HIF1A Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. A higher level expression seen in pituitary tumors as compared to the pituitary gland. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Autophagy; DNA-binding; Transcription factor
Chromosomal Location of human Ortholog: 14q23.2
Cellular Component:  axon cytoplasm; cytoplasm; cytosol; motile cilium; nuclear body; nuclear chromatin; nuclear speck; nucleoplasm; nucleus; protein-containing complex; RNA polymerase II transcription factor complex; transcription factor complex
Molecular Function:  DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; DNA-binding transcription factor activity, RNA polymerase II-specific; E-box binding; enzyme binding; histone acetyltransferase binding; histone deacetylase binding; Hsp90 protein binding; nuclear hormone receptor binding; p53 binding; protein binding; protein domain specific binding; protein heterodimerization activity; protein kinase binding; RNA polymerase II regulatory region sequence-specific DNA binding; transcription factor binding; ubiquitin protein ligase binding
Biological Process:  angiogenesis; axonal transport of mitochondrion; B-1 B cell homeostasis; cardiac ventricle morphogenesis; cartilage development; cellular iron ion homeostasis; cellular response to hypoxia; cellular response to interleukin-1; cerebral cortex development; collagen metabolic process; connective tissue replacement involved in inflammatory response wound healing; cytokine-mediated signaling pathway; digestive tract morphogenesis; dopaminergic neuron differentiation; elastin metabolic process; embryonic hemopoiesis; embryonic placenta development; epithelial cell differentiation involved in mammary gland alveolus development; epithelial to mesenchymal transition; glucose homeostasis; heart looping; hemoglobin biosynthetic process; hypoxia-inducible factor-1alpha signaling pathway; intestinal epithelial cell maturation; iris morphogenesis; lactate metabolic process; lactation; mRNA transcription by RNA polymerase II; muscle cell cellular homeostasis; negative regulation of bone mineralization; negative regulation of gene expression; negative regulation of growth; negative regulation of mesenchymal cell apoptotic process; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; negative regulation of reactive oxygen species metabolic process; negative regulation of thymocyte apoptotic process; negative regulation of TOR signaling; neural crest cell migration; neural fold elevation formation; outflow tract morphogenesis; oxygen homeostasis; positive regulation of angiogenesis; positive regulation of autophagy of mitochondrion; positive regulation of blood vessel endothelial cell migration; positive regulation of chemokine production; positive regulation of chemokine-mediated signaling pathway; positive regulation of endothelial cell proliferation; positive regulation of epithelial cell migration; positive regulation of erythrocyte differentiation; positive regulation of gene expression; positive regulation of glycolytic process; positive regulation of hormone biosynthetic process; positive regulation of insulin secretion involved in cellular response to glucose stimulus; positive regulation of macroautophagy; positive regulation of neuroblast proliferation; positive regulation of nitric-oxide synthase activity; positive regulation of pri-miRNA transcription by RNA polymerase II; positive regulation of receptor biosynthetic process; positive regulation of transcription by RNA polymerase II; positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; positive regulation of transcription, DNA-templated; positive regulation of vascular endothelial growth factor production; positive regulation of vascular endothelial growth factor receptor signaling pathway; post-translational protein modification; protein deubiquitination; protein ubiquitination; regulation of aerobic respiration; regulation of gene expression; regulation of transcription from RNA polymerase II promoter in response to hypoxia; regulation of transcription from RNA polymerase II promoter in response to oxidative stress; regulation of transcription, DNA-templated; regulation of transforming growth factor beta2 production; response to hypoxia; response to iron ion; response to muscle activity; retina vasculature development in camera-type eye; signal transduction; transcription by RNA polymerase II; vascular endothelial growth factor production; visual learning
Reference #:  Q16665 (UniProtKB)
Alt. Names/Synonyms: ARNT interacting protein; ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; BHLHE78; Class E basic helix-loop-helix protein 78; HIF-1-alpha; HIF-1A; HIF-1alpha; HIF1; HIF1-alpha; HIF1A; hypoxia inducible factor 1 alpha subunit; hypoxia inducible factor 1 subunit alpha; hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor); hypoxia-inducible factor 1 alpha isoform I.3; hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor); Hypoxia-inducible factor 1-alpha; hypoxia-inducible factor1alpha; Member of PAS protein 1; member of PAS superfamily 1; MOP1; PAS domain-containing protein 8; PASD8
Gene Symbols: HIF1A
Molecular weight: 92,670 Da
Basal Isoelectric point: 5.17  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  mTOR Signaling  |  Warburg Effect
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  InnateDB  |  Ensembl Protein