Fig 2.

Schematic model of the structure of the HIF hydroxylases and naturally occurring activators and inhibitors of their activity. All hydroxylases have a conserved dioxygenase domain at the C-terminal ends. PHD2 contains a zf-MYND (zinc-finger domain) that may interact with regulatory proteins. Both PHD1 and PHD2 contain potential subcellular localization signal sequences, nuclear localization signal or nuclear export signal. The known inhibitors, such as TCA cycle intermediates (TCA IMs) affect the enzymatic activity of the hydroxylases. The expression or activity of the hydroxylases can also be modulated in a post-translational manner (PT). The activators mainly increase the hydroxylase expression by activating transcription (T).