Extracellular serine/threonine protein kinase FAM20C

UniProtKB accession:  Q8IXL6

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UniProtKB description:  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 (PubMed:22582013, PubMed:23754375, PubMed:25789606). Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (PubMed:26091039). Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity (PubMed:26091039). Phosphorylates ERO1A, enhancing its activity which is required to maintain endoplasmic reticulum redox homeostasis and for oxidative protein folding (PubMed:29858230, PubMed:34349020). During endoplasmic reticulum stress, phosphorylates P4HB/PDIA1 which induces a functional switch, causing P4HB to change from an oxidoreductase to a molecular chaperone (PubMed:32149426). This is critical to maintain ER proteostasis and reduce cell death under ER stress (PubMed:32149426). 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 (PubMed:32149426). Required for osteoblast differentiation and mineralization (PubMed:34349020). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1/OPN (PubMed:22582013, PubMed:25789606, PubMed:34349020). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (PubMed:26091039).