**************************************************** * Phosphatidylinositol 3- and 4-kinases signatures * **************************************************** 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: - The mammalian enzyme which is a heterodimer of a 110 Kd catalytic chain (p110) and an 85 Kd subunit (p85) which allows it to bind to activated tyrosine protein kinases. - Yeast TOR1/DRR1 and TOR2/DRR2 [2], PI3-kinases required for cell cycle activation. Both are proteins of about 280 Kd. - Yeast VPS34 [3], a PI3-kinase involved in vacuolar sorting and segregation. VPS34 is a protein of about 100 Kd. Phosphatidylinositol 4-kinase (PI4-kinase) (EC 2.7.1.-) [4] is an enzyme that acts on phosphatidylinositol (PI) in the first commited step in the production of the second messenger inositol-1,4,5,-trisphosphate. Currently a single form of PI4-kinase is known: - Yeast PIK1, a nuclear protein of 120 Kd. 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]. We developed two signature patterns from the best conserved parts of this domain. -Consensus pattern: [LIVMFA]-K-x(2)-[DE](2)-[LIVM]-R-Q-[DE]-x(3)-[LIVMFY]-Q -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in SWISS-PROT: NONE. -Consensus pattern: S-x-A-x(3)-[LIVM]-x(2)-[FY]-[LIVM](2)-x-[LIVM]-x-D-R-H- x(2)-N -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in SWISS-PROT: NONE. -Last update: June 1994 / Patterns and text revised. [ 1] Hiles I.D., Otsu M., Volinia S., Fry M.J., Gout I., Dhand R., Panayotou G., Ruiz-Larrea F., Thompson A., Totty N.F., Hsuan J.J., Courtneidge S.A., Parker P.J., Waterfield M.D. Cell 70:419-429(1992). [ 2] Kunz J., Henriquez R., Schneider U., Deuter-Reinhard M., Movva N., Hall M.N. Cell 73:585-596(1993). [ 3] Schu P.V., Takegawa K., Fry M.J., Stack J.H., Waterfield M.D., Emr S.D. Science 260:88-91(1993). [ 4] Garcia-Bustos J.F., Marini F., Stevenson I., Frei C., Hall M.N. EMBO J. 13:2352-2361(1994).