Prolyl hydroxylase 4 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 prolyl hydroxylase sites do not resemble those modifying collagen. HIF is a transcriptional complex that plays a critical role in oxygen homeostasis. Prolyl hydroxylase is an essential component of the pathway through which cells sense oxygen. In the presence of oxygen, prolyl hydroxylases 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. Prolyl hydroxylase 4, specifically, catalyzes the posttranslational formation of 4-hydroxyproline in HIF alpha proteins. It may function as a cellular oxygen sensor and, under normoxic conditions, may targets HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitylation complex.
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Protein Aliases: FLJ20262; HIF-PH4; HIF-prolyl hydroxylase 4; HPH-4; hypoxia inducible factor prolyl 4 hydroxylase; hypoxia-inducible factor prolyl 4-hydroxylase; Hypoxia-inducible factor prolyl hydroxylase 4; P4H TM; P4H with transmembrane domain; P4H-TM; PH 4; proline 4-hydroxylase; prolyl 4-hydroxylase, transmembrane; prolyl 4-hydroxylase, transmembrane (endoplasmic reticulum); Prolyl hydroxlase domain-containing 4; Transmembrane prolyl 4-hydroxylase
Gene Aliases: 4933406E20Rik; AI853847; BB128974; EGLN4; HIFPH4; P4H-TM; P4HTM; PH-4; PH4; PHD4; RGD1311848
Molecular Function: protein modifying enzyme