EGLN2 (EGL/EGg LayingNine #2; also known as PHD1 and HPH3) is a 43kD member of the EglN family of proteins. It is ubiquitously expressed and found principally in the nucleus. EGLN2 hydroxylates proline on HIF1 a. HIF1 is an a/b heterodimeric transcriptional activa that up regulates genes involved in mitigating the effects of hypoxia. Normally, and in the presence of abundant oxygen, the HIF 1 a chain is hydroxylated by PHD family members, which results in its ubiquitylation and degradation. Under low oxygen tension, EGLN2 activity is decreased, the HIF1 a subunit is retained, and HIF1 activates genes. Human EGLN2 is 407aa in length. It contains one iron 2oxoglutarate (Fe2OG) dioxygenase domain (aa278-376) plus an ironbinding (His297 His358), and a 2,oxoglutaratebinding (Arg367) site. There is one alternative start site at Met34 that generates a 40kD isoform. In addition, there is another potential splice form that shows a 16aa substitution for aa1281 fulllength human EGLN2 shares 91% aa sequence identity with mouse EGLN2.