352–358. doi: 10.1182/blood.V97.2.352 . PMID   11154208.
• Zauli G, Milani D, Mirandola P, et al. (2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway". FASEB J. 15 (2): 483–491. doi: 10.1096/fj.00-0354com . PMID   11156964. S2CID   26315564.
• Gaidarov I, Smith ME, Domin J, Keen JH (2001). "The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking". Mol. Cell. 7 (2): 443–449. doi: 10.1016/S1097-2765(01)00191-5 . PMID   11239472.
• Caldwell GM, Eddy RL, Day CD, et al. (2001). "Mapping of genes and transcribed sequences in a gene rich 400-kb region on human chromosome 11p15.1→p14". Cytogenet. Cell Genet. 92 (1–2): 103–107. doi:10.1159/000056877. PMID   11306805. S2CID   46081338.
• Didichenko SA, Thelen M (2002). "Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles". J. Biol. Chem. 276 (51): 48135–42. doi: 10.1074/jbc.M104610200 . PMID   11606566.
• Deregibus MC, Cantaluppi V, Doublier S, et al. (2002). "HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells". J. Biol. Chem. 277 (28): 25195–25202. doi: 10.1074/jbc.M200921200 . PMID   11994280.
• Cook JA, August A, Henderson AJ (2002). "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 (1): 254–60. doi: 10.4049/jimmunol.169.1.254 . PMID   12077252.