Regulation of Gene Expression by the Hypoxia-Inducible Factors

Schematic representation of human HIF-1a, HIF-2 a, and ARNT. HIF-1α, HIF-2α, and ARNT are basic-Helix-Loop-Helix–Per-ARNT-Sim (bHLH–PAS) proteins that contain an N-terminal bHLH domain and two PAS domains. HIF-1α and HIF-2α also contain an oxygen-dependent degradation domain (ODD) that mediates oxygen-regulated stability, and a C-terminal transactivation domain (CAD) whose transcriptional repression in normoxia is controlled by the inhibitory domain (ID). ARNT has a transactivation domain (TAD) that serves no function in the context of HIF-α activity. Amino acid numbers for each domain are indicated.