The domain within your query sequence starts at position 27 and ends at position 172; the E-value for the VHL domain shown below is 3e-76.



PFAM accession number:PF01847
Interpro abstract (IPR024053):

von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [ (PUBMED:17998064) (PUBMED:19671042) (PUBMED:19657325) (PUBMED:19414081) (PUBMED:19402056) (PUBMED:19261475) (PUBMED:19243301) (PUBMED:19216840) (PUBMED:10205047) (PUBMED:12050673) (PUBMED:12004076) (PUBMED:15611513) (PUBMED:18095884) (PUBMED:17932373) (PUBMED:17255293) (PUBMED:17245122) (PUBMED:18323857) (PUBMED:16728571) (PUBMED:16531988) (PUBMED:16869749) ].

Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller alpha-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [ (PUBMED:10205047) ].

This entry represents the beta domain of VHL.

This is a PFAM domain. For full annotation and more information, please see the PFAM entry VHL