Prolyl 4-hydroxylase subunit alpha-1 (P4HA1)

Prolyl 4-hydroxylase subunit alpha-1 (P4HA1) is the major alpha catalytic subunit of prolyl 4-hydroxylase, a tetrameric enzyme (α2β2) necessary for the post-translational hydroxylation of proline residues in collagen molecules—a modification essential for the stability and proper folding of collagen triple helices[1][3][5]. The enzyme is key to the biosynthesis of collagens and, by extension, proper extracellular matrix structure and tissue integrity[1][3][4]. P4HA1 is the primary isoform among alpha catalytic subunits, highly expressed in tissues such as the testis, placenta, fibroblasts, and in various cancer types[2][4]. Dysregulated expression is implicated in cancer cell proliferation, invasion, metastasis, and chemoresistance through effects on extracellular matrix dynamics and hypoxic adaptation pathways[2][4]. Reduced activity or genetic knockdown impairs collagen deposition and modifies tumor environment vasculature, highlighting a key safety concern if targeted therapeutically[4]. No specific small-molecule drugs are currently approved for clinical use targeting P4HA1, but several preclinical inhibitors and RNA-based strategies are being explored for cancer and fibrotic diseases[2][4].

Other names

Prolyl 4-hydroxylase subunit alpha-1P4HA1P4HA4-PH alpha-1C-P4Halpha(I)collagen prolyl 4-hydroxylase alpha(I)Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1prolyl 4-hydroxylase alpha polypeptide Iprocollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide I

Enzyme inhibition: Small molecules or RNA interference (RNAi) can inhibit P4HA1 to reduce collagen hydroxylation, disrupt extracellular matrix remodeling, or alter tumor progression. Regulation by miRNA: miR-30e, miR-122, etc. can suppress P4HA1 expression, impacting cell migration, proliferation, and EMT (epithelial-mesenchymal transition).