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Gene Review

PIK3C3  -  phosphatidylinositol 3-kinase, catalytic...

Homo sapiens

Synonyms: PI3-kinase type 3, PI3K type 3, Phosphatidylinositol 3-kinase catalytic subunit type 3, Phosphatidylinositol 3-kinase p100 subunit, Phosphoinositide-3-kinase class 3, ...
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Disease relevance of PIK3C3

  • This study utilizes small interfering (si)RNA-mediated gene silencing to define the specific trafficking pathways in which hVps34 functions in human U-251 glioblastoma cells [1].

Psychiatry related information on PIK3C3


High impact information on PIK3C3

  • A new role for 3-phosphoinositides in the constitutive movement o f proteins from one intracellular compartment to another was proposed with the discovery of homology between the product of a yeast gene important for vacuolar sorting, Vps34p, and a mammalian PI 3-kinase [3].
  • Rab5 regulates the production of phosphatidylinositol 3-phosphate (PtdIns[3]P) through a dual mechanism, by directly phosphorylating phosphatidylinositol via Vps34 and by a hierarchical enzymatic cascade of phosphoinositide-3-kinasebeta (PI3Kbeta), PI 5-, and PI 4-phosphatases [4].
  • The demonstration that Vps34p (a protein required for targeting soluble hydrolases to the vacuole in Saccharomyces cerevisiae) is a phosphatidylinositol 3-kinase (PI3-K) suggested the possibility that a homologous enzyme might be involved in the equivalent step in mammalian cells [5].
  • Here the molecular characterization of a new human PtdIns 3-kinase with extensive sequence homology to Vps34p is described [6].
  • Many of these genes are involved in various cancers, including GASC1, shown previously to be amplified in ESCCs, and EPHB1 and PIK3C3 [7].

Biological context of PIK3C3

  • METHODS: The promoter region of PIK3C3 was analyzed for mutations by single-strand conformation polymorphism analysis and sequencing [2].
  • Here, cDNA cloning is used to show that the amino acid sequence of this protein, termed p150, is 29.6% identical and 53% similar to the yeast Vps15p protein, an established regulator of Vps34p [8].
  • However, an alternative role for Beclin 1 in modulating normal Vps34-dependent protein trafficking pathways has not been ruled out [9].
  • Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking [9].
  • We demonstrate that BEC-1 is necessary for the function of the class III PI3 kinase LET-512/Vps34, an essential protein required for autophagy, membrane trafficking, and endocytosis [10].

Anatomical context of PIK3C3

  • TbVps34, the Trypanosome Orthologue of Vps34, Is Required for Golgi Complex Segregation [11].
  • Overall, these findings indicate that hVps34 plays a major role in generating PtdIns(3)P for internal vesicle formation in multivesicular/late endosomes [1].
  • However, Rab5 does not appear to act by directly recruiting p150/hVps34 complexes from the cytosol to the endosomal membrane [12].

Associations of PIK3C3 with chemical compounds


Regulatory relationships of PIK3C3


Other interactions of PIK3C3

  • Unexpectedly, we found that a major pathway by which amino acids control mTOR signaling is distinct from that of insulin and that, instead of signaling through components of the insulin/class 1 PI3K pathway, amino acids mediate mTOR activation by signaling through class 3 PI3K, hVps34 [16].
  • Vps34p is a phosphatidylinositol 3-kinase that is part of a membrane-associated complex with the Vps15p protein kinase [14].
  • By contrast, the suppression of hVps34 expression did not block trafficking of cathepsin D between the TGN and late endosomes, or endocytic uptake of fluid-phase markers, or association of a PtdIns(3)P-binding protein, EEA1, with early endosomes [1].
  • LAMP1-positive vacuoles were depleted of PtdIns(3)P in the hVps34-knockdown cells, as judged by their inability to bind the PtdIns(3)P probe GFP-2xFYVE [1].
  • Role of Rab5 in the recruitment of hVps34/p150 to the early endosome [12].


  1. Gene silencing reveals a specific function of hVps34 phosphatidylinositol 3-kinase in late versus early endosomes. Johnson, E.E., Overmeyer, J.H., Gunning, W.T., Maltese, W.A. J. Cell. Sci. (2006) [Pubmed]
  2. Identification of PIK3C3 promoter variant associated with bipolar disorder and schizophrenia. Stopkova, P., Saito, T., Papolos, D.F., Vevera, J., Paclt, I., Zukov, I., Bersson, Y.B., Margolis, B.A., Strous, R.D., Lachman, H.M. Biol. Psychiatry (2004) [Pubmed]
  3. Phosphoinositide 3-kinases and membrane traffic. Shepherd, P.R., Reaves, B.J., Davidson, H.W. Trends Cell Biol. (1996) [Pubmed]
  4. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. Shin, H.W., Hayashi, M., Christoforidis, S., Lacas-Gervais, S., Hoepfner, S., Wenk, M.R., Modregger, J., Uttenweiler-Joseph, S., Wilm, M., Nystuen, A., Frankel, W.N., Solimena, M., De Camilli, P., Zerial, M. J. Cell Biol. (2005) [Pubmed]
  5. Wortmannin causes mistargeting of procathepsin D. evidence for the involvement of a phosphatidylinositol 3-kinase in vesicular transport to lysosomes. Davidson, H.W. J. Cell Biol. (1995) [Pubmed]
  6. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. Volinia, S., Dhand, R., Vanhaesebroeck, B., MacDougall, L.K., Stein, R., Zvelebil, M.J., Domin, J., Panaretou, C., Waterfield, M.D. EMBO J. (1995) [Pubmed]
  7. Genome-wide association study in esophageal cancer using GeneChip mapping 10K array. Hu, N., Wang, C., Hu, Y., Yang, H.H., Giffen, C., Tang, Z.Z., Han, X.Y., Goldstein, A.M., Emmert-Buck, M.R., Buetow, K.H., Taylor, P.R., Lee, M.P. Cancer Res. (2005) [Pubmed]
  8. Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex. Panaretou, C., Domin, J., Cockcroft, S., Waterfield, M.D. J. Biol. Chem. (1997) [Pubmed]
  9. Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. Zeng, X., Overmeyer, J.H., Maltese, W.A. J. Cell. Sci. (2006) [Pubmed]
  10. Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans. Takacs-Vellai, K., Vellai, T., Puoti, A., Passannante, M., Wicky, C., Streit, A., Kovacs, A.L., Müller, F. Curr. Biol. (2005) [Pubmed]
  11. TbVps34, the Trypanosome Orthologue of Vps34, Is Required for Golgi Complex Segregation. Hall, B.S., Gabernet-Castello, C., Voak, A., Goulding, D., Natesan, S.K., Field, M.C. J. Biol. Chem. (2006) [Pubmed]
  12. Role of Rab5 in the recruitment of hVps34/p150 to the early endosome. Murray, J.T., Panaretou, C., Stenmark, H., Miaczynska, M., Backer, J.M. Traffic (2002) [Pubmed]
  13. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. Byfield, M.P., Murray, J.T., Backer, J.M. J. Biol. Chem. (2005) [Pubmed]
  14. The C terminus of the Vps34p phosphoinositide 3-kinase is necessary and sufficient for the interaction with the Vps15p protein kinase. Budovskaya, Y.V., Hama, H., DeWald, D.B., Herman, P.K. J. Biol. Chem. (2002) [Pubmed]
  15. Nutrient sensing in the mTOR/S6K1 signalling pathway. Gulati, P., Thomas, G. Biochem. Soc. Trans. (2007) [Pubmed]
  16. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Nobukuni, T., Joaquin, M., Roccio, M., Dann, S.G., Kim, S.Y., Gulati, P., Byfield, M.P., Backer, J.M., Natt, F., Bos, J.L., Zwartkruis, F.J., Thomas, G. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
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