KEGG ENZYME: 1.14.11.30

ENZYME: 1.14.11.30

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

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.

History

EC 1.14.11.30 created 2010

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)

PPYG:

129045315(HIF1AN)

NLE:	100604492(HIF1AN)

HMH:	116485002(HIF1AN)

SSYN:

129467450(HIF1AN)

MCC:	710425(HIF1AN)

MCF:	102123484(HIF1AN)

MTHB:

126963077

MNI:	105478393(HIF1AN)

CSAB:

103216391(HIF1AN)

CATY:

105581839(HIF1AN)

PANU:

101002735(HIF1AN)

TGE:	112630967(HIF1AN)

MLEU:

105537751(HIF1AN)

RRO:	104656480(HIF1AN)

RBB:	108535279(HIF1AN)

TFN:	117068379(HIF1AN)

PTEH:

111538810(HIF1AN)

CANG:

105507140(HIF1AN)

CJC:	100415279(HIF1AN)

SBQ:	101041386(HIF1AN)

CIMI:

108306361(HIF1AN)

ANAN:

105708187(HIF1AN)

CSYR:

103252625(HIF1AN)

MMUR:

105873644(HIF1AN)

LCAT:

123650125(HIF1AN)

PCOQ:

105824309(HIF1AN)

OGA:	100947331(HIF1AN)

MMU:	319594(Hif1an)

MCAL:

110286051(Hif1an)

MPAH:

110324633(Hif1an)

RNO:	309434(Hif1an)

MCOC:

116103898(Hif1an)

ANU:	117723685(Hif1an)

MUN:	110556051(Hif1an)

CGE:	100752342(Hif1an)

MAUA:

101836236(Hif1an)

PROB:

127233505(Hif1an)

PLEU:

114708116(Hif1an)

MORG:

121453978(Hif1an)

MFOT:

126503813

AAMP:

119811745(Hif1an)

NGI:	103743986(Hif1an)

HGL:	101715790(Hif1an)

CPOC:

100723844(Hif1an)

CCAN:

109685931(Hif1an)

DORD:

105986733(Hif1an)

DSP:	122115749(Hif1an)

PLOP:

125346156(Hif1an)

NCAR:

124984627

MMMA:

107149805(Hif1an)

OCU:

100347080

OPI:	101530345(HIF1AN)

TUP:	102471470(HIF1AN)

GVR:	103595678(HIF1AN)

CFA:	609221(HIF1AN)

CLUD:

112672200(HIF1AN)

VVP:	112914909(HIF1AN)

VLG:	121482064(HIF1AN)

NPO:	129493737(HIF1AN)

AML:	100484876(HIF1AN)

UMR:	103677605(HIF1AN)

UAH:	113251834(HIF1AN)

UAR:	123795869(HIF1AN)

ELK:

111145240

LLV:

125085170

MPUF:

101670598(HIF1AN) 106003906

MNP:	132016702(HIF1AN)

MLK:	131828541(HIF1AN)

NVS:	122899286(HIF1AN)

ORO:	101367069(HIF1AN)

EJU:	114205221(HIF1AN)

ZCA:	113922416(HIF1AN)

MLX:	118025021(HIF1AN)

NSU:	110589203(HIF1AN)

LWW:	102738370(HIF1AN)

FCA:	101091901(HIF1AN)

PYU:	121037113(HIF1AN)

PCOO:

112854606(HIF1AN)

PBG:	122493141(HIF1AN)

PVIV:

125148282(HIF1AN)

LRUF:

124507065

PTG:	102952057(HIF1AN)

PPAD:

109272772(HIF1AN)

PUC:

125933428

AJU:

106966868

HHV:	120243183(HIF1AN)

BTA:	520864(HIF1AN)

BOM:	102285023(HIF1AN)

BIU:	109579158(HIF1AN)

BBUB:

102412343(HIF1AN)

BBIS:

105002709(HIF1AN)

CHX:	102182662(HIF1AN)

OAS:	101122066(HIF1AN)

BTAX:

128068025(HIF1AN)

ODA:	120873672(HIF1AN)

CCAD:

122440566 122446041(HIF1AN)

MBEZ:

129555440(HIF1AN)

SSC:	100155854(HIF1AN)

CFR:	102504253(HIF1AN)

CBAI:

105081739(HIF1AN)

CDK:	105084325(HIF1AN)

VPC:	102532041(HIF1AN)

BACU:

103010817(HIF1AN)

BMUS:

118882527(HIF1AN) 118899557

LVE:	103087616(HIF1AN)

OOR:	101282716(HIF1AN) 101283131

DLE:	111172388(HIF1AN)

PCAD:

102994002(HIF1AN)

PSIU:

116741871(HIF1AN)

NASI:

112392955(HIF1AN)

ECB:	100070337(HIF1AN)

EPZ:	103562515(HIF1AN)

EAI:	106846748(HIF1AN)

MYB:	102258997(HIF1AN)

MYD:	102758329(HIF1AN)

MMYO:

118669846(HIF1AN)

MLF:	102428527(HIF1AN)

MDT:	132214238(HIF1AN)

PKL:	118719412(HIF1AN)

EFUS:

103288480(HIF1AN)

MNA:	107542595(HIF1AN)

DRO:	112300387(HIF1AN)

SHON:

118999511(HIF1AN)

AJM:	119059658(HIF1AN)

PDIC:

114496025(HIF1AN)

PHAS:

123828715(HIF1AN)

MMF:	118632049(HIF1AN)

PPAM:

129077117(HIF1AN)

HAI:	109379673(HIF1AN)

RFQ:	117035922(HIF1AN)

PALE:

102898816(HIF1AN)

PGIG:

120609200(HIF1AN)

PVP:	105304628(HIF1AN)

RAY:	107499768(HIF1AN)

MJV:	108409589(HIF1AN)

TOD:	119233533(HIF1AN)

SARA:

101544457(HIF1AN)

SETR:

125994787(HIF1AN)

LAV:	100665502(HIF1AN)

TMU:

101343053

ETF:	101664108(HIF1AN)

DNM:	101426098(HIF1AN)

MDO:	100010508(HIF1AN)

GAS:	123236234(HIF1AN)

SHR:	100932046(HIF1AN)

AFZ:

127551476

PCW:	110194380(HIF1AN)

TVP:	118828817(HIF1AN)

OAA:	100084505(HIF1AN)

GGA:	428952(HIF1AN)

PCOC:

116234464(HIF1AN)

MGP:	100547017(HIF1AN)

CJO:	107315863(HIF1AN)

TPAI:

128078167(HIF1AN)

LMUT:

125693420(HIF1AN)

NMEL:

110399772(HIF1AN)

APLA:

101796702(HIF1AN)

ACYG:

106029735(HIF1AN)

CATA:

118250381(HIF1AN)

AFUL:

116491443(HIF1AN)

TGU:	100224185(HIF1AN)

LSR:	110480119(HIF1AN)

SCAN:

103814193(HIF1AN)

PMOA:

120501999(HIF1AN)

OTC:	121341776(HIF1AN)

PRUF:

121350159(HIF1AN)

GFR:	102039688(HIF1AN)

FAB:	101815471(HIF1AN)

OMA:	130254618(HIF1AN)

PHI:	102110633(HIF1AN)

PMAJ:

107207042(HIF1AN)

CCAE:

111931112(HIF1AN) 111943060

CCW:	104697935(HIF1AN)

CBRC:

103624589(HIF1AN)

ETL:	114054698(HIF1AN)

ZAB:	102064287(HIF1AN)

ZLE:	135449583(HIF1AN)

ACHL:

103806919(HIF1AN)

SVG:	106852618(HIF1AN)

MMEA:

130578787(HIF1AN)

HRT:	120756020(HIF1AN)

SATI:

136364222(HIF1AN)

FPG:	101910571(HIF1AN)

FCH:	102050862(HIF1AN)

CCRI:

104155896(HIF1AN)

NNT:	104400365(HIF1AN)

SHAB:

115607903(HIF1AN)

ACUN:

113481527(HIF1AN)

TALA:

104356952(HIF1AN)

ACHC:

115348129(HIF1AN)

HALD:

104324453(HIF1AN)

HLE:	104831876(HIF1AN)

AGEN:

126043090

GCL:

127017975

CSTI:

104551188(HIF1AN)

LDI:	104343294(HIF1AN)

MNB:	103772011(HIF1AN)

DPUB:

104297693(HIF1AN)

AVIT:

104270371(HIF1AN)

BRHI:

104494172(HIF1AN)

EGZ:	104129025(HIF1AN)

NNI:	104014094(HIF1AN)

PCRI:

104032321(HIF1AN)

PCAO:

104040151(HIF1AN)

PADL:

103915599(HIF1AN)

AFOR:

103897819(HIF1AN)

FGA:	104073767(HIF1AN)

GSTE:

104259221(HIF1AN)

CLV:	102094216(HIF1AN)

MUI:	104540658(HIF1AN)

PGUU:

104466469(HIF1AN)

PLET:

104626915(HIF1AN)

EHS:	104514179(HIF1AN)

CMAC:

104486962(HIF1AN)

CUCA:

104067978(HIF1AN)

TEO:	104379554(HIF1AN)

BREG:

104636084(HIF1AN)

OHA:	104339431(HIF1AN)

ACAR:

104526719(HIF1AN)

CPEA:

104391510(HIF1AN)

CVF:	104289815(HIF1AN)

RTD:	128911446(HIF1AN)

AAM:	106497781(HIF1AN)

AROW:

112967510(HIF1AN)

NPD:	112956786(HIF1AN)

TGT:	104573062(HIF1AN)

DNE:	112980206(HIF1AN)

SCAM:

104141814(HIF1AN)

ASN:	102372847(HIF1AN)

AMJ:	102557843(HIF1AN)

CPOO:

109324092(HIF1AN)

GGN:	109287427(HIF1AN)

PSS:	102461331(HIF1AN)

CMY:	102940361(HIF1AN)

CCAY:

125639785(HIF1AN)

DCC:	119858788(HIF1AN)

CPIC:

101950170(HIF1AN)

TST:	117880361(HIF1AN)

CABI:

116823607(HIF1AN)

MRV:	120368981(HIF1AN)

ACS:	100564872(hif1an)

ASAO:

132771334 132771335

PVT:	110077766(HIF1AN)

SUND:

121925860(HIF1AN)

PBI:	103049844(HIF1AN)

PMUR:

107292978(HIF1AN)

CTIG:

120308925(HIF1AN)

TSR:	106551040(HIF1AN)

PGUT:

117676315(HIF1AN)

APRI:

131200538(HIF1AN)

PTEX:

113445375(HIF1AN)

NSS:	113415395(HIF1AN)

VKO:	123018291(HIF1AN)

PMUA:

114597002(HIF1AN)

PRAF:

128413669(HIF1AN)

ZVI:	118096425(HIF1AN)

HCG:	128350046(HIF1AN)

GJA:	107110489(HIF1AN)

STOW:

125437952(HIF1AN)

EMC:	129332747(HIF1AN)

XLA:	108696241(hif1an.L) 432095(hif1an.S)

XTR:	394511(hif1an)

NPR:	108791896(HIF1AN)

RTEM:

120947211(HIF1AN)

BBUF:

121004796(HIF1AN)

BGAR:

122941622(HIF1AN)

MUO:	115470397(HIF1AN)

GSH:	117358862(HIF1AN)

DRE:	373126(hif1an)

SRX:	107707391 107716346

SANH:

107668772 107673917

SGH:	107585304 107588638

CCAR:

109056102 109100806(hif1an)

CAUA:

113096118 113096513 113112650

CGIB:

127970054 128026141

PTET:

122356626(hif1an)

LROH:

127175300(hif1an)

OMC:	131552516(hif1an)

PPRM:

120479566(hif1an)

RKG:	130077613(hif1an)

MAMB:

125277009(hif1an)

CIDE:

127524978

CERY:

137020615(hif1an)

MASI:

127412251 127414035

TROS:

130559684(hif1an)

TDW:	130431668(hif1an)

MANU:

129416227(hif1an)

IPU:	100304654(hif1an)

IFU:	128605659(hif1an)

PHYP:

113539085(hif1an)

SMEO:

124401561(hif1an)

TFD:	113639756(hif1an)

TVC:	132847336(hif1an)

TRN:	134315170(hif1an)

AMEX:

103021617(hif1an)

CMAO:

118810449(hif1an)

EEE:	113580956(hif1an)

CHAR:

105910146(hif1an)

TRU:	101073285(hif1an)

TFS:	130533859(hif1an)

TNG:	GSTEN00016444G001

LCO:	104930472(hif1an)

NCC:	104944324(hif1an)

TBEN:

117499695(hif1an)

CGOB:

115020453(hif1an)

PGEO:

117459534(hif1an)

GACU:

117538171(hif1an)

EMAC:

134858659(hif1an)

ELY:	117248213(hif1an)

EFO:	125903555(hif1an)

PLEP:

121954711(hif1an)

SLUC:

116054569(hif1an)

ECRA:

117960817(hif1an)

ESP:	116705699(hif1an)

PFLV:

114571850(hif1an)

GAT:	120820609(hif1an)

PPUG:

119213875(hif1an)

AFB:	129092142(hif1an)

CLUM:

117743927(hif1an)

PSWI:

130207469(hif1an)

MSAM:

119917049(hif1an)

SCHU:

122884450(hif1an)

CUD:	121511507(hif1an)

ALAT:

119033484(hif1an)

ASTR:

137603693(hif1an)

MZE:	101486879(hif1an)

ONL:	100691020(hif1an)

OAU:	116316620(hif1an)

OLA:	101156274(hif1an)

OML:	112161382(hif1an)

CSAI:

133463595(hif1an)

XMA:	102235402(hif1an)

XCO:	114137999(hif1an)

XHE:	116713223(hif1an)

PRET:

103476845(hif1an)

PFOR:

103133483(hif1an)

PLAI:

106961118(hif1an)

PMEI:

106904405(hif1an)

GAF:	122843020(hif1an)

PPRL:

129359878(hif1an)

CVG:	107094647(hif1an)

CTUL:

119788541(hif1an)

GMU:	124859545(hif1an)

NFU:	107375913(hif1an)

KMR:	108242543(hif1an)

ALIM:

106537216(hif1an)

NWH:	119419493(hif1an)

AOCE:

111573894(hif1an)

MCEP:

125018793(hif1an)

CSEM:

103387232(hif1an)

POV:	109636467(hif1an)

SSEN:

122781608(hif1an)

HHIP:

117775552(hif1an)

HSP:	118118800(hif1an)

PPLT:

128453383(hif1an)

SMAU:

118283559(hif1an)

LCF:	108880378 108897266

SDU:	111235212(hif1an)

SLAL:

111670027(hif1an)

XGL:	120796342(hif1an)

HCQ:	109509915(hif1an)

SSCV:

125978367

SBIA:

133509389(hif1an)

PEE:	133409473(hif1an)

PTAO:

133485462(hif1an)

BPEC:

110173607(hif1an)

MALB:

109961948(hif1an)

BSPL:

114870434(hif1an)

SJO:	128373056(hif1an)

SASA:

106577208 106608512

STRU:

115153351 115193595

OTW:	112253174 112256023

OMY:	101268916(fih1) 110502616

OGO:	124038347 124041130(hif1an)

ONE:	115113111(hif1an) 115115286 115115301

OKI:	109890050 109899802

OKE:	118369848(hif1an) 118398936

SALP:

111952003 111977452

SNH:	120017746 120046624

CCLU:

121553675 121574165

ELS:	105021418(hif1an)

SFM:	108925770(hif1an)

PKI:	111858910(hif1an)

AANG:

118218078(hif1an)

LOC:	102696504(hif1an)

PSPA:

121321504(hif1an) 121325669

ARUT:

117415922 117418343

PSEX:

120541160(hif1an)

LCM:	102346962(HIF1AN)

CMK:	103182440(hif1an)

RTP:	109918423(hif1an)

CPLA:

122541779(hif1an)

HOC:	132835104(hif1an)

LERI:

129713021(hif1an)

PMRN:

116940154(HIF1AN)

LRJ:	133350743(HIF1AN)

BFO:

118411368

BBEL:

109478301

CIN:

100179426

SCLV:

120346944

LPIC:

129281352 129281523

APLC:

110973644

ARUN:

117303703

AJC:

117122894

TCA:	664369(HIF)

SOY:	115883550 115890168

AGRG:

126735015

ATD:

109600047

CSET:

123311440

AGB:

108914580

LDC:

111514390

DVV:

114325798

NVL:

108569277

PPYR:

116180589

OTU:

111425717

CCRN:

123297846

API:

100162022

DNX:

107173162

AGS:

114125548

RMD:

113560576

ACOO:

126838707

DVT:

126900466

BTAB:

109039905

DCI:

103507567

CLEC:

106665541

HHAL:

106691535

NLU:

111048055

HVI:

124358927

MQU:

128987103

PHU:	Phum_PHUM407820

FOC:

113205097

TPAL:

117647619

ZNE:

110830997

CSEC:

111867209

SGRE:

126335079

BROR:

134539486

IEL:

124160568

FCD:

110851748

PVM:

113800549

PJA:

122263765

PCHN:

125038294

PMOO:

119587116

HAME:

121880351

PCLA:

123745304

CQD:

128685236

PTRU:

123509206

ESN:

127003291

MNZ:

135221812

MRJ:

136844397

HAZT:

108664674

DSV:

119434826

RSAN:

119405903

RMP:

119177212

CVS:

136979293

LPOL:

106457664 106459917 106462179

PMEO:

129592790

HRO:	HELRODRAFT_189263

LGI:	LOTGIDRAFT_220114

PVUL:

126810610

PCAN:

112562890

BGT:

106054937

GAE:

121379453

HRF:

124149320

HRJ:

124277181

CRG:

105334801

CANU:

128166430

CVN:

111121306

OED:

125670892

MYI:

110450414

PMAX:

117322963

MCAF:

127708708

MMER:

123562000

RPHI:

132713858

DPOL:

127848318

MAEA:

128211074

OBI:

106870719

OSN:

115220825

LJP:

135478724

LAK:	106155210 106165936

LLON:

135494242

NVE:	5501215 5501636

EPA:	110236639 110249031

ATEN:

116288999 116295356

ADF:

107332369

AMIL:

114965326 114965450

PDAM:

113677270 113685250

SPIS:

111344428 111344885

DGT:	114524952 114526899

XEN:

124458906

HSY:

130654084

RES:

135696508

AQU:

100639620

CSL:	COCSUDRAFT_59858

MBR:	MONBRDRAFT_26110

SRE:	PTSG_00189

EHX:	EMIHUDRAFT_199541 EMIHUDRAFT_216215 EMIHUDRAFT_235592 EMIHUDRAFT_314391 EMIHUDRAFT_434665 EMIHUDRAFT_443728

GTT:	GUITHDRAFT_162927

DFS:	HGD76_20440

» show all

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 15:2675-86 (2001)
DOI:10.1101/gad.924501

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 277:26351-5 (2002)
DOI:10.1074/jbc.C200273200

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 99:15351-6 (2002)
DOI:10.1073/pnas.202614999

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 295:858-61 (2002)
DOI:10.1126/science.1068592

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 279:9899-904 (2004)
DOI:10.1074/jbc.M312254200

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 278:1802-6 (2003)
DOI:10.1074/jbc.C200644200

Sequence

[hsa:55662]

Other DBs

ExplorEnz - The Enzyme Database:

1.14.11.30

IUBMB Enzyme Nomenclature:

1.14.11.30

ExPASy - ENZYME nomenclature database:

1.14.11.30

BRENDA, the Enzyme Database:

1.14.11.30

DBGET integrated database retrieval system