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Q9NWT6

- HIF1N_HUMAN

UniProt

Q9NWT6 - HIF1N_HUMAN

Protein

Hypoxia-inducible factor 1-alpha inhibitor

Gene

HIF1AN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 2 (16 Jun 2003)
      Previous versions | rss
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    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

    Fe2+ ion.

    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

    1. ankyrin repeat binding Source: UniProtKB
    2. carboxylic acid binding Source: UniProtKB
    3. cofactor binding Source: UniProtKB
    4. iron ion binding Source: UniProtKB
    5. NF-kappaB binding Source: UniProtKB
    6. Notch binding Source: UniProtKB
    7. 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
    8. oxygen sensor activity Source: UniProtKB
    9. peptidyl-asparagine 3-dioxygenase activity Source: UniProtKB
    10. peptidyl-histidine dioxygenase activity Source: UniProtKB
    11. protein binding Source: UniProtKB
    12. protein homodimerization activity Source: UniProtKB
    13. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to hypoxia Source: Reactome
    2. negative regulation of Notch signaling pathway Source: UniProtKB
    3. negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
    4. oxidation-reduction process Source: UniProtKB
    5. peptidyl-asparagine hydroxylation Source: UniProtKB
    6. peptidyl-aspartic acid hydroxylation Source: UniProtKB
    7. peptidyl-histidine hydroxylation Source: UniProtKB
    8. positive regulation of myoblast differentiation Source: UniProtKB
    9. positive regulation of vasculogenesis Source: UniProtKB
    10. regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
    11. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS15407-MONOMER.
    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: 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

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. nucleus Source: HPA
    4. perinuclear region of cytoplasm Source: UniProtKB

    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.

    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

    ArrayExpressiQ9NWT6.
    BgeeiQ9NWT6.
    CleanExiHS_HIF1AN.
    GenevestigatoriQ9NWT6.

    Organism-specific databases

    HPAiHPA048742.

    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.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. 25 interactions.
    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 – 98
    Turni20 – 223
    Beta strandi24 – 263
    Helixi29 – 313
    Beta strandi39 – 413
    Helixi50 – 578
    Beta strandi62 – 654
    Helixi71 – 755
    Helixi78 – 847
    Beta strandi85 – 884
    Beta strandi90 – 9910
    Helixi105 – 1073
    Turni108 – 1103
    Beta strandi111 – 1133
    Beta strandi117 – 1237
    Helixi125 – 13814
    Beta strandi143 – 1497
    Beta strandi151 – 1544
    Helixi156 – 1638
    Helixi167 – 17610
    Beta strandi182 – 1843
    Beta strandi186 – 1905
    Beta strandi195 – 1995
    Beta strandi202 – 21211
    Beta strandi214 – 2196
    Helixi221 – 2233
    Helixi224 – 2274
    Turni235 – 2384
    Beta strandi239 – 2424
    Beta strandi244 – 2463
    Turni249 – 2513
    Helixi253 – 2575
    Beta strandi260 – 2656
    Beta strandi270 – 2734
    Beta strandi278 – 2836
    Beta strandi290 – 2989
    Helixi312 – 32918
    Beta strandi330 – 3323
    Helixi333 – 3353
    Helixi336 – 3449
    Turni345 – 3473

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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[»]
    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.
    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

    MAATAAEAVA SGSGEPREEA GALGPAWDES QLRSYSFPTR PIPRLSQSDP    50
    RAEELIENEE PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF 100
    LYYDEKKMAN FQNFKPRSNR EEMKFHEFVE KLQDIQQRGG EERLYLQQTL 150
    NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG QLTSNLLLIG MEGNVTPAHY 200
    DEQQNFFAQI KGYKRCILFP PDQFECLYPY PVHHPCDRQS QVDFDNPDYE 250
    RFPNFQNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA 300
    PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN 349
    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:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi32129605.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS7498.1.
    PIRi T50633.
    RefSeqi NP_060372.2. NM_017902.2.
    UniGenei Hs.500788.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1H2K X-ray 2.15 A 1-349 [» ]
    1H2L X-ray 2.25 A 1-349 [» ]
    1H2M X-ray 2.50 A 1-349 [» ]
    1H2N X-ray 2.84 A 1-349 [» ]
    1IZ3 X-ray 2.80 A 1-349 [» ]
    1MZE X-ray 2.20 A 1-349 [» ]
    1MZF X-ray 2.40 A 1-349 [» ]
    1YCI X-ray 2.70 A 1-349 [» ]
    2CGN X-ray 2.40 A 1-349 [» ]
    2CGO X-ray 2.30 A 1-349 [» ]
    2ILM X-ray 2.30 A 1-349 [» ]
    2W0X X-ray 2.12 A 1-349 [» ]
    2WA3 X-ray 2.50 A 1-349 [» ]
    2WA4 X-ray 2.50 A 1-349 [» ]
    2XUM X-ray 2.20 A 1-349 [» ]
    2Y0I X-ray 2.28 A 1-349 [» ]
    2YC0 X-ray 2.15 A 1-349 [» ]
    2YDE X-ray 2.28 A 1-349 [» ]
    3D8C X-ray 2.10 A 11-349 [» ]
    3KCX X-ray 2.60 A 15-349 [» ]
    3KCY X-ray 2.59 A 15-349 [» ]
    3OD4 X-ray 2.20 A 1-349 [» ]
    3P3N X-ray 2.40 A 1-349 [» ]
    3P3P X-ray 2.60 A 1-349 [» ]
    4AI8 X-ray 2.40 A 1-349 [» ]
    4B7E X-ray 2.50 A 1-349 [» ]
    4B7K X-ray 2.39 A 1-349 [» ]
    4BIO X-ray 2.45 A 1-349 [» ]
    4JAA X-ray 2.39 A 1-349 [» ]
    ProteinModelPortali Q9NWT6.
    SMRi Q9NWT6. Positions 9-349.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120794. 25 interactions.
    IntActi Q9NWT6. 9 interactions.
    MINTi MINT-1465958.
    STRINGi 9606.ENSP00000299163.

    Chemistry

    BindingDBi Q9NWT6.
    ChEMBLi CHEMBL5909.

    PTM databases

    PhosphoSitei Q9NWT6.

    Polymorphism databases

    DMDMi 32129605.

    Proteomic databases

    MaxQBi Q9NWT6.
    PaxDbi Q9NWT6.
    PRIDEi Q9NWT6.

    Protocols and materials databases

    DNASUi 55662.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000299163 ; ENSP00000299163 ; ENSG00000166135 .
    GeneIDi 55662.
    KEGGi hsa:55662.
    UCSCi uc001krj.4. human.

    Organism-specific databases

    CTDi 55662.
    GeneCardsi GC10P102285.
    HGNCi HGNC:17113. HIF1AN.
    HPAi HPA048742.
    MIMi 606615. gene.
    neXtProti NX_Q9NWT6.
    PharmGKBi PA29284.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG71927.
    HOGENOMi HOG000008146.
    HOVERGENi HBG051903.
    InParanoidi Q9NWT6.
    KOi K18055.
    OMAi MIKGRYD.
    PhylomeDBi Q9NWT6.
    TreeFami TF329609.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS15407-MONOMER.
    Reactomei REACT_121226. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.

    Miscellaneous databases

    EvolutionaryTracei Q9NWT6.
    GeneWikii HIF1AN.
    GenomeRNAii 55662.
    NextBioi 60403.
    PROi Q9NWT6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9NWT6.
    Bgeei Q9NWT6.
    CleanExi HS_HIF1AN.
    Genevestigatori Q9NWT6.

    Family and domain databases

    Gene3Di 1.10.287.1010. 1 hit.
    InterProi IPR027445. FIH-1.
    IPR027452. FIH-1_domII.
    IPR003347. JmjC_dom.
    [Graphical view ]
    PANTHERi PTHR12461:SF19. PTHR12461:SF19. 1 hit.
    SMARTi SM00558. JmjC. 1 hit.
    [Graphical view ]
    PROSITEi PS51184. JMJC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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].
    20. 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. 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: October 1, 2014
    This is version 131 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

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