EC               Enzyme                                 

hypoxia-inducible factor-proline dioxygenase;
HIF hydroxylase
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
hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
hypoxia-inducible factor-L-proline;
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007]
hypoxia-inducible factor-trans-4-hydroxy-L-proline;
succinate [CPD:C00042];
CO2 [CPD:C00011]
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.
EC created 2010
K09592  hypoxia-inducible factor prolyl hydroxylase
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)
NLE: 100583623 100584172(EGLN2) 100591967(EGLN3) 100594374(EGLN1)
MCC: 703083(EGLN2) 713410(EGLN1) 717342(EGLN3)
MCF: 101865926(EGLN3) 102119819(EGLN2) 102128342(EGLN1)
CSAB: 103228800(EGLN3) 103230756(EGLN1) 103234719(EGLN2)
RRO: 104670730(EGLN1) 104676100(EGLN2) 104676305(EGLN3)
RBB: 108537828(EGLN1) 108539035(EGLN2) 108544680(EGLN3)
CJC: 100389821(EGLN3) 100397980(EGLN2) 100413526(EGLN1)
SBQ: 101029000(EGLN3) 101045149(EGLN2) 101051675(EGLN1)
MMU: 112405(Egln1) 112406(Egln2) 112407(Egln3)
RNO: 308457(Egln2) 308913(Egln1) 54702(Egln3)
CGE: 100754377 100771495(Egln2) 100772704(Egln1)
NGI: 103738632(Egln3) 103744145(Egln1) 103750775(Egln2)
HGL: 101704717(Egln2) 101709882(Egln1) 101718787(Egln3)
CCAN: 109694610(Egln1) 109697177(Egln3) 109697661(Egln2)
OCU: 100337938(EGLN2) 100354210(EGLN3) 100357337(EGLN1)
TUP: 102482051(EGLN1) 102483132(EGLN2) 102502105(EGLN3)
CFA: 480286(EGLN3) 484495(EGLN2) 488971(EGLN1)
AML: 100465601(EGLN2) 100470632(EGLN3) 100474374(EGLN1)
UMR: 103661051(EGLN2) 103661877(EGLN1) 103680905(EGLN3)
ORO: 101367839(EGLN3) 101368021(EGLN2) 101377787(EGLN1)
FCA: 101082320(EGLN3) 101089964(EGLN1) 101090063(EGLN2)
PTG: 102951182(EGLN3) 102957902(EGLN1) 102958475(EGLN2)
AJU: 106976258(EGLN3) 106979627(EGLN2) 106981639(EGLN1)
BTA: 107131274 534075(EGLN1) 535578(EGLN3) 536763(EGLN2)
BOM: 102280498(EGLN3) 102280646(EGLN2) 102287116(EGLN1)
BIU: 109572227(EGLN2) 109575537(EGLN3)
PHD: 102317356(EGLN2) 102334028(EGLN1) 102335283(EGLN3)
CHX: 102179524(EGLN3) 102189459(EGLN1) 102191264(EGLN2)
OAS: 101114163(EGLN1) 101117367(EGLN3) 101120517(EGLN2)
SSC: 100152368(EGLN3) 100153461(EGLN1) 100523673(EGLN2)
CFR: 102505367(EGLN1) 102507989 102513612(EGLN2) 102516321(EGLN3)
CDK: 105093358(EGLN2) 105094177(EGLN3) 105102153(EGLN1)
BACU: 102997608(EGLN3) 103012144(EGLN2) 103012953(EGLN1)
LVE: 103078947(EGLN2) 103086133(EGLN1) 103088451(EGLN3)
OOR: 101284894(EGLN3) 101288091(EGLN1) 101288571(EGLN2)
ECB: 100056635(EGLN3) 100060551(EGLN1) 100064859(EGLN2)
EPZ: 103553997(EGLN1) 103554984(EGLN3) 103565423(EGLN2)
EAI: 106841256(EGLN3) 106843305(EGLN2) 106846732(EGLN1)
MYB: 102248142(EGLN2) 102261310(EGLN3) 102261609(EGLN1) 106727695
MYD: 102752541(EGLN2) 102755440(EGLN1) 102764073(EGLN3)
HAI: 109374857(EGLN2) 109390367(EGLN3) 109395076(EGLN1)
RSS: 109458032(EGLN2) 109459777(EGLN3) 109461255(EGLN1)
PALE: 102881942(EGLN2) 102886969(EGLN3) 102894690(EGLN1)
LAV: 100672145(EGLN1) 100674039(EGLN3) 100675805(EGLN2)
MDO: 100013679(EGLN3) 100018431(EGLN2) 100029166(EGLN1)
SHR: 100913457(EGLN3) 100929665(EGLN1)
OAA: 100081498(EGLN3) 100092885(EGLN1)
GGA: 423316(EGLN3) 768374(EGLN1)
MGP: 100540578(EGLN1) 100550799(EGLN3)
CJO: 107311390(EGLN1) 107315049(EGLN3)
APLA: 101794957(EGLN1) 101803442(EGLN3)
ACYG: 106031746(EGLN3) 106048487(EGLN1)
TGU: 100219039(EGLN3) 100227092(EGLN1)
GFR: 102036235(EGLN3) 102036815(EGLN1)
FAB: 101814352(EGLN3) 101820070(EGLN1)
PHI: 102100051(EGLN1) 102112105(EGLN3)
PMAJ: 107202314(EGLN1) 107206290(EGLN3)
CCW: 104684300(EGLN1) 104684695(EGLN3)
FPG: 101915692(EGLN1) 101923024(EGLN3)
FCH: 102047874(EGLN3) 102059512(EGLN1)
CLV: 102092186(EGLN1) 102096357(EGLN3)
EGZ: 104131025(EGLN1) 104133309(EGLN3)
AAM: 106483112(EGLN3) 106487314(EGLN1)
ASN: 102372013(EGLN1) 102383580(EGLN3)
AMJ: 102560217(EGLN3) 102566486(EGLN1)
PSS: 102454124(EGLN3) 102462349(EGLN1)
CMY: 102932309(EGLN3) 102944392(EGLN1)
CPIC: 101944959(EGLN3) 101952573(EGLN1)
ACS: 100555054(egln3) 100559436(egln1) 100567728(egln2)
PVT: 110070219(EGLN3) 110075404(EGLN1) 110075601(EGLN2)
PBI: 103048035(EGLN2) 103051641(EGLN1) 103066300(EGLN3)
GJA: 107108842(EGLN3) 107109906(EGLN2) 107123956(EGLN1)
XLA: 100036879(egln3.S) 100127282(egln3.L) 100158265(egln2.L) 108700271(egln2.S) 446395(egln1.S)
XTR: 100145602(egln3) 100487735(egln2) 548714(egln1)
NPR: 108789517(EGLN1) 108791944(EGLN2) 108794163(EGLN3)
DRE: 100329385(egln1a) 406602(egln3) 436868(egln1b) 559569(egln2)
IPU: 108270013(egln3) 108270809(egln1) 108278008
MZE: 101472504 101475861(egln3) 101476165(egln1)
OLA: 101164580 101170367(egln1) 101175282(egln3)
XMA: 102221054 102232168(egln1) 102237645(egln3)
PRET: 103458095(egln3) 103474618 103477256(egln1)
NFU: 107374017(egln3) 107375426(egln1) 107380304
CSEM: 103378094 103382494(egln3) 103387611(egln1)
LCF: 108881163(egln3) 108885792(egln1) 108900822
HCQ: 109516196(egln1) 109526346
BPEC: 110153075(egln3) 110154109 110157004(egln1)
ELS: 105006344(egln1) 105012182 105012318(egln1) 105023611(egln3)
LCM: 102349490(EGLN1) 102353261(EGLN3) 102361918(EGLN2)
CMK: 103178556(egln3) 103178599 103178883(egln1)
CIN: 100180463
SPU: 578715
DME: Dmel_CG44015(Hph)
DSI: Dsimw501_GD19772(Dsim_GD19772)
MDE: 101890432
AAG: 5576110
AME: 413929
BIM: 100747684
AEC: 105151857
ACEP: 105617596
PBAR: 105430352
HST: 105185148
CFO: 105255753
PGC: 109858347
NVI: 100119129
TCA: 656696(Hph)
DPA: 109544161
NVL: 108557275
BMOR: 101739524
PMAC: 106721680
PRAP: 110991997
PXY: 105384261
API: 100169314
DNX: 107162127
ZNE: 110840473
FCD: 110844239
TUT: 107367778
CEL: CELE_F22E12.4(egl-9)
CBR: CBG09602(Cbr-egl-9)
TSP: Tsp_03219
OBI: 106873167
HMG: 100209808
SMIN: v1.2.034866.t1(symbB.v1.2.034866.t1)
 » show all
1  [PMID:11292861]
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
Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.
Science. 292 (2001) 468-72.
2  [PMID:11292862]
Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
Science. 292 (2001) 464-8.
3  [PMID:11598268]
Bruick RK, McKnight SL
A conserved family of prolyl-4-hydroxylases that modify HIF.
Science. 294 (2001) 1337-40.
4  [PMID:11595184]
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
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
Cell. 107 (2001) 43-54.
5  [PMID:12163023]
Oehme F, Ellinghaus P, Kolkhof P, Smith TJ, Ramakrishnan S, Hutter J, Schramm M, Flamme I
Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors.
Biochem. Biophys. Res. Commun. 296 (2002) 343-9.
6  [PMID:12039559]
McNeill LA, Hewitson KS, Gleadle JM, Horsfall LE, Oldham NJ, Maxwell PH, Pugh CW, Ratcliffe PJ, Schofield CJ
The use of dioxygen by HIF prolyl hydroxylase (PHD1).
Bioorg. Med. Chem. Lett. 12 (2002) 1547-50.
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