Egl nine homolog 1; hypoxia-inducible factor prolyl hydroxylase 2; HIF-PH2; HIF-prolyl hydroxylase 2; HPH-2; prolyl hydroxylase domain-containing protein 2; PHD2; SM-20 (EGLN1, C1orf12, PNAS-118, PNAS-137)

Function

• catalyzes post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins
• hydroxylates HIF-1 alpha at Pro-402 & Pro-564, & HIF-2 alpha
• functions as a cellular oxygen sensor &, under normoxic conditions, targets HIF through the hydroxylation for proteasomal degradation via the VCB complex (von Hippel-Lindau ubiquitination complex)
• following exposure to hypoxia
  • activated in HeLa cells
  • not activated in cardiovascular cells
• seems to be inhibited by ING4

HIF alpha chain L-proline + 2-oxoglutarate + O2 = HIF alpha chain trans-4-hydroxy-L-proline + succinate + CO2

Cofactor:

• binds 1 Fe+2 ion per subunit
• ascorbate

Structure

• monomer
• contains 1 Fe2OG dioxygenase domain
• contains 1 MYND-type Zn+2 finger

Alternative splicing

named isoforms=2

Expression

• widely expressed
• expressed in brain, skeletal muscle & heart, pancreas, kidney, adrenal, lung & liver
• in brain expressed in dopaminergic neurons of adult & fetal substantia nigra
• expressed in cardiac myocytes, aortic endothelial cells & coronary artery smooth muscle

Pathology

• defects in EGLN1 are the cause of erythrocytosis familial type 3

More general terms

• HIF-prolyl hydroxylase
• zinc finger protein

Additional terms

• hypoxia inducible factor

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=54583
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:54583
• OMIM: https://mirror.omim.org/entry/606425
• OMIM: https://mirror.omim.org/entry/609820
• UniProt: http://www.uniprot.org/uniprot/Q9GZT9.html