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. According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Cellular Component: cytoplasm; cytosol; glutamatergic synapse; nucleus; postsynaptic density
Molecular Function: enzyme binding; ferrous iron binding; L-ascorbic acid binding; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors; peptidyl-proline 4-dioxygenase activity; peptidyl-proline dioxygenase activity; protein binding
Biological Process: cardiac muscle tissue morphogenesis; cellular iron ion homeostasis; heart trabecula formation; labyrinthine layer development; negative regulation of cyclic-nucleotide phosphodiesterase activity; negative regulation of DNA-binding transcription factor activity; oxidation-reduction process; oxygen homeostasis; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; positive regulation of transcription by RNA polymerase II; regulation of angiogenesis; regulation of neuron death; regulation of postsynapse organization; regulation of protein catabolic process at postsynapse, modulating synaptic transmission; regulation of transcription from RNA polymerase II promoter in response to hypoxia; response to hypoxia; response to nitric oxide; ventricular septum morphogenesis