PROSITE documentation PDOC51546Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profiles
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 p110α, p110β or p110delta) or the p101 type (associated with the class IB p110 isoform p110γ). Common to all catalytic subunits are the N-terminal adaptor-binding domain (ABD) (see <PDOC51544>) 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 <PDOC00710>). Class II PI3Ks lack the ABD domain and are distinguished by a carboxy terminal C2 domain (see <PDOC00380>). Class III enzymes lack the ABD and RBD domains [1,2,3,4].
PI3K RBD is a small globular domain of about 100 residues in length with an α/β-sandwich topology (see <PDB:2RD0>). The PI3K RBD domain consists of a five-stranded mixed β-sheet flanked by two α-helices [1,2,3,4].
The profile we developed covers the entire PI3K RBD domain.
Last update:August 2011 / First entry.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | 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. |
| Title | Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. | |
| Source | Science 317:239-242(2007). | |
| PubMed ID | 17626883 | |
| DOI | 10.1126/science.1135394 |
| 2 | Authors | Huang C.-H. Mandelker D. Schmidt-Kittler O. Samuels Y. Velculescu V.E. Kinzler K.W. Vogelstein B. Gabelli S.B. Amzel L.M. |
| Title | The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. | |
| Source | Science 318:1744-1748(2007). | |
| PubMed ID | 18079394 | |
| DOI | 10.1126/science.1150799 |
| 3 | Authors | 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. |
| Title | The p110delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. | |
| Source | Nat. Chem. Biol. 6:244-244(2010). | |
| PubMed ID | 20154668 | |
| DOI | 10.1038/nchembio0310-244b |
| 4 | Authors | Walker E.H. Perisic O. Ried C. Stephens L. Williams R.L. |
| Title | Structural insights into phosphoinositide 3-kinase catalysis and signalling. | |
| Source | Nature 402:313-320(1999). | |
| PubMed ID | 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 prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)