The Enzyme Database

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EC 1.14.11.29     
Accepted name: hypoxia-inducible factor-proline dioxygenase
Reaction: hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
Other name(s): HIF hydroxylase
Systematic name: hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)
Comments: Contains iron, and requires ascorbate. Specifically hydroxylates a proline residue in HIF-α, the α 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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Kriegsheim Av, Hebestreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W. and Ratcliffe, P.J. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292 (2001) 468–472. [PMID: 11292861]
2.  Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J.M., Lane, W.S. and Kaelin , W.G., Jr. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292 (2001) 464–468. [PMID: 11292862]
3.  Bruick, R.K. and McKnight, S.L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294 (2001) 1337–1340. [PMID: 11598268]
4.  Epstein, A.C., Gleadle, J.M., McNeill, L.A., Hewitson, K.S., O'Rourke, J., Mole, D.R., Mukherji, M., Metzen, E., Wilson, M.I., Dhanda, A., Tian, Y.M., Masson, N., Hamilton, D.L., Jaakkola, P., Barstead, R., Hodgkin, J., Maxwell, P.H., Pugh, C.W., Schofield, C.J. and Ratcliffe, P.J. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107 (2001) 43–54. [PMID: 11595184]
5.  Oehme, F., Ellinghaus, P., Kolkhof, P., Smith, T.J., Ramakrishnan, S., Hutter, J., Schramm, M. and Flamme, I. Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors. Biochem. Biophys. Res. Commun. 296 (2002) 343–349. [PMID: 12163023]
6.  McNeill, L.A., Hewitson, K.S., Gleadle, J.M., Horsfall, L.E., Oldham, N.J., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J. and Schofield, C.J. The use of dioxygen by HIF prolyl hydroxylase (PHD1). Bioorg. Med. Chem. Lett. 12 (2002) 1547–1550. [PMID: 12039559]
[EC 1.14.11.29 created 2010]
 
 


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