EC Number |
Natural Substrates |
---|
1.14.11.29 | hypoxia-inducible factor 1 alpha-L-proline + 2-oxoglutarate + O2 |
- |
1.14.11.29 | hypoxia-inducible factor 1alpha-L-proline + 2-oxoglutarate + O2 |
- |
1.14.11.29 | hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2 |
- |
1.14.11.29 | hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 |
- |
1.14.11.29 | hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 |
HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). Human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. This protein modifiation may play a key role in mammalian oxygen sensing |
1.14.11.29 | more |
HIF prolyl-4-hydroxylase 2 substrate binding analysis using isolated sequences of the C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A, and the N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y, overview |
1.14.11.29 | hypoxia-inducible factor-proline + 2-oxoglutarate + O2 |
HIF-1alpha |
1.14.11.29 | hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 |
HIF1alpha is a better substrate than HIF2alpha for PHD2 |
1.14.11.29 | hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 |
hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor |
1.14.11.29 | hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 |
hypoxia-inducible factor 1alpha is hydroxylated at Pro402 and Pro564 |