KEGG   ENZYME: 1.14.11.30Help
Entry
EC 1.14.11.30               Enzyme                                 

Name
hypoxia-inducible factor-asparagine dioxygenase;
HIF hydroxylase
Class
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
Sysname
hypoxia-inducible factor-L-asparagine, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)
Reaction(IUBMB)
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2
Substrate
hypoxia-inducible factor-L-asparagine;
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007]
Product
hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine;
succinate [CPD:C00042];
CO2 [CPD:C00011]
Comment
Contains iron, and requires ascorbate. Catalyses hydroxylation of an asparagine in the C-terminal transcriptional activation domain of HIF-alpha, the alpha 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.
Orthology
K18055  
hypoxia-inducible factor 1-alpha inhibitor (HIF hydroxylase)
Genes
HSA: 
55662(HIF1AN)
PTR: 
466183(HIF1AN)
PPS: 
100969925(HIF1AN)
GGO: 
101140559(HIF1AN)
PON: 
100450996(HIF1AN)
MCC: 
710425(HIF1AN)
MCF: 
102123484(HIF1AN)
MMU: 
319594(Hif1an)
RNO: 
309434(Hif1an)
CGE: 
HGL: 
101715790(Hif1an)
TUP: 
102471470(HIF1AN)
CFA: 
609221(HIF1AN)
AML: 
100484876(HIF1AN)
FCA: 
101091901(HIF1AN)
BTA: 
520864(HIF1AN)
BOM: 
102285023(HIF1AN)
PHD: 
102341833(HIF1AN)
CHX: 
102182662(HIF1AN)
SSC: 
CFR: 
102504253(HIF1AN)
ECB: 
100070337(HIF1AN)
MYB: 
102258997(HIF1AN)
MDO: 
100010508(HIF1AN)
SHR: 
100932046(HIF1AN)
OAA: 
GGA: 
428952(HIF1AN)
MGP: 
100547017(HIF1AN)
TGU: 
100224185(HIF1AN)
FAB: 
101815471(HIF1AN)
PHI: 
102110633(HIF1AN)
APLA: 
101796702(HIF1AN)
FPG: 
101910571(HIF1AN)
FCH: 
102050862(HIF1AN)
CLV: 
102094216(HIF1AN)
ASN: 
102372847(HIF1AN)
PSS: 
102461331(HIF1AN)
ACS: 
XLA: 
432095(hif1an)
XTR: 
394511(hif1an)
DRE: 
373126(hif1an)
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
102346962(HIF1AN)
BFO: 
CIN: 
TCA: 
664369(Hif1an)
API: 
PHU: 
ISC: 
NVE: 
AQU: 
EHX: 
GTT: 
HAO: 
GLP: 
 » show all
Taxonomy
Reference
1  [PMID:11641274]
  Authors
Mahon PC, Hirota K, Semenza GL
  Title
FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity.
  Journal
Genes. Dev. 15 (2001) 2675-86.
  Organism
Homo sapiens [GN:hsa]
  Sequence
[hsa:55662]
Reference
2  [PMID:12042299]
  Authors
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
  Title
Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family.
  Journal
J. Biol. Chem. 277 (2002) 26351-5.
  Organism
Homo sapiens [GN:hsa]
  Sequence
[hsa:55662]
Reference
3  [PMID:12432100]
  Authors
Dann CE 3rd, Bruick RK, Deisenhofer J
  Title
Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 15351-6.
  Organism
Homo sapiens [GN:hsa]
  Sequence
[hsa:55662]
Reference
4  [PMID:11823643]
  Authors
Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML
  Title
Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.
  Journal
Science. 295 (2002) 858-61.
  Organism
Homo sapiens [GN:hsa]
  Sequence
[hsa:55662]
Reference
5  [PMID:14701857]
  Authors
Koivunen P, Hirsila M, Gunzler V, Kivirikko KI, Myllyharju J
  Title
Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases.
  Journal
J. Biol. Chem. 279 (2004) 9899-904.
  Organism
Homo sapiens [GN:hsa]
  Sequence
[hsa:55662]
Reference
6  [PMID:12446723]
  Authors
Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ
  Title
Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.
  Journal
J. Biol. Chem. 278 (2003) 1802-6.
  Organism
Homo sapiens [GN:hsa]
  Sequence
[hsa:55662]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

DBGET integrated database retrieval system