Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
BRITE hierarchy

hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2

hypoxia-inducible factor-L-proline;
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007]

Contains iron, and requires ascorbate. Specifically hydroxylates a proline residue in HIF-alpha, the alpha subunit of the transcriptional regulator HIF (hypoxia-inducible factor), which targets HIF for proteasomal destruction. The requirement of oxygen for the hydroxylation reaction enables animals to respond to hypoxia.

EC 1.14.11.29 created 2010

1  [PMID:11292861]

Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim Av, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ

Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.

Science 292:468-72 (2001)
DOI:10.1126/science.1059796

[hsa:112398]

2  [PMID:11292862]

Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr

HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

Science 292:464-8 (2001)
DOI:10.1126/science.1059817

3  [PMID:11598268]

Bruick RK, McKnight SL

A conserved family of prolyl-4-hydroxylases that modify HIF.

Science 294:1337-40 (2001)
DOI:10.1126/science.1066373

[hsa:54583 112398 112399]

4  [PMID:11595184]

Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ

C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.

Cell 107:43-54 (2001)
DOI:10.1016/S0092-8674(01)00507-4

[hsa:54583 112398 112399]

5  [PMID:12163023]

Oehme F, Ellinghaus P, Kolkhof P, Smith TJ, Ramakrishnan S, Hutter J, Schramm M, Flamme I

Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors.

Biochem Biophys Res Commun 296:343-9 (2002)
DOI:10.1016/S0006-291X(02)00862-8

[hsa:54583 112398 112399]

6  [PMID:12039559]

McNeill LA, Hewitson KS, Gleadle JM, Horsfall LE, Oldham NJ, Maxwell PH, Pugh CW, Ratcliffe PJ, Schofield CJ

The use of dioxygen by HIF prolyl hydroxylase (PHD1).

Bioorg Med Chem Lett 12:1547-50 (2002)
DOI:10.1016/S0960-894X(02)00219-6

[hsa:112398]