1.14.11.29 2-oxoglutarate oxygenases C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

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Overview

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The hypoxia inducible factor (HIF) is a transcriptional complex that is involved in oxygen homeostasis [5]. At normal oxygen levels, the alpha subunit of HIF (HIF-1α) is targeted for degradation by prolyl hydroxylation by the PHD proteins 1-3 (HIF-PHs) whch are 2-oxoglutarate (2OG) oxygenases responsible for the post-translational modification of a specific proline in each of the oxygen-dependent degradation (ODD) domains of HIF-1α. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex [4]. Under hypoxic conditions, the hydroxylation reaction is blunted which results in decreased HIF degradation. The surviving HIFs are then available to translocate to the nucleus where they heterodimerize with HIF-1β, effecting increased expression of hypoxia-inducible genes.
HIF-PH enzymes are being investigated as pharmacological targets as their inhibition mimics the hypoxic state and switches on transcription of genes associated with processes such as erythropoiesis and vasculogenesis [3]. Small molecule HIF-PH inhibitors are in clinical trial as novel therapies for the amelioration of anemia associated with chronic kidney disease [1].

Enzymes

PHD1 (egl-9 family hypoxia inducible factor 2) C Show summary » More detailed page

PHD2 (egl-9 family hypoxia inducible factor 1) C Show summary » More detailed page

PHD3 (egl-9 family hypoxia inducible factor 3) C Show summary » More detailed page

References

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How to cite this family page

Database page citation:

1.14.11.29 2-oxoglutarate oxygenases. Accessed on 14/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=900.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Enzymes. Br J Pharmacol. 174 Suppl 1: S272-S359.