Egl nine homolog 3; hypoxia-inducible factor prolyl hydroxylase 3; HIF-PH3; HIF-prolyl hydroxylase 3; HPH-3; prolyl hydroxylase domain-containing protein 3; PHD3 (EGLN3)

Function

• catalyzes post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins
• hydroxylates HIF-1 alpha at 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)
• may play a role in cell growth regulation in muscle cells & in apoptosis in neuronal tissue
• promotes cell death through a caspase-dependent mechanism (putative)
• activated in cardiovascular cells & HelA cells following exposure to hypoxia
• interacts with MORG1 (putative)

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

contains 1 Fe2OG dioxygenase domain

Compartment

cytoplasm. nucleus

Expression

• widely expressed at low levels
• expressed at higher levels in heart (cardiac myocytes, aortic endothelial cells & coronary artery smooth muscle) & placenta

More general terms

• HIF-prolyl hydroxylase

Additional terms

• hypoxia inducible factor

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=112399
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:112399
• OMIM: https://mirror.omim.org/entry/606426
• UniProt: http://www.uniprot.org/uniprot/Q9H6Z9.html