HIF1N_DANRE
ID HIF1N_DANRE Reviewed; 344 AA.
AC P59723; B8A5K4;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Hypoxia-inducible factor 1-alpha inhibitor;
DE EC=1.14.11.30;
DE EC=1.14.11.n4;
DE AltName: Full=Hypoxia-inducible factor asparagine hydroxylase;
GN Name=hif1an; ORFNames=si:rp71-68n3.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Hydroxylates a specific Asn residue in the C-terminal
CC transactivation domain (CAD) of HIF-1 alpha. The hydroxylation prevents
CC interaction of HIF-1 with transcriptional coactivators. Also
CC hydroxylates specific Asn, Asp and His residues within ankyrin repeat
CC domain-containing proteins. {ECO:0000250|UniProtKB:Q9NWT6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-asparaginyl-[hypoxia-inducible factor alpha
CC subunit] + O2 = (3S)-3-hydroxy-L-asparaginyl-[hypoxia-inducible
CC factor alpha subunit] + CO2 + succinate; Xref=Rhea:RHEA:54268,
CC Rhea:RHEA-COMP:13833, Rhea:RHEA-COMP:13834, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:50347, ChEBI:CHEBI:138107; EC=1.14.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-histidyl-[ankyrin-repeat domain protein] +
CC O2 = (3S)-3-hydroxy-L-histidyl-[ankyrin-repeat domain protein] + CO2
CC + succinate; Xref=Rhea:RHEA:54264, Rhea:RHEA-COMP:13836, Rhea:RHEA-
CC COMP:13837, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:30031, ChEBI:CHEBI:138021;
CC EC=1.14.11.n4;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-asparaginyl-[ankyrin-repeat domain protein]
CC + O2 = (3S)-3-hydroxy-L-asparaginyl-[ankyrin-repeat domain protein] +
CC CO2 + succinate; Xref=Rhea:RHEA:54272, Rhea:RHEA-COMP:13838,
CC Rhea:RHEA-COMP:13839, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:50347,
CC ChEBI:CHEBI:138107; EC=1.14.11.n4;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-aspartyl-[ankyrin-repeat domain protein] +
CC O2 = (3S)-3-hydroxy-L-aspartyl-[ankyrin-repeat domain protein] + CO2
CC + succinate; Xref=Rhea:RHEA:54280, Rhea:RHEA-COMP:13843, Rhea:RHEA-
CC COMP:13844, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29961, ChEBI:CHEBI:30031, ChEBI:CHEBI:138111;
CC EC=1.14.11.n4;
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q9NWT6};
CC -!- SUBUNIT: Homodimer; homodimerization is essential for catalytic
CC activity. {ECO:0000250|UniProtKB:Q9NWT6}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NWT6}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9NWT6}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q9NWT6}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX548172; CAX13993.1; -; Genomic_DNA.
DR EMBL; BC044475; AAH44475.1; -; mRNA.
DR RefSeq; NP_958904.1; NM_201496.1.
DR AlphaFoldDB; P59723; -.
DR SMR; P59723; -.
DR BioGRID; 88738; 3.
DR STRING; 7955.ENSDARP00000042048; -.
DR PaxDb; P59723; -.
DR Ensembl; ENSDART00000042049; ENSDARP00000042048; ENSDARG00000031915.
DR GeneID; 373126; -.
DR KEGG; dre:373126; -.
DR CTD; 55662; -.
DR ZFIN; ZDB-GENE-030826-19; hif1an.
DR eggNOG; KOG2132; Eukaryota.
DR GeneTree; ENSGT00940000157409; -.
DR HOGENOM; CLU_016785_3_0_1; -.
DR InParanoid; P59723; -.
DR OMA; CLYPHPV; -.
DR OrthoDB; 1385616at2759; -.
DR TreeFam; TF329609; -.
DR Reactome; R-DRE-1234174; Cellular response to hypoxia.
DR PRO; PR:P59723; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 13.
DR Bgee; ENSDARG00000031915; Expressed in early embryo and 40 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IBA:GO_Central.
DR GO; GO:0071532; F:ankyrin repeat binding; IBA:GO_Central.
DR GO; GO:0031406; F:carboxylic acid binding; ISS:UniProtKB.
DR GO; GO:0008198; F:ferrous iron binding; ISS:UniProtKB.
DR GO; GO:0102113; F:hypoxia-inducible factor-asparagine oxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0036140; F:peptidyl-asparagine 3-dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0036139; F:peptidyl-histidine dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IBA:GO_Central.
DR GO; GO:1901343; P:negative regulation of vasculature development; IDA:ZFIN.
DR GO; GO:0042265; P:peptidyl-asparagine hydroxylation; ISS:UniProtKB.
DR GO; GO:0042264; P:peptidyl-aspartic acid hydroxylation; ISS:UniProtKB.
DR GO; GO:0036138; P:peptidyl-histidine hydroxylation; ISS:UniProtKB.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; IGI:ZFIN.
DR Gene3D; 1.10.287.1010; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR041667; Cupin_8.
DR InterPro; IPR027445; FIH-1.
DR InterPro; IPR027452; FIH-1_dom_II.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR PANTHER; PTHR12461:SF80; PTHR12461:SF80; 1.
DR Pfam; PF13621; Cupin_8; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Dioxygenase; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Reference proteome; Transcription;
KW Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT CHAIN 2..344
FT /note="Hypoxia-inducible factor 1-alpha inhibitor"
FT /id="PRO_0000083973"
FT DOMAIN 133..303
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 136
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 143
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 173..174
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 187
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 190
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 192..194
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 192
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 196
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 205
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 229..230
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 270
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 285
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 291
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT BINDING 312
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT SITE 331
FT /note="Important for dimer formation"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWT6"
FT CONFLICT 17
FT /note="D -> G (in Ref. 2; AAH44475)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="E -> G (in Ref. 2; AAH44475)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="D -> E (in Ref. 2; AAH44475)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 344 AA; 39992 MW; 8045A5D71679410F CRC64;
MAETDGAAAF TELRDPDWDE SQLRQYTFPT RQIPRLSHTD PRAEVLINNE EPVVLTDTSL
VYPALKWDIP YLQENIGNGD FSVYIAENHK FLYYDEKKMV NFQDFVPKSR RIEMKFSEFV
DKMHQTEEQG GKGRVYLQQT LNDTVGRKIV VDFLGFNWNW INKQQAKRNW GPLTSNLLLI
GMEGNVTPAH YDEQQNFFAQ IKGHKRCILF PPDQFDCLYP YPVHHPCDRQ SQVDFENPDY
DKFPNFKNAV GYEAVVGPGD VLYIPMYWWH HIESLLNGGE TITVNFWYKG APTPKRIEYP
LKAHQKVAIM RNIEKMLGEA LGDPHEVGPL LNMMIKGRYD HGLS
