Hypoxia-inducible factor prolyl hydroxylase 1 (HIF-PH1) (HIF-PH1)

Hypoxia-inducible factor prolyl hydroxylase 1 (HIF-PH1), also known as PHD1 or EGLN2, is a member of the prolyl hydroxylase domain family that serves as a critical oxygen sensor within the cell (UniProt Q96KS0). Under normoxic conditions, HIF-PH1 catalyzes the site-specific hydroxylation of proline residues on the alpha subunit of hypoxia-inducible factor (HIF), a modification that facilitates its binding to the von Hippel-Lindau (VHL) protein and subsequent degradation by the proteasome (PubMed: 11595184). When oxygen levels drop or the enzyme is pharmacologically inhibited, HIF-alpha subunits accumulate and dimerize with HIF-beta, translocating to the nucleus to activate the transcription of genes involved in erythropoiesis, iron metabolism, and angiogenesis (PubMed: 21148455). This mechanism is the basis for a class of drugs known as HIF-PH inhibitors, such as Roxadustat and Daprodustat, which are used to treat anemia associated with chronic kidney disease by boosting endogenous erythropoietin production (FDA: Jesduvroq Label). Beyond its role in red blood cell production, HIF-PH1 is implicated in the regulation of cellular metabolism and the response to oxidative stress, making it a potential target in ischemia-reperfusion injury and oncology (PubMed: 27535443).

Other names

PHD1EGLN2Prolyl hydroxylase domain-containing protein 1HPH-3Egl nine homolog 2

Inhibition of prolyl hydroxylase activity, which prevents the degradation of HIF-alpha subunits, leading to increased expression of erythropoietin and improved iron utilization.