Recombinant Human Extracellular serine/threonine protein kinase FAM20C (FAM20C)

Function

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)

Subcellular Location

Golgi apparatus membrane (Single-pass type II membrane protein); Secreted; Endoplasmic reticulum

Disease Association

Raine syndrome (RNS) : An autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome, although some patients survive into childhood. Clinical features include generalized increase in the density of all bones and a marked increase in the ossification of the skull, craniofacial dysplasia and microcephaly. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed

Subunit

Homodimer; disulfide-linked (PubMed:34349020). Interacts with FAM20A; probably forming a heterotetramer of 2 subunits of FAM20A and 2 subunits of FAM20C (PubMed:25789606). Interacts with protease MBTPS1/S1P; the interaction results in FAM20C cleavage and secretion (PubMed:34349020). Interacts with COPII components SEC23A and SEC24A; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles (PubMed:34349020)

• Wu C. et al. PubMed: CI-EB1PS1GRQV6JF (JUL-)
• Kitagawa H. et al. Molecular cloning and characterization of a novel xylosylkinase. (FEB-)
• Hillier L.W. et al. The DNA sequence of human chromosome 7. — Nature (2003)
• Scherer S.W. et al. Human chromosome 7: DNA sequence and biology. — Science (2003)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• Tagliabracci V.S. et al. A single kinase generates the majority of the secreted phosphoproteome. — Cell (2015)