Biomarker: HIF-1α

Histology type: endometrial carcinoma

Country: Norway

Region: Bergen

Followed up time :

Subgroup 1 name : Low

Subgroup 1 number: 158

Subgroup 2 name: High

Subgroup 2 number: 42

Conclusion: We show that high stromal HIF-1α expression predicts reduced survival in EC and is associated with increased tumor metabolism at FDG-PET/CT. Importantly; we demonstrate a correlation between tissue and imaging biomarkers reflecting hypoxia, and also possible treatment targets for selected patients.

Sample type : tissue

Sample method: immunohistochemistry,FDG-PET/CT and derived imaging parameters,Oligonucleotide DNA microarray analyses,Magnetic resonance imaging protocol and derived imaging parameters

Expression pattern : stromal HIF-1α expression

Expression elevation: For epithelial and stromal HIF-1α protein expression, high expression was defined as upper quartile, and low expression as the lower three quartiles, based on the number of events in the quartile groups in a survival analysis.

Funtion Uniprot: Hydroxylates HIF-1 alpha at 'Asn-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

UniProt ID: Q9NWT6

UniProt Link: https://www.uniprot.org/uniprotkb/Q9NWT6/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Recommended name: Hypoxia-inducible factor 1-alpha inhibitor

Gene name from HGNC: HIF1A (bHLHe78, HIF-1alpha, HIF1, MOP1, PASD8)

HPA class: Cancer-related genes Human disease related genes Metabolic proteins Plasma proteins Transcription factors

AlphaFold DB: Q9NWT6

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q9NWT6

HPA link: https://www.proteinatlas.org/ENSG00000100644-HIF1A

Tissue specificity RNA from HPA: Tissue enhanced (bone marrow)

Tissue expression from HPA: Mainly nuclear expression with cases of cytoplasmic expression. Including chromosome alignment expression in a subset of cells in gallbladder.

Single cell type specificity Granulosa cells - Unknown function (mainly)

Immune cell specificity: Immune cell enhanced (eosinophil)

Subcellular summary HPA Located in Nucleoplasm, Nuclear bodies

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000100644-HIF1A/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000100644-HIF1A/pathology/endometrial+cancer

Expression figure legend: Stromal HIF-1α protein expression correlated to 18FDG PET/CT markers

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342519/figure/F2/

Survival figure legend: HIF-1α protein expression is a prognostic marker

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342519/figure/F1/

OMIM: 606615

OMIM link2: https://www.omim.org/entry/606615

HGNC ID: HGNC:4910

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4910