.. _PIK3C2A: PIK3C2A ^^^^^^^ .. contents:: :local: General Information ******************* :Full gene name: phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha :Entrez Gene ID: 5286 :Location: 11p15.5-p14 :Synonyms: CPK, PI3-K-C2(ALPHA), PI3-K-C2A :Type: protein-coding User SNPs ********* SNPs given by the user that are near or inside this gene: +--------+---------------+-----------+ | SNP | Distance (bp) | Direction | +========+===============+===========+ | rs5215 | 217276 | upstream | +--------+---------------+-----------+ .. _PIK3C2A Gene summary: NCBI Summary ************ 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 PI3-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 wortmanin. This protein was shown to be able to be activated by \ ``insulin``\ and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008] .. _OMIM ID 603601 : http://omim.org/entry/603601 .. _PIK3C2A OMIM Text: OMIM **** :OMIM ID: `OMIM ID 603601 `_ .. _PIK3C2A Phenotype: NCBI Phenotypes *************** * Genome-wide association study identifies five new schizophrenia loci. * NHGRI GWA Catalog .. _PIK3C2A GO Term: Gene Ontology ************* * Golgi apparatus * cytoplasm * vascular smooth muscle contraction * phosphatidylinositol 3-kinase activity * endocytosis * platelet-derived growth factor receptor signaling pathway * plasma membrane * epidermal growth factor receptor signaling pathway * phosphatidylinositol-3-phosphate biosynthetic process * ATP binding * phosphatidylinositol-mediated signaling * vesicle * nucleus * phosphatidylinositol phosphorylation * exocytosis * clathrin coat assembly * 1-phosphatidylinositol-4-phosphate 3-kinase activity * 1-phosphatidylinositol-3-kinase activity * phosphatidylinositol binding * phosphatidylinositol biosynthetic process * \ ``insulin``\ receptor signaling pathway * clathrin-coated vesicle .. _PIK3C2A Pathway: KEGG Pathways ************* * `Phosphatidylinositol signaling system `_ * `Metabolic pathways `_ * `Inositol phosphate metabolism `_ .. _PIK3C2A GeneRIF: GeneRIFs ******** * PI3-kinase activation induced by HIV-1 gp160 leads to downregulation of LFA-1-mediated T cell adhesion to B cells [`PMID 9341793`_] * Lowering the levels of PI3K-C2alpha in a number of cancer cell lines reduces their proliferation and cell viability. [`PMID 18403640`_] * CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway [`PMID 16524887`_] * Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) [`PMID 20379614`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Affinity Capture-MS [`PMID 20562859`_] * Phosphoinositide 3-kinase C2alpha was found to be differentially regulated by alpha(v)beta(3) and alpha(v)beta(5) integrin, and may represent a new regulatory pathway of cell migration downstream of integrin engagement. [`PMID 12237112`_] * HIV-1 Tat-mediated cytopathic changes in human brain microvascular endothelial cells involves its interaction with phosphatidylinositol 3-kinase (PI3K) [`PMID 14602571`_] * HIV-1 gp160 disrupts the association between phospholipase C gamma-1 and phosphoinositide 3 kinase (PI3-kinase), and this effect is dependent on PI3-kinase activity [`PMID 9808187`_] * Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator) [`PMID 20197460`_] * Affinity Capture-MS [`PMID 21906983`_] * Affinity Capture-MS [`PMID 17620599`_] * Affinity Capture-MS [`PMID 17620599`_] * molecular linkage between PI3K-C2alpha and the microtubule motor machinery, with implications for membrane trafficking in intact cells [`PMID 17110375`_] * Pro-survival effects of intracellular HIV-1 Tat in a microglial cell line is attributed to activation of the PI-3-kinase (PI3K)/Akt pathway via decreasing expression of PTEN, a negative regulator of the PI-3-K pathway [`PMID 17157319`_] * HIV-1 Tat activates phosphatidylinositol 3-kinase (PI3K), leading to the activation of Akt/PKB, decreased levels of cAMP and CREB phosphorylation, and the protection of cells from apoptosis [`PMID 17157319`_] * HIV-1 Tat induced release of MCP-1 from human lung microvascular endothelial cells involves an interaction between Tat and PI3 kinase [`PMID 11154208`_] * Nickel compounds induce HIF-1 transactivation and Cap43 protein expression through a PI-3K/Akt-dependent and p70(S6k)- independent pathway. [`PMID 14729612`_] * Affinity Capture-MS [`PMID 19615732`_] * Affinity Capture-MS [`PMID 17148452`_] * Affinity Capture-Western [`PMID 17148452`_] * Affinity Capture-MS [`PMID 17148452`_] * Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways [`PMID 15689238`_] * analysis of the PI specificities of PX domains and the mechanism by which the PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)-containing membranes [`PMID 17038310`_] * Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2alpha can modulate hepatocellular carcinoma cell growth. [`PMID 19591801`_] * VEGFR1 and VEGFR2 initiate a clonogenic response in myeloid leukemia cells that is PI3-kinase dependent. [`PMID 15183893`_] * Activation of protein kinase C-epsilon by HIV-1 Tat involves an interaction with PI 3-kinase [`PMID 9446795`_] * HIV-1 gp120-induced TNF-alpha production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways [`PMID 16081599`_] * HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors [`PMID 12960231`_] * demonstrated that the isolated clathrin binding domain of Phosphoinositide 3-kinase C2alpha can drive clathrin lattice assembly and can independently modulate clathrin distribution and function when expressed in cells [`PMID 16215232`_] * Phosphatidylinositol 3-kinase inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter by affecting the formation of the Tat-associated kinase transactivating complex [`PMID 12077252`_] * HIV-1 RT heterodimer expressed in bacteria can be phosphorylated in vitro by several purified mammalian protein kinases including auto-activated protein kinase (PK), CKII, cytosolic protamine kinase (CPK), myelin basic protein kinase 1 (MBPK1), and PRKC [`PMID 10641798`_] * These data suggest a general role for PI3KC2alpha in regulating physiologically relevant dynamin-independent internalization pathways. [`PMID 21081650`_] * Observational study of gene-disease association. (HuGE Navigator) [`PMID 20453000`_] * phosphoinositide 3-kinase C2alpha has a role in \ ``insulin``\ signaling [`PMID 17644513`_] .. _PMID 9341793: http://www.ncbi.nlm.nih.gov/pubmed/9341793 .. _PMID 18403640: http://www.ncbi.nlm.nih.gov/pubmed/18403640 .. _PMID 16524887: http://www.ncbi.nlm.nih.gov/pubmed/16524887 .. _PMID 20379614: http://www.ncbi.nlm.nih.gov/pubmed/20379614 .. _PMID 20562859: http://www.ncbi.nlm.nih.gov/pubmed/20562859 .. _PMID 12237112: http://www.ncbi.nlm.nih.gov/pubmed/12237112 .. _PMID 14602571: http://www.ncbi.nlm.nih.gov/pubmed/14602571 .. _PMID 9808187: http://www.ncbi.nlm.nih.gov/pubmed/9808187 .. _PMID 20197460: http://www.ncbi.nlm.nih.gov/pubmed/20197460 .. _PMID 21906983: http://www.ncbi.nlm.nih.gov/pubmed/21906983 .. _PMID 17620599: http://www.ncbi.nlm.nih.gov/pubmed/17620599 .. _PMID 17110375: http://www.ncbi.nlm.nih.gov/pubmed/17110375 .. _PMID 17157319: http://www.ncbi.nlm.nih.gov/pubmed/17157319 .. _PMID 11154208: http://www.ncbi.nlm.nih.gov/pubmed/11154208 .. _PMID 14729612: http://www.ncbi.nlm.nih.gov/pubmed/14729612 .. _PMID 19615732: http://www.ncbi.nlm.nih.gov/pubmed/19615732 .. _PMID 17148452: http://www.ncbi.nlm.nih.gov/pubmed/17148452 .. _PMID 15689238: http://www.ncbi.nlm.nih.gov/pubmed/15689238 .. _PMID 17038310: http://www.ncbi.nlm.nih.gov/pubmed/17038310 .. _PMID 19591801: http://www.ncbi.nlm.nih.gov/pubmed/19591801 .. _PMID 15183893: http://www.ncbi.nlm.nih.gov/pubmed/15183893 .. _PMID 9446795: http://www.ncbi.nlm.nih.gov/pubmed/9446795 .. _PMID 16081599: http://www.ncbi.nlm.nih.gov/pubmed/16081599 .. _PMID 12960231: http://www.ncbi.nlm.nih.gov/pubmed/12960231 .. _PMID 16215232: http://www.ncbi.nlm.nih.gov/pubmed/16215232 .. _PMID 12077252: http://www.ncbi.nlm.nih.gov/pubmed/12077252 .. _PMID 10641798: http://www.ncbi.nlm.nih.gov/pubmed/10641798 .. _PMID 21081650: http://www.ncbi.nlm.nih.gov/pubmed/21081650 .. _PMID 20453000: http://www.ncbi.nlm.nih.gov/pubmed/20453000 .. _PMID 17644513: http://www.ncbi.nlm.nih.gov/pubmed/17644513 .. _PIK3C2A Pubmed: PubMed Articles *************** *Recent articles:* * Kim W et al. "Systematic and quantitative assessment of the ubiquitin-modified proteome." Mol Cell. 2011 Oct 21;44(2):325-40. `PMID 21906983`_ * Wagner SA et al. "A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles." Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. `PMID 21890473`_ * Ripke S et al. "Genome-wide association study identifies five new schizophrenia loci." Nat Genet. 2011 Sep 18;43(10):969-76. `PMID 21926974`_ * Danielsen JM et al. "Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level." Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. `PMID 21139048`_ * Krag C et al. "PI3KC2α, a class II PI3K, is required for dynamin-independent internalization pathways." J Cell Sci. 2010 Dec 15;123(Pt 24):4240-50. `PMID 21081650`_ * Liu CY et al. "A Large-scale genetic association study of esophageal adenocarcinoma risk." Carcinogenesis. 2010 Jul;31(7):1259-63. `PMID 20453000`_ * Behrends C et al. "Network organization of the human autophagy system." Nature. 2010 Jul 1;466(7302):68-76. `PMID 20562859`_ * Kostakis GC et al. "Absence of hotspot mutations in exons 9 and 20 of the PIK3CA gene in human oral squamous cell carcinoma in the Greek population." Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 May;109(5):e53-8. `PMID 20416519`_ * Rose JE et al. "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score." Mol Med. 2010 Jul-Aug;16(7-8):247-53. `PMID 20379614`_ * Koutros S et al. "Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer." Cancer Res. 2010 Mar 15;70(6):2389-96. `PMID 20197460`_ .. _PMID 21890473: http://www.ncbi.nlm.nih.gov/pubmed/21890473 .. _PMID 20197460: http://www.ncbi.nlm.nih.gov/pubmed/20197460 .. _PMID 20416519: http://www.ncbi.nlm.nih.gov/pubmed/20416519 .. _PMID 21139048: http://www.ncbi.nlm.nih.gov/pubmed/21139048 .. _PMID 20379614: http://www.ncbi.nlm.nih.gov/pubmed/20379614 .. _PMID 21926974: http://www.ncbi.nlm.nih.gov/pubmed/21926974 .. _PMID 21081650: http://www.ncbi.nlm.nih.gov/pubmed/21081650 .. _PMID 20453000: http://www.ncbi.nlm.nih.gov/pubmed/20453000 .. _PMID 20562859: http://www.ncbi.nlm.nih.gov/pubmed/20562859 .. _PMID 21906983: http://www.ncbi.nlm.nih.gov/pubmed/21906983 *Top Pubmed articles linked to gene PIK3C2A matching any search term:* * Dominguez V et al. "Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells." J Biol Chem. 2011 Feb 11;286(6):4216-25. `PMID 21127054`_ * Koutros S et al. "Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer." Cancer Res. 2010 Mar 15;70(6):2389-96. `PMID 20197460`_ * Falasca M et al. "The role of phosphoinositide 3-kinase C2alpha in insulin signaling." J Biol Chem. 2007 Sep 21;282(38):28226-36. `PMID 17644513`_ * Kwintkiewicz J et al. "Insulin and oxidative stress modulate proliferation of rat ovarian theca-interstitial cells through diverse signal transduction pathways." Biol Reprod. 2006 Jun;74(6):1034-40. `PMID 16481589`_ * Gaidarov I et al. "Individual phosphoinositide 3-kinase C2alpha domain activities independently regulate clathrin function." J Biol Chem. 2005 Dec 9;280(49):40766-72. `PMID 16215232`_ * El Sheikh SS et al. "Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation." BMC Clin Pathol. 2003 Oct 16;3(1):4. `PMID 14563213`_ * Deregibus MC et al. "HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells." J Biol Chem. 2002 Jul 12;277(28):25195-202. `PMID 11994280`_ * Brown RA et al. "Insulin activates the alpha isoform of class II phosphoinositide 3-kinase." J Biol Chem. 1999 May 21;274(21):14529-32. `PMID 10329640`_ .. _PMID 20197460: http://www.ncbi.nlm.nih.gov/pubmed/20197460 .. _PMID 16215232: http://www.ncbi.nlm.nih.gov/pubmed/16215232 .. _PMID 21127054: http://www.ncbi.nlm.nih.gov/pubmed/21127054 .. _PMID 14563213: http://www.ncbi.nlm.nih.gov/pubmed/14563213 .. _PMID 10329640: http://www.ncbi.nlm.nih.gov/pubmed/10329640 .. _PMID 11994280: http://www.ncbi.nlm.nih.gov/pubmed/11994280 .. _PMID 17644513: http://www.ncbi.nlm.nih.gov/pubmed/17644513 .. _PMID 16481589: http://www.ncbi.nlm.nih.gov/pubmed/16481589