Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth. Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome. Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity. Phosphorylates ERO1A, enhancing its activity which is required to maintain endoplasmic reticulum redox homeostasis and for oxidative protein folding. During endoplasmic reticulum stress, phosphorylates P4HB/PDIA1 which induces a functional switch, causing P4HB to change from an oxidoreductase to a molecular chaperone. This is critical to maintain ER proteostasis and reduce cell death under ER stress. Phosphorylation of P4HB also promotes its interaction with ERN1, leading to reduced activity of ERN1, a key sensor for the endoplasmic reticulum unfolded protein response. Required for osteoblast differentiation and mineralization. Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1/OPN. In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion.
