MetaCyc Reaction:

Superclasses: Reactions Classified By Conversion TypeSimple ReactionsChemical ReactionsProtein-Modification Reactions
Reactions Classified By SubstrateMacromolecule ReactionsProtein-ReactionsProtein-Modification Reactions

EC Number:

Enzymes and Genes:

Homo sapiens: hypoxia-inducible factor-asparagine dioxygenaseInferred from experiment: HIF1AN

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

Mass balance status: Balance undetermined; a substrate lacks a chemical formula

Enzyme Commission Primary Name: hypoxia-inducible factor-asparagine dioxygenase

Enzyme Commission Synonyms: HIF hydroxylase

Taxonomic Range: Metazoa

Enzyme Commission Summary:
Contains iron, and requires ascorbate. Catalyses hydroxylation of an asparagine in the C-terminal transcriptional activation domain of HIF-α, the α subunit of the transcriptional regulator HIF (hypoxia-inducible factor), which reduces its interaction with the transcriptional coactivator protein p300. The requirement of oxygen for the hydroxylation reaction enables animals to respond to hypoxia.

Citations: [Dann02, Lando02, Koivunen04, Mahon01, Hewitson02, Elkins03]

Gene-Reaction Schematic

Gene-Reaction Schematic

Relationship Links: BRENDA:EC:, ENZYME:EC:, IUBMB-ExplorEnz:EC:

Created 15-Mar-2010 by Caspi R, SRI International


Dann02: Dann CE, Bruick RK, Deisenhofer J (2002). "Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway." Proc Natl Acad Sci U S A 99(24);15351-6. PMID: 12432100

Elkins03: Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ (2003). "Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha." J Biol Chem 278(3);1802-6. PMID: 12446723

Hewitson02: Hewitson KS, McNeill LA, Riordan MV, Tian YM, Bullock AN, Welford RW, Elkins JM, Oldham NJ, Bhattacharya S, Gleadle JM, Ratcliffe PJ, Pugh CW, Schofield CJ (2002). "Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family." J Biol Chem 277(29);26351-5. PMID: 12042299

Koivunen04: Koivunen P, Hirsila M, Gunzler V, Kivirikko KI, Myllyharju J (2004). "Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases." J Biol Chem 279(11);9899-904. PMID: 14701857

Lando02: Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002). "Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch." Science 295(5556);858-61. PMID: 11823643

Mahon01: Mahon PC, Hirota K, Semenza GL (2001). "FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity." Genes Dev 15(20);2675-86. PMID: 11641274

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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