Recombinant Human Egl nine homolog 1 (EGLN1), partial

Function

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

Subcellular Location

Cytoplasm; Nucleus

Disease Association

Erythrocytosis, familial, 3 (ECYT3) : An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

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

Subunit

(Microbial infection) Interacts with vaccinia virus protein C16; this interaction inhibits PHD2-dependent hydroxylation of HIF-1alpha

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• Hirsila M. et al. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. — J. Biol. Chem. (2003)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Yu W.-Q. et al. Human acute promyelocytic leukemia cell line NB4's apoptosis related genes. (JUN-)
• Semenza G.L. et al. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. — Cell (2001)
• Epstein A.C.R. et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. — Cell (2001)