{PDOC51546}
{PS51546; PI3K_RBD}
{BEGIN}
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* Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profiles *
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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  <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
alpha/beta-sandwich topology (see <PDB:2RD0>). The PI3K RBD domain consists of
a five-stranded mixed beta-sheet flanked by two alpha-helices [1,2,3,4].

The profile we developed covers the entire PI3K RBD 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

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