InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Pik3cb

Summary

InnateDB Protein

IDBP-192639.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Pik3cb

Protein Name

phosphatidylinositol 3-kinase, catalytic, beta polypeptide

Synonyms

1110001J02Rik; AI447572; p110beta;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000035037

InnateDB Gene

IDBG-192637 (Pik3cb)

Protein Structure

UniProt Annotation

Function

Phosphoinositide-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. {ECO:0000269PubMed:18544649, ECO:0000269PubMed:18594509, ECO:0000269PubMed:19515725, ECO:0000269PubMed:19940148, ECO:0000269PubMed:20065293, ECO:0000269PubMed:21059846}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Note=Interaction with PIK3R2 is required for nuclear localization and export.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 21 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	21 [view]
Protein-Protein	20 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016303	1-phosphatidylinositol-3-kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0035005	1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0043560	insulin receptor substrate binding
GO:0046934	phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process

GO:0001952	regulation of cell-matrix adhesion
GO:0006874	cellular calcium ion homeostasis
GO:0006897	endocytosis
GO:0006914	autophagy
GO:0007156	homophilic cell adhesion
GO:0030168	platelet activation
GO:0036092	phosphatidylinositol-3-phosphate biosynthetic process
GO:0040016	embryonic cleavage
GO:0046854	phosphatidylinositol phosphorylation
GO:0048015	phosphatidylinositol-mediated signaling

Cellular Component

GO:0005634	nucleus
GO:0005886	plasma membrane
GO:0005942	phosphatidylinositol 3-kinase complex

Protein Structure and Domains

PDB ID

MGI:1922019

InterPro

IPR000008 C2 domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR003113 Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain
IPR011009 Protein kinase-like domain
IPR016024 Armadillo-type fold
IPR029071 Ubiquitin-related domain

PFAM

PF00168
PF00794
PF00454
PF00613
PF00792
PF02192

PRINTS

PR00360

PIRSF

SMART

SM00239
SM00144
SM00146
SM00145
SM00142
SM00143

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt