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PROSITE documentation PDOC00710 [for PROSITE entry PS00916] |
Phosphatidylinositol 3-kinase (PI3-kinase) (EC 2.7.1.137) [1] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The exact function of the three products of PI3-kinase - PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3) - is not yet known, although it is proposed that they function as second messengers in cell signalling. Currently, three forms of PI3-kinase are known:
Phosphatidylinositol 4-kinase (PI4-kinase) (EC 2.7.1.67) [4] is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate. Currently the following forms of PI4-kinases are known:
The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain of protein kinases [2]. The PI3K/PI4K catalytic domain is divided into an N-lobe and a C-lobe (see <PDB:4HNE>). The N-lobe contains a five-stranded $antiparallel β-sheet core flanked by a helical hairpin on one side and a helix on the other. The C-lobe contains helices, which form a helical bundle together with the N-lobe helix. The helical bundle is flanked by three β-strands and a helix. Three loops are related to kinase activity, the glycine-rich G-loop, the catalytic loop and the activation loop. The G-loop has been reported to bind to the phosphate group of nucleotides [5].
Four additional proteins belong to this family:
We developed two signature patterns from the best conserved parts of the C-terminal domain. A profile was also developed that spans the complete domain.
Last update:October 2021 / Profile and text revised.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Hiles I.D. Otsu M. Volinia S. Fry M.J. Gout I. Dhand R. Panayotou G. Ruiz-Larrea F. Thompson A. Totty N.F. |
Title | Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. | |
Source | Cell 70:419-429(1992). | |
PubMed ID | 1322797 |
2 | Authors | Kunz J. Henriquez R. Schneider U. Deuter-Reinhard M. Movva N.R. Hall M.N. |
Title | Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. | |
Source | Cell 73:585-596(1993). | |
PubMed ID | 8387896 |
3 | Authors | Schu P.V. Takegawa K. Fry M.J. Stack J.H. Waterfield M.D. Emr S.D. |
Title | Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. | |
Source | Science 260:88-91(1993). | |
PubMed ID | 8385367 |
4 | Authors | Garcia-Bustos J.F. Marini F. Stevenson I. Frei C. Hall M.N. |
Title | PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus. | |
Source | EMBO. J. 13:2352-2361(1994). | |
PubMed ID | 8194527 |
5 | Authors | Zhou Q. Li J. Yu H. Zhai Y. Gao Z. Liu Y. Pang X. Zhang L. Schulten K. Sun F. Chen C. |
Title | Molecular insights into the membrane-associated phosphatidylinositol 4-kinase IIalpha. | |
Source | Nat. Commun. 5:3552-3552(2014). | |
PubMed ID | 24675427 | |
DOI | 10.1038/ncomms4552 |
6 | Authors | Brown E.J. Albers M.W. Shin T.B. Ichikawa K. Keith C.T. Lane W.S. Schreiber S.L. |
Title | A mammalian protein targeted by G1-arresting rapamycin-receptor complex. | |
Source | Nature 369:756-758(1994). | |
PubMed ID | 8008069 | |
DOI | 10.1038/369756a0 |
7 | Authors | Kato R. Ogawa H. |
Title | An essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae. | |
Source | Nucleic Acids Res. 22:3104-3112(1994). | |
PubMed ID | 8065923 |