Functional domain structures of HIF isoforms and their potential
function. Columns represent different function domains. The hydroxylation sites
are shown above the domain. HIF isoforms are bHLH–PAS proteins, they all
have a bHLH motif, two PAS domains (PAS-A and PAS-B) for the heterodimerization
between HIF-α and HIF-1β. Unlike HIF-1β, HIF-α
subunits have an ODDD that mediates hydroxylation of two proline (P) residues
and the acetylation of a lysine (K) followed by proteasomal degradation, a N-TAD
within the ODDD and a C-TAD, which involved in transcriptional activation. The
proline residues are conserved in HIF-1/2α subunits. Multiple
HIF-3α splice variants exist, such as HIF-3α variant 1 without
C-TAD and HIF-3α variant 2 with a LZIP, which mediates DNA binding and
protein-protein interaction.