Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A.

Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes.

EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif

Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation.

Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EPAS1.

Interacts with CBFA2T3 and HIF1A

Expressed in heart, brain liver, skeletal muscle and kidney. Low levels were detected in the lung. Constitutively expressed during differentiation of C2C12 skeletal myocytes

The beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity