Names & Taxonomy
- Uniprot ID:
- Q9NWT6
- Entry Name:
- HIF1N_HUMAN
- Status:
- reviewed
- Protein Names:
- Hypoxia-inducible factor 1-alpha inhibitor (EC 1.14.11.30) (EC 1.14.11.n4) (Factor inhibiting HIF-1) (FIH-1) (Hypoxia-inducible factor asparagine hydroxylase)
- Gene Names:
- HIF1AN FIH1
- Gene Names Primary:
- HIF1AN
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 349
- Sequence:
- MAATAAEAVASGSGEPREEAGALGPAWDESQLRSYSFPTRPIPRLSQSDPRAEELIENEEPVVLTDTNLVYPALKWDLEYLQENIGNGDFSVYSASTHKFLYYDEKKMANFQNFKPRSNREEMKFHEFVEKLQDIQQRGGEERLYLQQTLNDTVGRKIVMDFLGFNWNWINKQQGKRGWGQLTSNLLLIGMEGNVTPAHYDEQQNFFAQIKGYKRCILFPPDQFECLYPYPVHHPCDRQSQVDFDNPDYERFPNFQNVVGYETVVGPGDVLYIPMYWWHHIESLLNGGITITVNFWYKGAPTPKRIEYPLKAHQKVAIMRNIEKMLGEALGNPQEVGPLLNTMIKGRYN
- Proteomes:
- UP000005640
Subcellular location
- 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.
Function
- 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).; Ankyrin-repeat-L-histidine + 2-oxoglutarate + O(2) = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CO(2).
- Cofactor:
- COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: KM=100 uM for HIF1A (788-822) peptide
- Gene Ontology Go:
- cytoplasm
cytosol
nucleoplasm
perinuclear region of cytoplasm
ankyrin repeat binding
carboxylic acid binding
cofactor binding
iron ion binding
NF-kappaB binding
Notch binding
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
oxygen sensor activity
peptidyl-asparagine 3-dioxygenase activity
peptidyl-histidine dioxygenase activity
protein homodimerization activity
zinc ion binding
cellular response to hypoxia
negative regulation of Notch signaling pathway
negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
oxidation-reduction process
peptidyl-asparagine hydroxylation
peptidyl-aspartic acid hydroxylation
peptidyl-histidine hydroxylation
positive regulation of myoblast differentiation
positive regulation of vasculogenesis
regulation of transcription from RNA polymerase II promoter in response to hypoxia
transcription, DNA-templated - Gene Ontology Biological Process:
- cellular response to hypoxia
negative regulation of Notch signaling pathway
negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
oxidation-reduction process
peptidyl-asparagine hydroxylation
peptidyl-aspartic acid hydroxylation
peptidyl-histidine hydroxylation
positive regulation of myoblast differentiation
positive regulation of vasculogenesis
regulation of transcription from RNA polymerase II promoter in response to hypoxia
transcription, DNA-templated - Gene Ontology Molecular Function:
- ankyrin repeat binding
carboxylic acid binding
cofactor binding
iron ion binding
NF-kappaB binding
Notch binding
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
oxygen sensor activity
peptidyl-asparagine 3-dioxygenase activity
peptidyl-histidine dioxygenase activity
protein homodimerization activity
zinc ion binding - Gene Ontology Cellular Component:
- cytoplasm
cytosol
nucleoplasm
perinuclear region of cytoplasm - Keywords:
- 3D-structure
Acetylation
Complete proteome
Cytoplasm
Dioxygenase
Iron
Metal-binding
Nucleus
Oxidoreductase
Polymorphism
Reference proteome
Transcription
Transcription regulation - Interacts With:
- Q96DX5; Q16665; Q96FW1; O95271; Q9H2K2