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 .
Subcellular locations: Golgi apparatus membrane, Secreted, Endoplasmic reticulum
Resides in the Golgi apparatus membrane and is secreted following propeptide cleavage . Retained in the endoplasmic reticulum (ER) in response to ER stress where it phosphorylates P4HB .
Widely expressed.