von Hippel-Lindau disease tumor suppressor; pVHL; protein G7 (VHL)
Jump to navigation
Jump to search
Function
- role in ubiquitination & subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex
- seems to act as target recruitment subunit in the E3 ubiquitin ligase complex & recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions
- involved in transcriptional repression through interaction with HIF1A, HIF1AN & histone deacetylases
- protein modification; protein ubiquitination component of the VCB complex (VHL-elongin B, elongin C-CUL2 complex)
- interaction with CUL2 is dependent on integrity of the trimeric VBC complex
- interacts (via beta domain) with HIF1A (via NTAD domain); this interaction mediates degradation of HIF1A in normoxia &, in hypoxia, prevents ubiqitination & degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal
- interacts with RNF139 & UBP33
- interacts with PHF17
Structure
- the elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]
Compartment
Alternative initiation
named isoforms=3
Expression
- expressed in the adult & fetal brain & kidney
Pathology
- loss of VHL heterozygosity are a cause of pheochromocytoma
- defects in VHL are the cause of
- von Hippel-lindau disease
- erythrocytosis familial type 2
- renal cell carcinoma type 1
- some cases of sporadic cerebellar hemangioblastoma
- ~70% of mutations affect region involved in elongin binding
- VHL associated tumors show upregulation of vascular endothelial growth factor (VEGF) & wild type inhibits VEGF promoter activity
Notes
- VHL forms a complex (VCB complex) with elongin C & elongin B
- VCB also binds cul2 (cul2 - elongin C association), elongin & suppressor of cytokine signaling family proteins[4]
More general terms
Additional terms
Component of
References
- ↑ OMIM https://mirror.omim.org/entry/193300
- ↑ UniProt http://www.uniprot.org/uniprot/P40337.html
- ↑ Iliopoulos O et al. Tumour suppression by the human von Hippel-Lindau gene product. Nature Med 1:822-6 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7585187
- ↑ 4.0 4.1 Stebbins CE et al. Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science 284:455-61, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10205047
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7428
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/VHLID132.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=VHL
Database
- UniProt: http://www.uniprot.org/uniprot/P40337.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7428
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7428
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7428
- OMIM: https://mirror.omim.org/entry/144700
- OMIM: https://mirror.omim.org/entry/171300
- OMIM: https://mirror.omim.org/entry/193300
- OMIM: https://mirror.omim.org/entry/263400
- OMIM: https://mirror.omim.org/entry/608537