VHL complex, active

Background Information:

VHL is a tumor suppressor protein that serves as the substrate recognition subunit of a VHL multiprotein E3 ubiquitin ligase complex (Cul2–Elongin B-Elongin C–Rbx1–VHL). Under normal oxygen conditions, VHL binds hydroxylated forms of the transcription factor HIF1-alpha, leading to its ubiquitination and proteasomal degradation. When VHL is inactivated (via mutation or deletion), HIF1-alpha accumulates, drives expression of genes such as VEGF, PDGF, and others that promote angiogenesis, proliferation, and metabolic adaptation. VHL germline mutations cause Von Hippel–Lindau disease, a hereditary cancer syndrome with tumors in kidney, CNS hemangioblastoma, pheochromocytoma, pancreatic cysts, and other lesions. VHL has become one of the most widely used “hook” proteins in targeted protein degradation (TPD) strategies (eg. PROTACs) because small molecules that bind VHL can recruit disease-relevant target proteins to the VHL E3 machinery for ubiquitination and degradation.

Target Class:

Ubiquitination-related

Family:

VHL

Sub Family:

E3 Ligase

Protein Name:

VHL

Protein Aliases:

Protein G7; pVHL (VHL)

Accession Number:

NM_000551.3 (VHL); NM_007108.2 (Elongin B); NM_005648.2 (Elongin C); NM_003591.3 (Cul2); NM_014248.

UniProt Number:

P40337 (VHL)

Gene Name:

VHL

Gene ID:

7428 (VHL)

Gene Aliases:

RCA1; VHL1; pVHL; HRCA1 (VHL)

Target Species:

Human