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HIF-α subunit includes HIF-1α, HIF-2α (also called EPAS1) ⁴ and HIF-3α ⁵. Compared to HIF-1α, HIF-2α and HIF-3α show biochemical similarities such as heterodimerisation with HIF-1β but their functions are not well understood.

HIF subunits have more or less the same structure (see figure) belonging to the basic Helix-Loop-Helix (bHLH)- PAS family (PAS is an acronym for the first recognised protein Per, ARNT and Sim). The bHLH domain is essential for DNA binding activity and the PAS domain is useful for heterodimerisation. The presence of two Transcriptional Activation Domain (TAD) is functionality important for the recruitment of p300 and CREB proteins implicated in transcription. HIF-3α is the only subunit of the family which induces a negative regulation of the HIF pathway ⁶.

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