HIF1A

Hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
PDB rendering based on 1h2k.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1H2K, 1H2L, 1H2M, 1L3E, 1L8C, 1LM8, 1LQB, 2ILM, 3HQR, 3HQU, 4AJY, 4H6J
Identifiers
Symbols	HIF1A; HIF-1A; HIF-1alpha; HIF1; HIF1-ALPHA; MOP1; PASD8; bHLHe78
External IDs	OMIM: 603348 MGI: 106918 HomoloGene: 1171 ChEMBL: 4261 GeneCards: HIF1A Gene
Gene Ontology Molecular function • protein binding transcription factor activity • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription • sequence-specific DNA binding transcription factor activity • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity • signal transducer activity • protein binding • transcription factor binding • enzyme binding • protein kinase binding • ubiquitin protein ligase binding • histone acetyltransferase binding • histone deacetylase binding • sequence-specific DNA binding • transcription regulatory region DNA binding • protein heterodimerization activity • Hsp90 protein binding Cellular component • nucleus • nucleoplasm • transcription factor complex • nucleolus • cytoplasm • cytosol Biological process • angiogenesis • response to hypoxia • neural crest cell migration • epithelial to mesenchymal transition • embryonic placenta development • B-1 B cell homeostasis • positive regulation of endothelial cell proliferation • heart looping • positive regulation of neuroblast proliferation • connective tissue replacement involved in inflammatory response wound healing • outflow tract morphogenesis • cardiac ventricle morphogenesis • lactate metabolic process • regulation of transcription, DNA-dependent • cellular iron ion homeostasis • signal transduction • Notch signaling pathway • lactation • visual learning • regulation of gene expression • vascular endothelial growth factor production • positive regulation vascular endothelial growth factor production • positive regulation of epithelial cell migration • positive regulation of receptor biosynthetic process • response to muscle activity • axon transport of mitochondrion • neural fold elevation formation • cerebral cortex development • negative regulation of bone mineralization • positive regulation of vascular endothelial growth factor receptor signaling pathway • negative regulation of TOR signaling cascade • oxygen homeostasis • positive regulation of chemokine production • regulation of transforming growth factor beta2 production • collagen metabolic process • cellular response to stress • embryonic hemopoiesis • positive regulation of insulin secretion involved in cellular response to glucose stimulus • hemoglobin biosynthetic process • glucose homeostasis • mRNA transcription from RNA polymerase II promoter • negative regulation of neuron apoptotic process • regulation of transcription from RNA polymerase II promoter in response to oxidative stress • positive regulation of erythrocyte differentiation • positive regulation of angiogenesis • positive regulation of glycolysis • positive regulation of transcription, DNA-dependent • negative regulation of growth • positive regulation of transcription from RNA polymerase II promoter • muscle cell homeostasis • positive regulation of hormone biosynthetic process • digestive tract morphogenesis • positive regulation of nitric-oxide synthase activity • cartilage development • elastin metabolic process • intestinal epithelial cell maturation • epithelial cell differentiation involved in mammary gland alveolus development • retina vasculature development in camera-type eye • regulation of transcription from RNA polymerase II promoter in response to hypoxia • positive regulation of transcription from RNA polymerase II promoter in response to hypoxia • positive regulation of chemokine-mediated signaling pathway • cellular response to interleukin-1 • cellular response to hypoxia • dopaminergic neuron differentiation • negative regulation of mesenchymal cell apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3091	15251
Ensembl	ENSG00000100644	ENSMUSG00000021109
UniProt	Q16665	Q61221
RefSeq (mRNA)	NM_001243084	NM_010431
RefSeq (protein)	NP_001230013	NP_034561
Location (UCSC)	Chr 14: 62.16 – 62.21 Mb	Chr 12: 73.9 – 73.95 Mb
PubMed search
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Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a protein that in humans is encoded by the HIF1A gene.^[1][2] Two alternative transcripts encoding different isoforms have been identified.^[3]

Structure

HIF1 is a heterodimeric basic helix-loop-helix structure^[4] composed of Hif1a, the alpha subunit (this protein), and the aryl hydrocarbon receptor nuclear translocator (Arnt), the beta subunit.

Function

The protein encoded by HIF1 is a bHLH - PAS transcription factor found in mammalian cells growing at low oxygen concentrations. It plays an essential role in cellular and systemic responses to hypoxia.^[5] This is one of the class of hypoxia inducible factors, a family that includes Hif1a, Hif2a, and Hif3a.

Regulation

HIF-1alpha abundance (and its subsequent activity) is regulated transcriptionally in an NF-κB-dependent manner.^[6] In addition, the coordinated activity of the prolyl hydroxylases (PHDs) maintain the appropriate balance of HIF-1α protein in the post-translation phase.^[7]

PHDs rely on iron among other molecules to hydroxylate HIF-1alpha; as such, iron chelators such as DFO have proven successful in HIF-1alpha stabilization.^{[citation needed]} HBO (Hyperbaric oxygen therapy) and HIF-1alpha imitators such as cobalt chloride have also been successfully utilized.^{[citation needed]}

Factors increasing HIF-1α^[8]

• Modulator of Degradation:
  • Oxygen-Dependent:
    • EPF UCP (degrades pHVL)
    • VDU2 (de-ubiquitinates HIF-1α)
    • SUMOylation (via RSUME)
    • DeSUMOylation ( via SENP1)
  • Oxygen-independent:
    • Calcineurin A ( Ca2+-dependent via RACK1)
• Modulators of translation:
  • RNA-binding proteins, PTB, and HuR
  • PtdIns3K and MAPK pathways
  • IRES-mediated translation
  • calcium signaling
  • miRNAs

Factors decreasing HIF-1α^[8]

• Modulator of Degradation:
  • Oxygen-Dependent:
    • PHD, pVHL, OS-9 and SSAT2
    • SUMOylation
  • Oxygen-independent
    • RACK1 and SSAT1
    • GSK3β
    • FOXO4
• Modulators of translation:
  • Calcium signaling
  • miRNAs

Interactions

HIF1A has been shown to interact with pVHL,^[9] PSMA7,^[10] NR4A,^[11] STAT3,^[12] CREBB,^[13][14][15] ARNTL,^[16] ARNT,^[2][17] P53,^{[18][19][20][21]} EP300,^[22][23] HIF1AN,^[24] Mdm2,^[18][19] VH^{[11][12][15][24][25][26][27][28][29][30]} and UBC.^[11][15][30]

Clinical significance

Overexpression of a natural antisense transcript (aHIF) of this gene is associated with nonpapillary renal carcinomas.^[31]

See also

• Hypoxia inducible factors

References

Further reading

v t e PDB gallery 1h2k: FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH HIF-1 ALPHA FRAGMENT PEPTIDE  1h2l: FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH HIF-1 ALPHA FRAGMENT PEPTIDE  1h2m: FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH HIF-1 ALPHA FRAGMENT PEPTIDE  1l3e: NMR Structures of the HIF-1alpha CTAD/p300 CH1 Complex  1l8c: STRUCTURAL BASIS FOR HIF-1ALPHA/CBP RECOGNITION IN THE CELLULAR HYPOXIC RESPONSE  1lqb: Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex