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

PIK3R4 (Q99570) - Overview - Molecular Target Synopsis

Protein


PIK3R4, Phosphoinositide 3-kinase regulatory subunit 4
Enzyme Classification 2.7.11.1
UniProt Q99570

Also Known as PI3R4_HUMAN, PIK3R4, VPS15

Regulatory subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123). Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG (PubMed:8999962, PubMed:19270696, PubMed:23878393, PubMed:25490155). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (PubMed:25490155). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1, AMBRA1 and NRBF2 (PubMed:19270696, PubMed:20643123, PubMed:24785657). PI3KC3-C1 probably associates with PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3C3/VPS34 (PubMed:14617358). Interacts with NRBF2 (PubMed:24785657).

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PIK3R4 is active in the following subcellular-locations: autophagosome, cytoplasmic vesicle, late endosome, membrane.
GO terms: PIK3R4 is active in the following subcellular-locations: autophagosome, axoneme, cytosol, intracellular membrane-bounded organelle, late endosome, membrane, microtubule cytoskeleton, nucleus-vacuole junction, phagocytic vesicle membrane, phosphatidylinositol 3-kinase complex, phosphatidylinositol 3-kinase complex, phosphatidylinositol 3-kinase complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PIK3R4 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, UACC_62, MDA_MB_435

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NIH:OVCAR-3, HT-1080, COLO 794

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, HSMM, HMEC

(see details)

RNA Interference


PIK3R4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SCC47, DU4475. (see details)


Screening and Chemistry


PIK3R4 has been screened with 1 compounds (1 bioactivities). (see details)