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Protein

Hypoxia-inducible factor 1-alpha inhibitor

Gene

HIF1AN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.8 Publications

Catalytic activityi

Hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2.
Ankyrin-repeat-L-histidine + 2-oxoglutarate + O2 = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CO2.

Cofactori

Kineticsi

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

  1. KM=100 µM for HIF1A (788-822) peptide1 Publication
  2. KM=160 µM for HIF2A (832-866) peptide1 Publication
  3. KM=0.5 µM for Fe2+1 Publication
  4. KM=25 µM for 2-oxoglutarate1 Publication
  5. KM=260 µM for ascorbate1 Publication
  6. KM=90 µM for O21 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei145 – 14512-oxoglutarate3 Publications
    Binding sitei152 – 1521Substrate
    Binding sitei196 – 19612-oxoglutarate3 Publications
    Metal bindingi199 – 1991Iron; via tele nitrogen; catalytic8 Publications
    Metal bindingi201 – 2011Iron; via tele nitrogen; catalytic8 Publications
    Binding sitei205 – 20512-oxoglutarate3 Publications
    Binding sitei214 – 21412-oxoglutarate3 Publications
    Metal bindingi279 – 2791Iron; via tele nitrogen; catalytic8 Publications
    Binding sitei294 – 29412-oxoglutarate3 Publications
    Binding sitei300 – 3001Substrate; via amide nitrogen
    Binding sitei321 – 3211Substrate
    Sitei340 – 3401Important for dimer formation

    GO - Molecular functioni

    • ankyrin repeat binding Source: UniProtKB
    • carboxylic acid binding Source: UniProtKB
    • cofactor binding Source: UniProtKB
    • iron ion binding Source: UniProtKB
    • NF-kappaB binding Source: UniProtKB
    • Notch binding 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 Source: Reactome
    • oxygen sensor activity Source: UniProtKB
    • peptidyl-asparagine 3-dioxygenase activity Source: UniProtKB
    • peptidyl-histidine dioxygenase activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • cellular response to hypoxia Source: Reactome
    • negative regulation of Notch signaling pathway Source: UniProtKB
    • negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    • peptidyl-asparagine hydroxylation Source: UniProtKB
    • peptidyl-aspartic acid hydroxylation Source: UniProtKB
    • peptidyl-histidine hydroxylation Source: UniProtKB
    • positive regulation of myoblast differentiation Source: UniProtKB
    • positive regulation of vasculogenesis Source: UniProtKB
    • regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
    • transcription, DNA-templated Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS15407-MONOMER.
    BRENDAi1.14.11.16. 2681.
    ReactomeiREACT_121226. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:HIF1AN
    Synonyms:FIH1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:17113. HIF1AN.

    Subcellular locationi

    • 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.

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • nucleoplasm Source: HPA
    • perinuclear region of cytoplasm Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi199 – 1991H → A: Prevents suppression of HIF CAD activity. Strongly stimulates 2-oxoglutarate turnover. No stimulation of 2-oxoglutarate turnover; when associated with R-340. 1 Publication
    Mutagenesisi201 – 2011D → A: Prevents suppression of HIF CAD activity. 3 Publications
    Mutagenesisi201 – 2011D → E: Loss of HIF1A Asn hydroxylation activity. Slightly stimulates 2-oxoglutarate turnover. 3 Publications
    Mutagenesisi201 – 2011D → 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. 3 Publications
    Mutagenesisi239 – 2391Q → H: No effect on Asp hydroxylation ability. 1 Publication
    Mutagenesisi296 – 2961W → R: Loss of HIF1A Asn hydroxylation activity and slight stimulation of 2-oxoglutarate turnover; when associated with G-201. 1 Publication
    Mutagenesisi340 – 3401L → R: Impairs dimer formation, leading to loss of HIF1A Asn hydroxylation activity. No stimulation of 2-oxoglutarate turnover; when associated with A-201. 2 Publications
    Mutagenesisi344 – 3441I → R: No effect on dimer formation and HIF1A Asn hydroxylation activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA29284.

    Polymorphism and mutation databases

    BioMutaiHIF1AN.
    DMDMi32129605.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed3 Publications
    Chaini2 – 349348Hypoxia-inducible factor 1-alpha inhibitorPRO_0000083974Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine3 Publications

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ9NWT6.
    PaxDbiQ9NWT6.
    PRIDEiQ9NWT6.

    PTM databases

    PhosphoSiteiQ9NWT6.

    Expressioni

    Gene expression databases

    BgeeiQ9NWT6.
    CleanExiHS_HIF1AN.
    ExpressionAtlasiQ9NWT6. baseline and differential.
    GenevestigatoriQ9NWT6.

    Organism-specific databases

    HPAiCAB069903.
    HPA048742.
    HPA065302.

    Interactioni

    Subunit structurei

    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. Interacts with ANKS3 (By similarity).By similarity17 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ASB9Q96DX53EBI-745632,EBI-745641
    HIF1AQ166654EBI-745632,EBI-447269
    TNKSO952712EBI-745632,EBI-1105254
    TNKS2Q9H2K23EBI-745632,EBI-4398527

    Protein-protein interaction databases

    BioGridi120794. 35 interactions.
    DIPiDIP-35527N.
    IntActiQ9NWT6. 9 interactions.
    MINTiMINT-1465958.
    STRINGi9606.ENSP00000299163.

    Structurei

    Secondary structure

    1
    349
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi2 – 98Combined sources
    Turni20 – 223Combined sources
    Beta strandi24 – 263Combined sources
    Helixi29 – 313Combined sources
    Beta strandi39 – 413Combined sources
    Helixi50 – 578Combined sources
    Beta strandi62 – 654Combined sources
    Helixi71 – 755Combined sources
    Helixi78 – 847Combined sources
    Beta strandi85 – 884Combined sources
    Beta strandi90 – 9910Combined sources
    Helixi105 – 1073Combined sources
    Turni108 – 1103Combined sources
    Beta strandi111 – 1133Combined sources
    Beta strandi117 – 1237Combined sources
    Helixi125 – 13814Combined sources
    Beta strandi143 – 1497Combined sources
    Beta strandi151 – 1544Combined sources
    Helixi156 – 1638Combined sources
    Helixi167 – 17610Combined sources
    Beta strandi182 – 1843Combined sources
    Beta strandi186 – 1905Combined sources
    Beta strandi195 – 1995Combined sources
    Beta strandi202 – 21211Combined sources
    Beta strandi214 – 2196Combined sources
    Helixi221 – 2233Combined sources
    Helixi224 – 2274Combined sources
    Turni235 – 2384Combined sources
    Beta strandi239 – 2424Combined sources
    Beta strandi244 – 2463Combined sources
    Turni249 – 2513Combined sources
    Helixi253 – 2575Combined sources
    Beta strandi260 – 2656Combined sources
    Beta strandi270 – 2734Combined sources
    Beta strandi278 – 2836Combined sources
    Beta strandi290 – 2989Combined sources
    Helixi312 – 32918Combined sources
    Beta strandi330 – 3323Combined sources
    Helixi333 – 3353Combined sources
    Helixi336 – 3449Combined sources
    Turni345 – 3473Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    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[»]
    4NR1X-ray2.68A1-349[»]
    ProteinModelPortaliQ9NWT6.
    SMRiQ9NWT6. Positions 9-349.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NWT6.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini142 – 312171JmjCPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 125124Interaction with VHLAdd
    BLAST
    Regioni181 – 1833Substrate binding
    Regioni201 – 2033Substrate binding
    Regioni238 – 2392Substrate binding

    Sequence similaritiesi

    Contains 1 JmjC domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG71927.
    GeneTreeiENSGT00530000062914.
    HOGENOMiHOG000008146.
    HOVERGENiHBG051903.
    InParanoidiQ9NWT6.
    KOiK18055.
    OMAiMIKGRYD.
    PhylomeDBiQ9NWT6.
    TreeFamiTF329609.

    Family and domain databases

    Gene3Di1.10.287.1010. 1 hit.
    InterProiIPR027445. FIH-1.
    IPR027452. FIH-1_domII.
    IPR003347. JmjC_dom.
    [Graphical view]
    PANTHERiPTHR12461:SF19. PTHR12461:SF19. 1 hit.
    SMARTiSM00558. JmjC. 1 hit.
    [Graphical view]
    PROSITEiPS51184. JMJC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9NWT6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAATAAEAVA SGSGEPREEA GALGPAWDES QLRSYSFPTR PIPRLSQSDP
    60 70 80 90 100
    RAEELIENEE PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF
    110 120 130 140 150
    LYYDEKKMAN FQNFKPRSNR EEMKFHEFVE KLQDIQQRGG EERLYLQQTL
    160 170 180 190 200
    NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG QLTSNLLLIG MEGNVTPAHY
    210 220 230 240 250
    DEQQNFFAQI KGYKRCILFP PDQFECLYPY PVHHPCDRQS QVDFDNPDYE
    260 270 280 290 300
    RFPNFQNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA
    310 320 330 340
    PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN
    Length:349
    Mass (Da):40,285
    Last modified:June 16, 2003 - v2
    Checksum:i96A033BA7B3BD8C7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti10 – 101A → T in BAA91291 (PubMed:14702039).Curated
    Sequence conflicti28 – 281D → H in BAA91291 (PubMed:14702039).Curated
    Sequence conflicti156 – 1561R → G in BAA91291 (PubMed:14702039).Curated

    Mass spectrometryi

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411P → A.1 Publication
    Corresponds to variant rs2295778 [ dbSNP | Ensembl ].
    VAR_051028

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS7498.1.
    PIRiT50633.
    RefSeqiNP_060372.2. NM_017902.2.
    UniGeneiHs.500788.

    Genome annotation databases

    EnsembliENST00000299163; ENSP00000299163; ENSG00000166135.
    GeneIDi55662.
    KEGGihsa:55662.
    UCSCiuc001krj.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS7498.1.
    PIRiT50633.
    RefSeqiNP_060372.2. NM_017902.2.
    UniGeneiHs.500788.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    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[»]
    4NR1X-ray2.68A1-349[»]
    ProteinModelPortaliQ9NWT6.
    SMRiQ9NWT6. Positions 9-349.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi120794. 35 interactions.
    DIPiDIP-35527N.
    IntActiQ9NWT6. 9 interactions.
    MINTiMINT-1465958.
    STRINGi9606.ENSP00000299163.

    Chemistry

    BindingDBiQ9NWT6.
    ChEMBLiCHEMBL5909.

    PTM databases

    PhosphoSiteiQ9NWT6.

    Polymorphism and mutation databases

    BioMutaiHIF1AN.
    DMDMi32129605.

    Proteomic databases

    MaxQBiQ9NWT6.
    PaxDbiQ9NWT6.
    PRIDEiQ9NWT6.

    Protocols and materials databases

    DNASUi55662.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000299163; ENSP00000299163; ENSG00000166135.
    GeneIDi55662.
    KEGGihsa:55662.
    UCSCiuc001krj.4. human.

    Organism-specific databases

    CTDi55662.
    GeneCardsiGC10P102285.
    HGNCiHGNC:17113. HIF1AN.
    HPAiCAB069903.
    HPA048742.
    HPA065302.
    MIMi606615. gene.
    neXtProtiNX_Q9NWT6.
    PharmGKBiPA29284.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG71927.
    GeneTreeiENSGT00530000062914.
    HOGENOMiHOG000008146.
    HOVERGENiHBG051903.
    InParanoidiQ9NWT6.
    KOiK18055.
    OMAiMIKGRYD.
    PhylomeDBiQ9NWT6.
    TreeFamiTF329609.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS15407-MONOMER.
    BRENDAi1.14.11.16. 2681.
    ReactomeiREACT_121226. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.

    Miscellaneous databases

    ChiTaRSiHIF1AN. human.
    EvolutionaryTraceiQ9NWT6.
    GeneWikiiHIF1AN.
    GenomeRNAii55662.
    NextBioi60403.
    PROiQ9NWT6.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9NWT6.
    CleanExiHS_HIF1AN.
    ExpressionAtlasiQ9NWT6. baseline and differential.
    GenevestigatoriQ9NWT6.

    Family and domain databases

    Gene3Di1.10.287.1010. 1 hit.
    InterProiIPR027445. FIH-1.
    IPR027452. FIH-1_domII.
    IPR003347. JmjC_dom.
    [Graphical view]
    PANTHERiPTHR12461:SF19. PTHR12461:SF19. 1 hit.
    SMARTiSM00558. JmjC. 1 hit.
    [Graphical view]
    PROSITEiPS51184. JMJC. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    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.
      , 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.
      , 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. 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. 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. 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], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    20. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [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. 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. 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. 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.

    Entry informationi

    Entry nameiHIF1N_HUMAN
    AccessioniPrimary (citable) accession number: Q9NWT6
    Secondary accession number(s): D3DR69
    , Q5W147, Q969Q7, Q9NPV5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 16, 2003
    Last sequence update: June 16, 2003
    Last modified: April 29, 2015
    This is version 138 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.