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 (By similarity). 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 (By similarity). Induced by reactive oxygen species (ROS). Interacts with the ARNT; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability (By similarity). 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, APEX1 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 (By similarity). Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription (By similarity). Interacts (via the ODD domain) with NAA10; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation (By similarity). Interacts with TSGA10. Interacts with HIF3A (By similarity). 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. Interacts with SIRT2. Interacts (deacetylated form) with EGLN1. Interacts with CBFA2T3. Interacts with HSP90AA1 and HSP90AB1. Interacts with DCUN1D1; this interaction increases the interaction between VHL and DCUN1D1. Interacts with HIF1AN (By similarity). Colocalizes with HIF3A in the nucleus and speckles. Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID) (By similarity). S-nitrosylation of Cys-793 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex. Acetylation of Lys-533 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation. Deacetylation of Lys-702 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation (By similarity). Requires phosphorylation for DNA-binding. Phosphorylation at Ser-248 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding. Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome (By similarity). The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Both sumoylation and desumoylation seem to be involved in the regulation of its stability during hypoxia. Sumoylation can promote either its stabilization or its VHL-dependent degradation by promoting hydroxyproline-independent HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination and proteasomal degradation. Desumoylation by SENP1 increases its stability amd transcriptional activity. There is a disaccord between various publications on the effect of sumoylation and desumoylation on its stability and transcriptional activity (By similarity). In normoxia, is hydroxylated on Pro-403 and Pro-565 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-565. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). In normoxia, is hydroxylated on Asn-796 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Repressed by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated hydroxylation and subsequent proteasomal degradation.