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Entry
EC 1.14.11.29               Enzyme                                 

Name
hypoxia-inducible factor-proline 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-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)
Reaction(IUBMB)
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
Substrate
hypoxia-inducible factor-L-proline;
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007]
Product
hypoxia-inducible factor-trans-4-hydroxy-L-proline;
succinate [CPD:C00042];
CO2 [CPD:C00011]
Comment
Contains iron, and requires ascorbate. Specifically hydroxylates a proline residue in HIF-alpha, the alpha 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.
History
EC 1.14.11.29 created 2010
Orthology
K09592  
hypoxia-inducible factor prolyl hydroxylase
Genes
HSA: 
112398(EGLN2) 112399(EGLN3) 54583(EGLN1)
PTR: 
452850(EGLN3) 456049(EGLN2) 469708(EGLN1)
PPS: 
100971263(EGLN1) 100984867(EGLN2) 100990967(EGLN3)
GGO: 
101145572(EGLN2) 101147171(EGLN1) 101150306(EGLN3)
PON: 
100172704(EGLN2) 100451138(EGLN3) 100454843(EGLN1)
MCC: 
703083(EGLN2) 713410(EGLN1) 717342(EGLN3)
MCF: 
MMU: 
112405(Egln1) 112406(Egln2) 112407(Egln3)
RNO: 
308457(Egln2) 308913(Egln1) 54702(Egln3)
CGE: 
HGL: 
TUP: 
102482051(EGLN1) 102483132(EGLN2) 102502105(EGLN3)
CFA: 
480286(EGLN3) 484495(EGLN2) 488971(EGLN1)
AML: 
FCA: 
101082320(EGLN3) 101089964(EGLN1) 101090063(EGLN2)
PTG: 
102951182(EGLN3) 102957902(EGLN1) 102958475(EGLN2)
BTA: 
534075(EGLN1) 535578(EGLN3)
BOM: 
102280498(EGLN3) 102280646(EGLN2) 102287116(EGLN1)
PHD: 
102317356(EGLN2) 102334028(EGLN1) 102335283(EGLN3)
CHX: 
102179524(EGLN3) 102189459(EGLN1) 102191264(EGLN2)
SSC: 
100152368(EGLN3) 100153461(EGLN1) 100523673(EGLN2)
CFR: 
102505367(EGLN1) 102507989(EGLN2) 102516321(EGLN3)
BACU: 
102997608(EGLN3) 103012144(EGLN2) 103012953(EGLN1)
LVE: 
103078947(EGLN2) 103086133(EGLN1) 103088451(EGLN3)
ECB: 
100056635(EGLN3) 100060551(EGLN1)
MYB: 
102248142(EGLN2) 102261310(EGLN3) 102261609(EGLN1)
MYD: 
102752541(EGLN2) 102755440(EGLN1) 102764073(EGLN3)
PALE: 
102881942(EGLN2) 102886969(EGLN3) 102894690(EGLN1)
MDO: 
100013679(EGLN3) 100018431(EGLN2) 100029166(EGLN1)
SHR: 
OAA: 
100081498(EGLN3) 100092885(EGLN1)
GGA: 
423316(EGLN3) 768374
MGP: 
TGU: 
100219039(EGLN3) 100227092(EGLN1)
FAB: 
101814352(EGLN3) 101820070(EGLN1)
PHI: 
102100051(EGLN1) 102112105(EGLN3)
APLA: 
101794957(EGLN1) 101803442(EGLN3)
FPG: 
101915692(EGLN1) 101923024(EGLN3)
FCH: 
102047874(EGLN3)
CLV: 
102092186(EGLN1) 102096357(EGLN3)
ASN: 
102372013(EGLN1) 102383580(EGLN3)
AMJ: 
102560217(EGLN3) 102566486(EGLN1)
PSS: 
102454124(EGLN3) 102462349(EGLN1)
CMY: 
102932309(EGLN3) 102944392(EGLN1)
ACS: 
PBI: 
103048035(EGLN2) 103051641(EGLN1) 103066300(EGLN3)
XLA: 
100036879 100158265(egln2) 446395(egln1)
XTR: 
100145602(egln3) 100487735(egln2) 548714(egln1)
DRE: 
100329385(egln1a) 406602(egln3) 436868(egln1b) 559569
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
102349490(EGLN1) 102353261(EGLN3) 102361918(EGLN2)
CMK: 
BFO: 
CIN: 
SPU: 
DME: 
DPO: 
DAN: 
DER: 
DPE: 
DSE: 
DSI: 
DWI: 
DYA: 
DGR: 
DMO: 
DVI: 
AGA: 
AAG: 
CQU: 
AME: 
413929(GB18380)
NVI: 
TCA: 
656696(Hph)
BMOR: 
API: 
PHU: 
ISC: 
LOA: 
TSP: 
NVE: 
HMG: 
TAD: 
CRE: 
VCN: 
MIS: 
MPP: 
BPG: 
PIF: 
NGD: 
EHX: 
GTT: 
 » show all
Taxonomy
Reference
1  [PMID:11292861]
  Authors
Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim Av, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ
  Title
Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.
  Journal
Science. 292 (2001) 468-72.
  Organism
Homo sapiens
  Sequence
[hsa:112398]
Reference
2  [PMID:11292862]
  Authors
Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr
  Title
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
  Journal
Science. 292 (2001) 464-8.
Reference
3  [PMID:11598268]
  Authors
Bruick RK, McKnight SL
  Title
A conserved family of prolyl-4-hydroxylases that modify HIF.
  Journal
Science. 294 (2001) 1337-40.
  Organism
Homo sapiens
  Sequence
Reference
4  [PMID:11595184]
  Authors
Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ
  Title
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
  Journal
Cell. 107 (2001) 43-54.
  Organism
Homo sapiens
  Sequence
Reference
5  [PMID:12163023]
  Authors
Oehme F, Ellinghaus P, Kolkhof P, Smith TJ, Ramakrishnan S, Hutter J, Schramm M, Flamme I
  Title
Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors.
  Journal
Biochem. Biophys. Res. Commun. 296 (2002) 343-9.
  Organism
Homo sapiens
  Sequence
Reference
6  [PMID:12039559]
  Authors
McNeill LA, Hewitson KS, Gleadle JM, Horsfall LE, Oldham NJ, Maxwell PH, Pugh CW, Ratcliffe PJ, Schofield CJ
  Title
The use of dioxygen by HIF prolyl hydroxylase (PHD1).
  Journal
Bioorg. Med. Chem. Lett. 12 (2002) 1547-50.
  Organism
Homo sapiens
  Sequence
[hsa:112398]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

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