PIK3C2A

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

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

OMIM ID:`OMIM ID 603601 `_

NCBI Phenotypes

• Genome-wide association study identifies five new schizophrenia loci.
• NHGRI GWA Catalog

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

KEGG Pathways

• Phosphatidylinositol signaling system
• Metabolic pathways
• Inositol phosphate metabolism

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]

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

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