Prolyl hydroxylase 3 (PHD3) is a 27kD enzyme expressed abundantly in all tissues with the highest expression in testis. Hypoxia inducible factor-1 (HIF-1) is a transcriptional complex, consisting of an alpha and beta subunit, which plays a key role in coordinating the cellular response to hypoxia. During normal oxygen conditions, the alpha subunit of HIF-1 is rapidly degraded, however when hypoxia occurs this degradation is suppressed and HIF-1 activates the transcription of various genes important for survival and adaptation to hypoxia. Prolyl hydroxylase 3 catalyses the hydroxylation of specific prolyl residues within the HIF-1 alpha subunit, thereby targeting this subunit for degradation. Prolyl hydroxylase 3 might also play a role in cell growth regulation in muscle cells and apoptosis in neuronal tissue.
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