Disease relevance of P4HTM

• Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress [1].
• P4H-TM levels in cultured cells are increased by hypoxia, and P4H-TM is N-glycosylated and is located in endoplasmic reticulum membranes with its catalytic site inside the lumen, a location differing from those of the HIF-P4Hs [2].

High impact information on P4HTM

• Such behavior was also shown by recombinant AH1, PH2, and PH4 proteins after expression in Pichia pastoris [3].
• Prolyl 4-hydroxylases (PH4) catalyze the formation of 4-hydroxyproline in collagens, the major components of the ECM, and are implicated in the hydroxylation of proline in several other secreted proteins [4].
• Significant growth occurred beyond stages PH3 (PH4 6.54 mm, PH5 8.98 mm) and B3 (B4 7.25 mm, B5 9.41 mm) and from less than 1 year prior to menarche to more than 1 year after menarche (5.92 mm for girls less than 1 year premenarche, 7.88 mm for girls in their first year after menarche, and 9.05 mm for girls more than 1 year beyond menarche) [5].
• Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors [6].
• Like EGLNs, PH-4 overexpressed in cellular reporter assays suppressed the HIF transactivation activity, dependent on the consensus ODDD proline residues [6].

Biological context of P4HTM

• We identified a novel putative proline 4-hydroxylase, PH-4, with an aminoterminal EF-hand motif and a carboxyterminal catalytic domain, which was highly expressed in most organs, and-unlike EGLNs which localize to the cytoplasm and nucleus-was associated with the endoplasmic reticulum [6].

References