Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PIK3CA (P42336) - Overview - Molecular Target Synopsis

Protein


PIK3CA, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Enzyme Classification 2.7.1.153
UniProt P42336

Also Known as PK3CA_HUMAN, PIK3CA

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. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:26593112). Interacts with IRS1 in nuclear extracts (By similarity). Interacts with RUFY3 (By similarity). Interacts with RASD2 (By similarity). Interacts with APPL1. Interacts with HRAS and KRAS (By similarity). Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467).

6OAC
PQR530 [(S)-4-(DIFLUOROMETHYL)-5-(4-(3-METHYLMORPHOLINO)-6-MORPHOLINO- 1,3,5-TRIAZIN-2-YL)PYRIDIN-2-AMINE] BOUND TO THE PI3KA CATALYTIC SUBUNIT P110ALPHA
RCSB/PDB
Inspect Structure
See all 3D Structures for PIK3CA

Isoforms / Transcripts (Protein Coding)


Drugs


PIK3CA is targeted by Approved Drug BYL-719. (see details)
BYL-719

Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project PIK3CA has gain in 19 cell-lines, loss in 1 cell-lines and no signal in 985 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_435, MDA_N, T47D

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KYSE-70, WSU-FSCCL, Caov-3

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, AG445, HSMM

(see details)

RNA Interference


PIK3CA was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OVTOKO, KOC7C. (see details)

3D Structures


For PIK3CA there are:
47 structures (48 chains) solved
36 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

PIK3CA is solved in complex with the approved drug(s):

URF/FLUOROURACIL (5SXC_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PIK3CA has been screened with 7910 compounds (10362 bioactivities), 4015 compounds have bioactivities that show binding affinity of <= 500nM (4755 bioactivities). (see details)