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Reviewed, UniProtKB/Swiss-Prot Q9NWT6 (HIF1N_HUMAN)

Last modified February 9, 2010. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Hypoxia-inducible factor 1-alpha inhibitor
    EC=1.14.11.16
Alternative name(s):
    Hypoxia-inducible factor asparagine hydroxylase
    Factor inhibiting HIF-1
      Short name=FIH-1
Gene names
Name: HIF1AN
Synonyms: FIH1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length349 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Ref.6 Ref.7

Catalytic activity

Peptide L-aspartate + 2-oxoglutarate + O2 = peptide 3-hydroxy-L-aspartate + succinate + CO2. Ref.6 Ref.7

Cofactor

Iron.

Subunit structure

Homodimer. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Ref.1 Ref.9

Subcellular location

Nucleus Potential.

Sequence similarities

Contains 1 JmjC domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HIF1AQ166651EBI-745632,EBI-447269

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 349348Hypoxia-inducible factor 1-alpha inhibitor
PRO_0000083974

Regions

Domain142 – 312171JmjC
Region2 – 349348Interaction with VHL
Region126 – 349224Interaction with HIF1A

Sites

Metal binding1991Iron; catalytic
Metal binding2011Iron; catalytic
Metal binding2791Iron; catalytic
Binding site14512-oxoglutarate
Binding site19612-oxoglutarate
Binding site21412-oxoglutarate

Amino acid modifications

Modified residue21N-acetylalanine Ref.8

Natural variations

Natural variant411P → A: dbSNP rs2295778.
VAR_051028

Experimental info

Mutagenesis1991H → A: Prevents suppression of HIF CAD activity. Ref.6
Mutagenesis2011D → A: Prevents suppression of HIF CAD activity. Ref.6
Sequence conflict101A → T in BAA91291. Ref.2
Sequence conflict281D → H in BAA91291. Ref.2
Sequence conflict1561R → G in BAA91291. Ref.2

Secondary structure

.............................................................. 349
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NWT6-1 [UniParc].

Last modified June 16, 2003. Version 2.
Checksum: 96A033BA7B3BD8C7

FASTA34940,285
        10         20         30         40         50         60 
MAATAAEAVA SGSGEPREEA GALGPAWDES QLRSYSFPTR PIPRLSQSDP RAEELIENEE 

        70         80         90        100        110        120 
PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF LYYDEKKMAN FQNFKPRSNR 

       130        140        150        160        170        180 
EEMKFHEFVE KLQDIQQRGG EERLYLQQTL NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG 

       190        200        210        220        230        240 
QLTSNLLLIG MEGNVTPAHY DEQQNFFAQI KGYKRCILFP PDQFECLYPY PVHHPCDRQS 

       250        260        270        280        290        300 
QVDFDNPDYE RFPNFQNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA 

       310        320        330        340 
PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN 

« Hide

References

« Hide 'large scale' references
[1]"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity."
Mahon P.C., Hirota K., Semenza G.L.
Genes Dev. 15:2675-2686(2001) [PubMed: 11641274] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH HIF1A; VHL AND HISTONE DEACETYLASES.
Tissue: Brain.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed: 15164054] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Muscle.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-349.
Tissue: Melanoma.
[6]"FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor."
Lando D., Peet D.J., Gorman J.J., Whelan D.A., Whitelaw M.L., Bruick R.K.
Genes Dev. 16:1466-1471(2002) [PubMed: 12080085] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF HIS-199 AND ASP-201.
[7]"Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family."
Hewitson K.S., McNeill L.A., Riordan M.V., Tian Y.-M., Bullock A.N., Welford R.W., Elkins J.M., Oldham N.J., Bhattacharya S., Gleadle J.M., Ratcliffe P.J., Pugh C.W., Schofield C.J.
J. Biol. Chem. 277:26351-26355(2002) [PubMed: 12042299] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[9]"Structure of factor-inhibiting hypoxia-inducible factor 1: an asparaginyl hydroxylase involved in the hypoxic response pathway."
Dann C.E. III, Bruick R.K., Deisenhofer J.
Proc. Natl. Acad. Sci. U.S.A. 99:15351-15356(2002) [PubMed: 12432100] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), SUBUNIT.
[10]"Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha."
Elkins J.M., Hewitson K.S., McNeill L.A., Seibel J.F., Schlemminger I., Pugh C.W., Ratcliffe P.J., Schofield C.J.
J. Biol. Chem. 278:1802-1806(2003) [PubMed: 12446723] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH 786-826 OF HIF1A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF395830 mRNA. Translation: AAL27308.1.
AK000622 mRNA. Translation: BAA91291.1.
AL133352 Genomic DNA. Translation: CAH73566.1.
BC007719 mRNA. Translation: AAH07719.1.
AL359615 mRNA. Translation: CAB94885.1.
IPIIPI00941238.
PIRT50633.
RefSeqNP_060372.2.
UniGeneHs.500788

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H2KX-ray2.15A1-349[»]
1H2LX-ray2.25A1-349[»]
1H2MX-ray2.50A1-349[»]
1H2NX-ray2.84A1-349[»]
1IZ3X-ray2.80A1-349[»]
1MZEX-ray2.20A1-349[»]
1MZFX-ray2.40A1-349[»]
1YCIX-ray2.70A1-349[»]
2CGNX-ray2.40A1-349[»]
2CGOX-ray2.30A1-349[»]
2ILMX-ray2.30A1-349[»]
2W0XX-ray2.12A1-349[»]
3D8CX-ray2.10A11-349[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ9NWT6. 5 interactions.
STRINGQ9NWT6.

Proteomic databases

PRIDEQ9NWT6.

Genome annotation databases

EnsemblENST00000299163; ENSP00000299163; ENSG00000166135; Homo sapiens. [Genome view]
ENST00000442724; ENSP00000399734; ENSG00000166135; Homo sapiens. [Genome view]
GeneID55662.
KEGGhsa:55662.
UCSCuc001krj.2. human.

Organism-specific databases

CTD55662.
GeneCardsGC10P102285.
H-InvDBHIX0009127.
HGNCHGNC:17113. HIF1AN.
MIM606615. gene.
PharmGKBPA29284.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG05011.
HOVERGENQ9NWT6.
InParanoidQ9NWT6.
OrthoDBEOG9M682Z.
PhylomeDBQ9NWT6.

Enzyme and pathway databases

BRENDA1.14.11.16. 247.
Pathway_Interaction_DBhif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.

Gene expression databases

ArrayExpressQ9NWT6.
BgeeQ9NWT6.
CleanExHS_HIF1AN.
GenevestigatorQ9NWT6.
GermOnlineENSG00000166135. Homo sapiens.

Family and domain databases

InterProIPR003347. TF_JmjC_AAH.
[Graphical view]
SMARTSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio60403.
SOURCESearch...

Entry information

Entry nameHIF1N_HUMAN
AccessionPrimary (citable) accession number: Q9NWT6
Secondary accession number(s): Q5W147, Q969Q7, Q9NPV5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: February 9, 2010
This is version 83 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents