Comprehensive analysis of the effects of P4ha1 and P4ha2 deletion on post-translational modifications of fibrillar collagens in mouse skin

A total of 421 site-specific PTMs were identified on fibrillar collagen chains (COL1A1, COL1A2, and COL3A1) extracted from wild-type mice skin. A total of 23 P4HA1-specific and seven P4HA2-specific 4-hydroxyproline sites on fibrillar collagen chains were identified. Moreover, it was found that the <i>P4ha1</i> and <i>P4ha2</i> deletion can affect the 3-hydroxyproline occupancy percentages in mice skin. Interestingly, increased levels of lysyl 5-hydroxylation were detected upon partial deletion of <i>P4ha1</i> and full deletion of <i>P4ha2</i>. These findings show that the effects of deletion of prolyl 4-hydroxylases are not limited to less 4-hydroxylation on some specific proline sites, but it can also modulate the prolyl 3-hydroxylation, lysyl 5-hydroxylation, and O-glycosylation occupancy percentages in the fibrillar collagen chains in a site-specific manner.