PHD1 (Egln2), PHD­2 (Egln1), and PHD3 (Egln3) are members of the Egln family of proline hydroxylases. They function as oxygen sensors that catalyze the hydroxylation of HIF on prolines 564 and 402, initiating the first step of HIF degradation through the VHL/ubiquitin pathway. PHD1 is highly expressed in a wide array of tissues whereas PHD2 and PHD3 are expressed mainly in heart and skeletal muscle. The mRNA levels of PHD are upregulated by HIF through the hypoxia response element under low oxygen conditions. These three enzymes also exhibit different peptide specificity target proteins, PHD1 and PHD2 can hydroxylate both proline 402 and proline 564, but PHD3 can only hydroxylate proline 564. In addition to HIF, PHD enzymes have also has been shown to catalyze the hydroxylation of RNA polymerase subunits and myogenin.