HIF-prolyl hydroxylase PH-4; hypoxia-inducible factor prolyl 4-hydroxylase (PH4, P4HTM)
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Function
- may catalyze posttranslational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins
- may function as a cellular oxygen sensor
- under normoxic conditions, may target HIF (via hydroxylation) for proteasomal degradation via the von Hippel-Lindau ubiquitination complex
HIF alpha chain L-proline + 2-oxoglutarate + O2 <--> HIF alpha chain trans-4-hydroxy-L-proline + succinate + CO2
Cofactors: Fe+2/Fe+3, ascorbate
Structure
- contains 2 EF-hand domains
- contains 1 PKHD domain (prolyl/lysyl hydroxylase domain)
Compartment
endoplasmic reticulum membrane, peripheral membrane
Alternative splicing
named isoforms=3
Expression
- widely expressed
- highest levels in brain, kidney, adrenal gland