LMPD Database

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LMP012824

UniProt Annotations

Entry Information
Gene Namephosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Protein EntryPK3CB_RAT
UniProt IDQ9Z1L0
SpeciesRat
Comments
Comment typeDescription
Catalytic ActivityATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate.
DomainThe inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N- terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival (By similarity)
FunctionPhosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors (By similarity)
PathwayPhospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
SimilarityBelongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-ProRule:PRU00877, ECO:0000255|PROSITE- ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}.
SimilarityContains 1 C2 PI3K-type domain. {ECO:0000255|PROSITE- ProRule:PRU00880}.
SimilarityContains 1 PI3K-ABD domain. {ECO:0000255|PROSITE- ProRule:PRU00877}.
SimilarityContains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE- ProRule:PRU00269}.
SimilarityContains 1 PI3K-RBD domain. {ECO:0000255|PROSITE- ProRule:PRU00879}.
SimilarityContains 1 PIK helical domain. {ECO:0000255|PROSITE- ProRule:PRU00878}.
Subcellular LocationCytoplasm . Nucleus . Note=Interaction with PIK3R2 is required for nuclear localization and export.
SubunitHeterodimer of a catalytic subunit PIK3CB and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required for nuclear localization and nuclear export (By similarity). Part of a complex with PIK3R1 and PTEN (By similarity). Binding to PTEN may antagonize the lipid kinase activity under normal growth conditions (By similarity). Part of a complex involved in autophagosome formation composed of PIK3C3 and PIK3R4 (By similarity). Interacts with BECN1, ATG14 and RAB5A (By similarity)