{PDOC51547} {PS51547; C2_PI3K} {BEGIN} *************************************************************** * C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile * *************************************************************** Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that phosphorylate 4,5-bisphonate (PI(4,5) P2 or PIP2) at the 3-position of the inositol ring, and thus generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which, in turns, initiates a vast array of signaling events. PI3Ks can be grouped into three classes based on their domain organization. Class I PI3Ks are heterodimers consisting of a p110 catalytic subunit and a regulatory subunit of either the p85 type (associated with the class IA p110 isoforms p110alpha, p110beta or p110delta) or the p101 type (associated with the class IB p110 isoform p110gamma). Common to all catalytic subunits are the N-terminal adaptor-binding domain (ABD) (see ) that binds to p85, the Ras- binding domain (RBD), the putative membrane-binding domain (C2), the helical domain of unknown function, and the kinase catalytic domain (see ). Class II PI3Ks lack the ABD domain and are distinguished by a carboxy terminal C2 domain (see ). Class III enzymes lack the ABD and RBD domains [1,2,3,4]. The PI3K-type C2 domain is an eight-stranded antiparallel beta-sandwich consisting of two four-stranded beta-sheets (see ) [1,2,3,4]. The profile we developed covers the entire PI3K-type C2 domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2011 / First entry. [ 1] Miled N., Yan Y., Hon W.-C., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson H.J., Backer J.M., Williams R.L. "Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit." Science 317:239-242(2007). PubMed=17626883; DOI=10.1126/science.1135394 [ 2] Huang C.-H., Mandelker D., Schmidt-Kittler O., Samuels Y., Velculescu V.E., Kinzler K.W., Vogelstein B., Gabelli S.B., Amzel L.M. "The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations." Science 318:1744-1748(2007). PubMed=18079394; DOI=10.1126/science.1150799 [ 3] Berndt A., Miller S., Williams O., Le D.D., Houseman B.T., Pacold J.I., Gorrec F., Hon W.-C., Liu Y., Rommel C., Gaillard P., Rueckle T., Schwarz M.K., Shokat K.M., Shaw J.P., Williams R.L. "The p110delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors." Nat. Chem. Biol. 6:244-244(2010). PubMed=20154668; DOI=10.1038/nchembio0310-244b [ 4] Walker E.H., Perisic O., Ried C., Stephens L., Williams R.L. "Structural insights into phosphoinositide 3-kinase catalysis and signalling." Nature 402:313-320(1999). PubMed=10580505; DOI=10.1038/46319 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}