Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

PIK3R4 (Q99570) - Overview - Molecular Target Synopsis


PIK3R4, Phosphoinositide 3-kinase regulatory subunit 4
Enzyme Classification
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.

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)