|Superclasses:||Reactions Classified By Conversion Type → Simple Reactions → Chemical Reactions → Protein-Modification Reactions|
|Reactions Classified By Substrate → Macromolecule Reactions → Protein-Reactions → Protein-Modification Reactions|
EC Number: 18.104.22.168
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
Mass balance status: Undetermined; a substrate lacks a chemical formula
Enzyme Commission Primary Name: hypoxia-inducible factor-asparagine dioxygenase
Enzyme Commission Synonyms: HIF hydroxylase
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.
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
Elkins03a: 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
Hewitson02a: 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
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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