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

VHL (P40337) - Overview - Molecular Target Synopsis


VHL, von Hippel-Lindau disease tumor suppressor
UniProt P40337

Also Known as VHL_HUMAN, VHL

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2. Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins. Interacts with CUL2; this interaction is dependent on the integrity of the trimeric VBC complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiquitination and degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal. Interacts with ADRB2; the interaction, in normoxia, is dependent on hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically decreased. Interacts with RNF139, USP33 and JADE1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via LIM domains). Interacts with EPAS1. Interacts with CARD9.

Inspect Structure
See all 3D Structures for VHL

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Sub-cellular localization

UniProt: VHL is active in the following subcellular-locations: cytoplasm, membrane, nucleus.
GO terms: VHL is active in the following subcellular-locations: cytosol, endoplasmic reticulum, membrane, mitochondrion, nucleoplasm, nucleus, VCB complex.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project VHL has gain in 4 cell-lines, loss in 2 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: MCF7, SK_OV_3, HL_60

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: BICR 31, RERF-GC-1B, SK-N-DZ

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: MCF-7, HeLa-S3, HSMM

(see details)

3D Structures

For VHL there are:
47 structures (160 chains) solved
36 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

VHL has been screened with 40 compounds (76 bioactivities), 5 compounds have bioactivities that show binding affinity of <= 500nM (5 bioactivities). (see details)