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. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB 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. Interacts with the HIF1A beta/ARNT subunit; heterodimerization is required for DNA binding. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability. Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with TSGA10. Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia- mimicking conditions. Interacts with USP20. Interacts with RACK1; promotes HIF1A ubiquitination and proteasome- mediated degradation. Interacts (via N-terminus) with USP19. Under reduced oxygen tension. Induced also by various receptor-mediated factors such as growth factors, cytokines, and circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, TNF, IL1B, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2 and LIMD1. 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. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Transcription factor; DNA-binding; Autophagy
Molecular Function: enzyme binding; histone acetyltransferase binding; histone deacetylase binding; Hsp90 protein binding; nuclear hormone receptor binding; protein binding; protein complex binding; protein heterodimerization activity; protein kinase binding; RNA polymerase II transcription factor activity, enhancer binding; sequence-specific DNA binding; transcription factor activity; transcription factor binding; ubiquitin protein ligase binding
Biological Process: acute-phase response; angiogenesis; axon transport of mitochondrion; B-1 B cell homeostasis; cartilage development; cellular iron ion homeostasis; cellular response to insulin stimulus; cerebral cortex development; collagen metabolic process; connective tissue replacement during inflammatory response; digestive tract morphogenesis; elastin metabolic process; embryonic hemopoiesis; embryonic placenta development; epithelial to mesenchymal transition; heart looping; hemoglobin biosynthetic process; lactate metabolic process; lactation; maternal process involved in pregnancy; mRNA transcription from RNA polymerase II promoter; muscle maintenance; negative regulation of bone mineralization; negative regulation of growth; negative regulation of TOR signaling pathway; negative regulation of transcription from RNA polymerase II promoter; negative regulation of vasoconstriction; neural crest cell migration; neural fold elevation formation; oxygen homeostasis; positive regulation of angiogenesis; positive regulation of apoptosis; positive regulation of cell size; positive regulation of chemokine production; positive regulation of endothelial cell proliferation; positive regulation of erythrocyte differentiation; positive regulation of glycolysis; positive regulation of hormone biosynthetic process; positive regulation of neuroblast proliferation; positive regulation of nitric-oxide synthase activity; positive regulation of smooth muscle cell proliferation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; positive regulation of vascular endothelial growth factor receptor signaling pathway; regulation of gene expression; regulation of transcription from RNA polymerase II promoter in response to oxidative stress; regulation of transcription, DNA-dependent; regulation of transforming growth factor-beta2 production; response to alkaloid; response to estradiol stimulus; response to glucocorticoid stimulus; response to hypoxia; response to muscle activity; response to purine; response to salt stress; response to X-ray; signal transduction; transcription from RNA polymerase II promoter; visual learning
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.