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Q9NWT6 (HIF1N_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hypoxia-inducible factor 1-alpha inhibitor

EC=1.14.11.30
EC=1.14.11.n4
Alternative name(s):
Factor inhibiting HIF-1
Short name=FIH-1
Hypoxia-inducible factor asparagine hydroxylase
Gene names
Name:HIF1AN
Synonyms:FIH1
OrganismHomo sapiens (Human) [Reference 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. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. Ref.7 Ref.8 Ref.12 Ref.13 Ref.15 Ref.26 Ref.31 Ref.32

Catalytic activity

Hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2. Ref.7 Ref.8 Ref.10

Ankyrin-repeat-L-histidine + 2-oxoglutarate + O2 = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CO2. Ref.7 Ref.8 Ref.10

Cofactor

Fe2+ ion.

Subunit structure

Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with APBA3; binding inhibits HIF1AN binding to HIF1A. Interacts with TNKS2. Interacts with PPP1R12A. Interacts with ASB4 By similarity. Interacts with UBE3A. Ref.1 Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.18 Ref.21 Ref.23 Ref.26 Ref.32

Subcellular location

Nucleus. Cytoplasm. Cytoplasmperinuclear region. Note: Mainly cytoplasmic localization, but interaction with NOTCH1 results in nuclear localization and interaction with ABPA3 results in perinuclear localization in macrophages. Ref.11 Ref.13 Ref.16

Sequence similarities

Contains 1 JmjC domain.

Biophysicochemical properties

Kinetic parameters:

The kinetic constants are determined for the recombinant FLAG-His-tagged protein.

KM=100 µM for HIF1A (788-822) peptide Ref.10

KM=160 µM for HIF2A (832-866) peptide

KM=0.5 µM for Fe2+

KM=25 µM for 2-oxoglutarate

KM=260 µM for ascorbate

KM=90 µM for O2

Mass spectrometry

Molecular mass is 40566 Da from positions 1 - 349. Determined by ESI. Ref.9

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   LigandIron
Metal-binding
Zinc
   Molecular functionDioxygenase
Oxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to hypoxia

Traceable author statement. Source: Reactome

negative regulation of Notch signaling pathway

Inferred from direct assay Ref.13. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

Inferred from direct assay Ref.1. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay Ref.7PubMed 12215170. Source: UniProtKB

peptidyl-asparagine hydroxylation

Inferred from direct assay Ref.7PubMed 12215170Ref.11Ref.32. Source: UniProtKB

peptidyl-aspartic acid hydroxylation

Inferred from direct assay Ref.32. Source: UniProtKB

peptidyl-histidine hydroxylation

Inferred from direct assay Ref.31. Source: UniProtKB

positive regulation of myoblast differentiation

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of vasculogenesis

Non-traceable author statement PubMed 17636018. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter in response to hypoxia

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.11. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

perinuclear region of cytoplasm

Inferred from direct assay Ref.16. Source: UniProtKB

   Molecular_functionNF-kappaB binding

Inferred from physical interaction Ref.12. Source: UniProtKB

Notch binding

Inferred from physical interaction Ref.26Ref.13. Source: UniProtKB

ankyrin repeat binding

Inferred from physical interaction Ref.12PubMed 17636018Ref.32Ref.31. Source: UniProtKB

carboxylic acid binding

Inferred from direct assay Ref.25. Source: UniProtKB

cofactor binding

Inferred from direct assay Ref.22. Source: UniProtKB

iron ion binding

Inferred from direct assay Ref.22. Source: UniProtKB

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors

Inferred from experiment. Source: Reactome

oxygen sensor activity

Non-traceable author statement Ref.7. Source: UniProtKB

peptidyl-asparagine 3-dioxygenase activity

Inferred from direct assay PubMed 12215170Ref.11. Source: UniProtKB

peptidyl-histidine dioxygenase activity

Inferred from direct assay Ref.31. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.22. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.22. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.14
Chain2 – 349348Hypoxia-inducible factor 1-alpha inhibitor
PRO_0000083974

Regions

Domain142 – 312171JmjC
Region2 – 125124Interaction with VHL
Region181 – 1833Substrate binding
Region201 – 2033Substrate binding
Region238 – 2392Substrate binding

Sites

Metal binding1991Iron; via tele nitrogen; catalytic
Metal binding1991Zinc; via tele nitrogen
Metal binding2011Iron; via tele nitrogen; catalytic
Metal binding2011Zinc; via tele nitrogen
Metal binding2791Iron; via tele nitrogen; catalytic
Metal binding2791Zinc; via tele nitrogen
Binding site14512-oxoglutarate
Binding site1521Substrate
Binding site19612-oxoglutarate
Binding site20512-oxoglutarate
Binding site21412-oxoglutarate
Binding site29412-oxoglutarate
Binding site3001Substrate; via amide nitrogen
Binding site3211Substrate
Site3401Important for dimer formation

Amino acid modifications

Modified residue21N-acetylalanine Ref.14 Ref.19 Ref.20

Natural variations

Natural variant411P → A. Ref.4
Corresponds to variant rs2295778 [ dbSNP | Ensembl ].
VAR_051028

Experimental info

Mutagenesis1991H → A: Prevents suppression of HIF CAD activity. Strongly stimulates 2-oxoglutarate turnover. No stimulation of 2-oxoglutarate turnover; when associated with R-340. Ref.7
Mutagenesis2011D → A: Prevents suppression of HIF CAD activity. Ref.7 Ref.27 Ref.32
Mutagenesis2011D → E: Loss of HIF1A Asn hydroxylation activity. Slightly stimulates 2-oxoglutarate turnover. Ref.7 Ref.27 Ref.32
Mutagenesis2011D → G: No impact on HIF1A Asn hydroxylation activity. Loss of Asp hydroxylation ability. Strongly stimulates 2-oxoglutarate turnover. Loss of HIF1A Asn hydroxylation activity and slight stimulation of 2-oxoglutarate turnover; when associated with R-296. Ref.7 Ref.27 Ref.32
Mutagenesis2391Q → H: No effect on Asp hydroxylation ability. Ref.32
Mutagenesis2961W → R: Loss of HIF1A Asn hydroxylation activity and slight stimulation of 2-oxoglutarate turnover; when associated with G-201. Ref.27
Mutagenesis3401L → R: Impairs dimer formation, leading to loss of HIF1A Asn hydroxylation activity. No stimulation of 2-oxoglutarate turnover; when associated with A-201. Ref.9 Ref.27
Mutagenesis3441I → R: No effect on dimer formation and HIF1A Asn hydroxylation activity. Ref.9
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 [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Signet-ring cell carcinoma.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-41.
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Muscle.
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-349.
Tissue: Melanoma.
[7]"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] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF HIS-199 AND ASP-201.
[8]"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] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION.
[9]"Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity."
Lancaster D.E., McNeill L.A., McDonough M.A., Aplin R.T., Hewitson K.S., Pugh C.W., Ratcliffe P.J., Schofield C.J.
Biochem. J. 383:429-437(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DIMERIZATION, MASS SPECTROMETRY, MUTAGENESIS OF LEU-340 AND ILE-344.
[10]"Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases."
Koivunen P., Hirsila M., Gunzler V., Kivirikko K.I., Myllyharju J.
J. Biol. Chem. 279:9899-9904(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
[11]"Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor."
Linke S., Stojkoski C., Kewley R.J., Booker G.W., Whitelaw M.L., Peet D.J.
J. Biol. Chem. 279:14391-14397(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[12]"Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)."
Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., McDonough M.A., Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., Pugh C.W., Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J.
Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NFKB1 AND NFKBIA.
[13]"Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways."
Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P., Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J., Lendahl U., Poellinger L.
Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"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] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[15]"MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH)."
Webb J.D., Muranyi A., Pugh C.W., Ratcliffe P.J., Coleman M.L.
Biochem. J. 420:327-333(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PPP1R12A.
[16]"Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1."
Sakamoto T., Seiki M.
J. Biol. Chem. 284:30350-30359(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APBA3, SUBCELLULAR LOCATION.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes."
Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M., Harper J.W., Howley P.M.
Mol. Cell. Biol. 32:3095-3106(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE3A.
[19]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH IRON AND 2-OXOGLUTARATE, SUBUNIT.
[22]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH 786-826 OF HIF1A; IRON; ZINC AND 2-OXOGLUTARATE.
[23]"Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau."
Lee C., Kim S.J., Jeong D.G., Lee S.M., Ryu S.E.
J. Biol. Chem. 278:7558-7563(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), SUBUNIT.
[24]"Selective inhibition of factor inhibiting hypoxia-inducible factor."
McDonough M.A., McNeill L.A., Tilliet M., Papamicael C.A., Chen Q.Y., Banerji B., Hewitson K.S., Schofield C.J.
J. Am. Chem. Soc. 127:7680-7681(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH IRON AND INHIBITOR.
[25]"Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates."
Hewitson K.S., Lienard B.M., McDonough M.A., Clifton I.J., Butler D., Soares A.S., Oldham N.J., McNeill L.A., Schofield C.J.
J. Biol. Chem. 282:3293-3301(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH IRON; SUCCINATE AND FUMARATE.
[26]"Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor."
Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J., Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M., Oldham N.J., Ratcliffe P.J., Schofield C.J.
J. Biol. Chem. 282:24027-24038(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEXES WITH 1930-1949 OR 1997-2016 OF MOUSE NOTCH1; IRON AND 2-OXOGLUTARATE, FUNCTION, SUBUNIT.
[27]"Evidence that two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH)."
Hewitson K.S., Holmes S.L., Ehrismann D., Hardy A.P., Chowdhury R., Schofield C.J., McDonough M.A.
J. Biol. Chem. 283:25971-25978(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 11-349 OF MUTANTS ALA-201 AND GLY-201 IN COMPLEXES WITH 786-826 OR 788-806 OF HIF1A; IRON OR ZINC AND 2-OXOGLUTARATE, MUTAGENESIS OF ASP-201; TRP-296 AND LEU-340.
[28]"Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor."
Conejo-Garcia A., McDonough M.A., Loenarz C., McNeill L.A., Hewitson K.S., Ge W., Lienard B.M., Schofield C.J., Clifton I.J.
Bioorg. Med. Chem. Lett. 20:6125-6128(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) IN COMPLEX WITH IRON AND 2-OXOGLUTARATE ANALOGS.
[29]"Crystal structures of human FIH-1 in complex with quinol family inhibitors."
Moon H., Han S., Park H., Choe J.
Mol. Cells 29:471-474(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 15-349 IN COMPLEX WITH IRON AND QUINOL FAMILY INHIBITORS.
[30]"The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases."
Chowdhury R., Yeoh K.K., Tian Y.M., Hillringhaus L., Bagg E.A., Rose N.R., Leung I.K., Li X.S., Woon E.C., Yang M., McDonough M.A., King O.N., Clifton I.J., Klose R.J., Claridge T.D., Ratcliffe P.J., Schofield C.J., Kawamura A.
EMBO Rep. 12:463-469(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH IRON AND INHIBITORS.
[31]"Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains."
Yang M., Chowdhury R., Ge W., Hamed R.B., McDonough M.A., Claridge T.D., Kessler B.M., Cockman M.E., Ratcliffe P.J., Schofield C.J.
FEBS J. 278:1086-1097(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) IN COMPLEX WITH IRON; 2-OXOGLUTARATE AND 538-558 OF TNKS2, FUNCTION.
[32]"Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor."
Yang M., Ge W., Chowdhury R., Claridge T.D., Kramer H.B., Schmierer B., McDonough M.A., Gong L., Kessler B.M., Ratcliffe P.J., Coleman M.L., Schofield C.J.
J. Biol. Chem. 286:7648-7660(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT HIS-239 IN COMPLEX WITH ZINC; N-OXALYLGLYCINE AND PEPTIDE SUBSTRATE, FUNCTION, INTERACTION WITH ANK1, MUTAGENESIS OF ASP-201 AND GLN-239.
+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.
CH471066 Genomic DNA. Translation: EAW49817.1.
CH471066 Genomic DNA. Translation: EAW49818.1.
BC007719 mRNA. Translation: AAH07719.1.
AL359615 mRNA. Translation: CAB94885.1.
PIRT50633.
RefSeqNP_060372.2. NM_017902.2.
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[»]
2WA3X-ray2.50A1-349[»]
2WA4X-ray2.50A1-349[»]
2XUMX-ray2.20A1-349[»]
2Y0IX-ray2.28A1-349[»]
2YC0X-ray2.15A1-349[»]
2YDEX-ray2.28A1-349[»]
3D8CX-ray2.10A11-349[»]
3KCXX-ray2.60A15-349[»]
3KCYX-ray2.59A15-349[»]
3OD4X-ray2.20A1-349[»]
3P3NX-ray2.40A1-349[»]
3P3PX-ray2.60A1-349[»]
4AI8X-ray2.40A1-349[»]
4B7EX-ray2.50A1-349[»]
4B7KX-ray2.39A1-349[»]
4BIOX-ray2.45A1-349[»]
4JAAX-ray2.39A1-349[»]
ProteinModelPortalQ9NWT6.
SMRQ9NWT6. Positions 9-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120794. 20 interactions.
IntActQ9NWT6. 9 interactions.
MINTMINT-1465958.
STRING9606.ENSP00000299163.

Chemistry

BindingDBQ9NWT6.
ChEMBLCHEMBL5909.

PTM databases

PhosphoSiteQ9NWT6.

Polymorphism databases

DMDM32129605.

Proteomic databases

PaxDbQ9NWT6.
PRIDEQ9NWT6.

Protocols and materials databases

DNASU55662.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299163; ENSP00000299163; ENSG00000166135.
GeneID55662.
KEGGhsa:55662.
UCSCuc001krj.4. human.

Organism-specific databases

CTD55662.
GeneCardsGC10P102285.
HGNCHGNC:17113. HIF1AN.
HPAHPA048742.
MIM606615. gene.
neXtProtNX_Q9NWT6.
PharmGKBPA29284.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71927.
HOGENOMHOG000008146.
HOVERGENHBG051903.
InParanoidQ9NWT6.
KOK18055.
OMAMIKGRYD.
PhylomeDBQ9NWT6.
TreeFamTF329609.

Enzyme and pathway databases

BioCycMetaCyc:HS15407-MONOMER.
ReactomeREACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpressQ9NWT6.
BgeeQ9NWT6.
CleanExHS_HIF1AN.
GenevestigatorQ9NWT6.

Family and domain databases

Gene3D1.10.287.1010. 1 hit.
InterProIPR027452. FIH-1_domII.
IPR003347. JmjC_dom.
[Graphical view]
SMARTSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9NWT6.
GeneWikiHIF1AN.
GenomeRNAi55662.
NextBio60403.
PROQ9NWT6.
SOURCESearch...

Entry information

Entry nameHIF1N_HUMAN
AccessionPrimary (citable) accession number: Q9NWT6
Secondary accession number(s): D3DR69 expand/collapse secondary AC list , Q5W147, Q969Q7, Q9NPV5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

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