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Showing Protein Hypoxia-inducible factor 1-alpha inhibitor (HMDBP01023)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 6 metabolites
Identification
HMDB Protein ID HMDBP01023
Secondary Accession Numbers
  • 6311
Name Hypoxia-inducible factor 1-alpha inhibitor
Synonyms
  1. FIH-1
  2. Factor inhibiting HIF-1
  3. Hypoxia-inducible factor asparagine hydroxylase
Gene Name HIF1AN
Protein Type Unknown
Biological Properties
General Function Involved in metal ion binding
Specific 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.
Pathways
  • Glutaminolysis and Cancer
Reactions
Hypoxia-inducible factor-L-asparagine + Oxoglutaric acid + Oxygen → hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + Succinic acid + CO(2) details
Ankyrin-repeat-L-histidine + Oxoglutaric acid + Oxygen → ankyrin-repeat-(3S)-3-hydroxy-L-histidine + Succinic acid + CO(2) details
GO Classification
Biological Process
peptidyl-aspartic acid hydroxylation
negative regulation of Notch signaling pathway
negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
peptidyl-asparagine hydroxylation
peptidyl-histidine hydroxylation
positive regulation of myoblast differentiation
positive regulation of vasculogenesis
transcription, DNA-dependent
Cellular Component
cytosol
perinuclear region of cytoplasm
nucleus
Molecular Function
oxygen sensor activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
cofactor binding
iron ion binding
carboxylic acid binding
zinc ion binding
protein homodimerization activity
peptidyl-asparagine 3-dioxygenase activity
peptidyl-histidine dioxygenase activity
Cellular Location
  1. Nucleus (Potential)
Gene Properties
Chromosome Location 10
Locus 10q24
SNPs HIF1AN
Gene Sequence 
>1050 bp
ATGGCGGCGACAGCGGCGGAGGCTGTGGCCTCTGGCTCTGGAGAGCCCCGGGAGGAGGCT
GGAGCCCTCGGCCCCGCCTGGGATGAATCCCAGTTGCGCAGTTATAGCTTCCCGACTAGG
CCCATTCCGCGTCTGAGTCAGAGCGACCCCCGGGCAGAGGAGCTTATTGAGAATGAGGAG
CCTGTGGTGCTGACCGACACAAATCTTGTGTATCCTGCCCTGAAATGGGACCTTGAATAC
CTGCAAGAGAATATTGGCAATGGAGACTTCTCTGTGTACAGTGCCAGCACCCACAAGTTC
TTGTACTATGATGAGAAGAAGATGGCCAATTTCCAGAACTTTAAGCCGAGGTCCAACAGG
GAAGAAATGAAATTTCATGAGTTCGTTGAGAAACTGCAGGATATACAGCAGCGAGGAGGG
GAAGAGAGGTTGTATCTGCAGCAAACGCTCAATGACACTGTGGGCAGGAAGATTGTCATG
GACTTCTTAGGTTTTAACTGGAACTGGATTAATAAGCAACAGGGAAAGCGTGGCTGGGGG
CAGCTTACCTCTAACCTGCTGCTCATTGGCATGGAAGGAAATGTGACACCTGCTCACTAT
GATGAGCAGCAGAACTTTTTTGCTCAGATAAAAGGTTACAAACGATGCATCTTATTCCCT
CCGGATCAGTTCGAGTGCCTCTACCCATACCCTGTTCATCACCCATGTGACAGACAGAGC
CAGGTGGACTTTGACAATCCCGACTACGAGAGGTTCCCTAATTTCCAAAATGTGGTTGGT
TACGAAACAGTGGTTGGCCCTGGTGATGTTCTTTACATCCCAATGTACTGGTGGCATCAC
ATAGAGTCATTACTAAATGGGGGGATTACCATCACTGTGAACTTCTGGTATAAGGGGGCT
CCCACCCCTAAGAGAATTGAATATCCTCTCAAAGCTCATCAGAAAGTGGCCATAATGAGA
AACATTGAGAAGATGCTTGGAGAGGCCTTGGGGAACCCACAAGAGGTGGGGCCCTTGTTG
AACACAATGATCAAGGGCCGATACAACTAG
Protein Properties
Number of Residues 349
Molecular Weight 40285.25
Theoretical pI 5.57
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence 
>Hypoxia-inducible factor 1-alpha inhibitor
MAATAAEAVASGSGEPREEAGALGPAWDESQLRSYSFPTRPIPRLSQSDPRAEELIENEE
PVVLTDTNLVYPALKWDLEYLQENIGNGDFSVYSASTHKFLYYDEKKMANFQNFKPRSNR
EEMKFHEFVEKLQDIQQRGGEERLYLQQTLNDTVGRKIVMDFLGFNWNWINKQQGKRGWG
QLTSNLLLIGMEGNVTPAHYDEQQNFFAQIKGYKRCILFPPDQFECLYPYPVHHPCDRQS
QVDFDNPDYERFPNFQNVVGYETVVGPGDVLYIPMYWWHHIESLLNGGITITVNFWYKGA
PTPKRIEYPLKAHQKVAIMRNIEKMLGEALGNPQEVGPLLNTMIKGRYN
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9NWT6
UniProtKB/Swiss-Prot Entry Name HIF1N_HUMAN
PDB IDs
GenBank Gene ID AF395830
GeneCard ID HIF1AN
GenAtlas ID HIF1AN
HGNC ID HGNC:17113
References
General References
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  3. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
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  6. Mahon PC, Hirota K, Semenza GL: FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 2001 Oct 15;15(20):2675-86. [PubMed:11641274 ]
  7. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK: FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002 Jun 15;16(12):1466-71. [PubMed:12080085 ]
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  9. Dann CE 3rd, Bruick RK, Deisenhofer J: Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15351-6. Epub 2002 Nov 13. [PubMed:12432100 ]
  10. Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ: Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha. J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. [PubMed:12446723 ]