P3373A

Rabbit Anti-PHD1-3, pan (HIF-prolyl Hydroxylase 1-3)

Oxygen is absolutely critical for the survival of mammalian cells. Hypoxia induced factor (HIF) is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. There are 3-types of alpha subunits (HIF1-3alpha) and one HIF-beta subunits. However, the three HIF-alpha subunits are regulated by oxygen in a similar fashion, i.e. by regulated stabilization of the alpha-subunits. Under normal conditions, HIF-alpha Prolines are hydroxylated at Pro-402 and Pro-564. This allows binding of von Hippel-Lindau (VHL), the substrate recognition component of the E3 ubiquinated ligase complex, subsequent ubiquitination and degradation of HIF-alpha by the proteasome. Under hypoxic conditions, hydroxylation of HIF-alpha is inhibited and this prevents HIF-alpha degradation. The enzymes responsible for HIF-hydroxylation are known as HIF-prolyl hydroxylases (PHD1-3 or HPH1, HPH2, and HPH3). The three PHDs have been identified to hydroxylate the motif, LXXLAP* with *P being the hydroxyproline.