Prolyl 4-hydroxylase subunit alpha-2 (P4HA2)

Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) is an essential enzyme involved in collagen biosynthesis, catalyzing the hydroxylation of proline residues in -X–Pro–Gly– motifs— a modification required for proper collagen triple-helix formation and extracellular matrix assembly[1][3]. The enzyme is a tetramer composed of two identical alpha and two beta subunits, with P4HA2 forming a major part of the catalytic site[3]. P4HA2 is transcriptionally regulated and participates in the post-translational maturation of collagens and related proteins[1][3]. Aberrant expression of P4HA2 drives tumor progression, invasion, metastasis, and poor outcomes, predominantly by enhancing collagen deposition, modulating extracellular matrix structure, and promoting oncogenic pathways like glycolysis and epithelial–mesenchymal transition[1][2]. It is recognized as an emerging therapeutic target and biomarker in oncology and fibrotic diseases, though targeting it presents therapeutic challenges due to its central physiological role in collagen metabolism[1][2][3].

Other names

Prolyl 4-hydroxylase, alpha polypeptide IICollagen prolyl 4-hydroxylase subunit alpha-2C-P4Halpha(II)4-PH alpha-2Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-2Collagen prolyl 4-hydroxylase alpha(II)Procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide IIP4H alpha 2

Inhibition of collagen prolyl 4-hydroxylase activity impairs collagen maturation and deposition[2]. It suppresses tumor cell proliferation, invasion, migration, and induces apoptosis via modulation of the extracellular matrix and glycolysis pathway[2].