von Hippel-Lindau tumour suppressor protein (IPR002714)

Short name: VHL

Overlapping homologous superfamilies

Family relationships



VHL (von Hippel-Lindau disease tumor suppressor) is a 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 [PMID: 9122164]. Human VHL has been demonstrated to form a ternary complex with elonginB O44226 and elonginC O13292 proteins [PMID: 10205047]. This complex binds Cul2, which then is involved in regulation of vascular endothelial growth factor mRNA. VHL appears to act as the target recruitment subunit in the E3 ubiquitin ligase complex and recruit hydroxylated hypoxia-inducible factor (HIF) under normal oxygen conditions [PMID: 10944113]. VHL is also involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases [PMID: 12050673].

Like human VHL, Drosophila VHL complex containing Cul-2, Rbx1, Elongins B and C, exhibits E3 ubiquitin ligase activity [PMID: 11006129]. However, proteins in this entry also include Von Hippel-Lindau-like (VHLL) protein from human. It may has little or no E3 ubiquitin ligase activity as it lacks the alpha domain required for nucleating the multiprotein E3 ubiquitin ligase complex [PMID: 14757845].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.