HIF Prolyl Hydroxylase 2

HIF prolyl hydroxylase 2 is a prolyl hydroxylase that modifies HIF-alpha. Classic prolyl hydroxylases are found in the endoplasmic reticulum and modify collagen, whereas HIF is an intracellular protein and the HPH sites do not resemble those modifying collagen. HIF is a transcriptional complex that plays a critical role in oxygen homeostasis. HPH is an essential component of the pathway through which cells sense oxygen. In the presence of oxygen, HPHs convert specific prolyl residues in HIF-alpha to hydroxyproline, leading to HIF-alpha destruction. Low oxygen levels, sensed at the cellular level, cause the HIF conversion to be reduced so that HIF is stable and there is increased angiogenesis. HPH-2, specifically, catalyzes the posttranslational formation of 4-hydroxyproline in HIF alpha proteins. It hydroxylates HIF-1 alpha at Pro(402) and Pro(564), and HIF-2 alpha. It targets HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitylation complex.