Egl nine homolog 2; estrogen-induced tag 6; hypoxia-inducible factor prolyl hydroxylase 1; HIF-PH1; HIF-prolyl hydroxylase 1; HPH-1; prolyl hydroxylase domain-containing protein 1; PHD1 (EGLN2, EIT6)

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)
• may play a role in cell growth regulation
• isoform p40 & isoform p43 exhibit the same level of activity
• interacts with the E3 ubiquitin-protein ligase SIAH2, with isoform p40 having a higher propensity to bind than isoform p43; in vitro, the interaction targets both isoforms for proteasomal degradation

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

Alternative initiation

Named isoforms=2; p43; p40

Expression

• expressed abundantly in all tissues
• highest expression in testis
• expressed in hormone responsive tissues, including normal & malignant mammary, ovarian & prostate epithelium
• induced by estrogen
• isoform p43 induced & its protein stability enhanced by hypoxia
• isoform p40 repressed by hypoxia
• isoform p40 & isoform p43 induced by proteasomal inhibitor MG132 (at protein level)

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=112398
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:112398
• OMIM: https://mirror.omim.org/entry/606424
• UniProt: http://www.uniprot.org/uniprot/Q96KS0.html