ID:HIF1N_HUMAN DESCRIPTION: RecName: Full=Hypoxia-inducible factor 1-alpha inhibitor; EC=1.14.11.30; EC=1.14.11.n4; AltName: Full=Factor inhibiting HIF-1; Short=FIH-1; AltName: Full=Hypoxia-inducible factor asparagine hydroxylase; 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. CATALYTIC ACTIVITY: Hypoxia-inducible factor-L-asparagine + 2- oxoglutarate + O(2) = hypoxia-inducible factor-(3S)-3-hydroxy-L- asparagine + succinate + CO(2). CATALYTIC ACTIVITY: Ankyrin-repeat-L-histidine + 2-oxoglutarate + O(2) = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CO(2). COFACTOR: Fe(2+) ion. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=100 uM for HIF1A (788-822) peptide; KM=160 uM for HIF2A (832-866) peptide; KM=0.5 uM for Fe(2+); KM=25 uM for 2-oxoglutarate; KM=260 uM for ascorbate; KM=90 uM for O(2); Note=The kinetic constants are determined for the recombinant FLAG-His-tagged protein; SUBUNIT: 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. INTERACTION: Q96DX5:ASB9; NbExp=3; IntAct=EBI-745632, EBI-745641; Q16665:HIF1A; NbExp=3; IntAct=EBI-745632, EBI-447269; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Note=Mainly cytoplasmic localization, but interaction with NOTCH1 results in nuclear localization and interaction with ABPA3 results in perinuclear localization in macrophages. MASS SPECTROMETRY: Mass=40566; Method=Electrospray; Range=1-349; Source=PubMed:15239670; SIMILARITY: Contains 1 JmjC domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NWT6
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005112 Notch binding GO:0005506 iron ion binding GO:0005515 protein binding GO:0008270 zinc ion binding GO:0016491 oxidoreductase activity GO:0016706 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 GO:0019826 oxygen sensor activity GO:0031406 carboxylic acid binding GO:0036139 peptidyl-histidine dioxygenase activity GO:0036140 peptidyl-asparagine 3-dioxygenase activity GO:0042803 protein homodimerization activity GO:0046872 metal ion binding GO:0048037 cofactor binding GO:0051059 NF-kappaB binding GO:0051213 dioxygenase activity GO:0071532 ankyrin repeat binding
Biological Process: GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0036138 peptidyl-histidine hydroxylation GO:0042264 peptidyl-aspartic acid hydroxylation GO:0042265 peptidyl-asparagine hydroxylation GO:0045663 positive regulation of myoblast differentiation GO:0045746 negative regulation of Notch signaling pathway GO:0055114 oxidation-reduction process GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061428 negative regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:2001214 positive regulation of vasculogenesis
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
