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 (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (, ). Activity is enhanced by interaction with NCOA1 and/or NCOA2 . Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (, ). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia .
(Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state . In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons . Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response .
Subcellular locations: Cytoplasm, Nucleus, Nucleus speckle
Colocalizes with HIF3A in the nucleus and speckles (By similarity). Cytoplasmic in normoxia, nuclear translocation in response to 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.