PROSITE documentation PDOC51547 [for PROSITE entry PS51547]

Phosphatidylinositol 3-kinase C2 (PI3K C2) domain profile




Description

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].

The PI3K C2 domain is an eight-stranded antiparallel β-sandwich consisting of two four-stranded β-sheets (see <PDB:1E8X>) [1,2,3,4].

The profile we developed covers the entire PI3K C2 domain.

Last update:

August 2011 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

PI3K_C2, PS51547; Phosphatidylinositol 3-kinase C2 (PI3K C2) domain profile  (MATRIX)


References

1AuthorsMiled N., Yan Y., Hon W.-C., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson H.J., Backer J.M., Williams R.L.
TitleMechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit.
SourceScience 317:239-242(2007).
PubMed ID17626883
DOI10.1126/science.1135394

2AuthorsHuang C.-H., Mandelker D., Schmidt-Kittler O., Samuels Y., Velculescu V.E., Kinzler K.W., Vogelstein B., Gabelli S.B., Amzel L.M.
TitleThe structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations.
SourceScience 318:1744-1748(2007).
PubMed ID18079394
DOI10.1126/science.1150799

3AuthorsBerndt 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.
TitleThe p110delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.
SourceNat. Chem. Biol. 6:244-244(2010).
PubMed ID20154668
DOI10.1038/nchembio0310-244b

4AuthorsWalker E.H., Perisic O., Ried C., Stephens L., Williams R.L.
TitleStructural insights into phosphoinositide 3-kinase catalysis and signalling.
SourceNature 402:313-320(1999).
PubMed ID10580505
DOI10.1038/46319



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