Biology:FAM20C
 Generic protein structure example |
Family with sequence similarity 20, member C also known as FAM20C or DMP4 is a protein which in humans is encoded by the FAM20C gene.[1][2][3] Fam20C, a Golgi localized protein kinase, is a serine kinase that phosphorylates both casein and other highly acidic proteins and members of the small integrin-binding ligand, the N-linked glycoproteins (SIBLING) family at the target motif SerXGlu.[4]
Function
Dmp4 causes differentiation of mesenchymal stem cells into functional odontoblast cells and is likely to function as a regulator of dentin mineralization.[2][5] FAM20C is a secretory kinase, responsible for the phosphorylation of all secreted proteins, from milk to bone proteins.[4] Phosphorylation by Fam20C in the secretory pathway is essential for proper biomineralization of bone. The substrate specificity of FAM20C indicates, however, that it is not likely to account for the tyrosine phosphorylation of the secreted protein. The characterization of FAM20C as an active serine kinase in the Golgi apparatus provides a clear precedent that ATP dependent protein phosphorylation can take place in the secretory apparatus.[4][6][7] Fam20C knockout mice develop severe hypophosphatemic rickets due to an increased renal phosphate wasting that is likely attributed to the remarkable elevation of serum fibroblast growth factor 23 (FGF23),[8] while their dentin and enamel defects are largely independent from the hypophosphatemia and appear to be a local effects of phosphorylation failure in the secretory calcium-binding phosphoproteins (SCPPs)[8][9][10]
Clinical significance
Mutations in the FAM20C gene are associated with Raine syndrome.[3]
References
- ↑ "FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells". BMC Genomics 6: 11. 2005. doi:10.1186/1471-2164-6-11. PMID 15676076.
- ↑ 2.0 2.1 "Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation". The Journal of Biological Chemistry 282 (21): 15357–65. May 2007. doi:10.1074/jbc.M701547200. PMID 17369251.
- ↑ 3.0 3.1 "Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development". American Journal of Human Genetics 81 (5): 906–12. Nov 2007. doi:10.1086/522240. PMID 17924334.
- ↑ 4.0 4.1 4.2 "Secreted kinase phosphorylates extracellular proteins that regulate biomineralization". Science 336 (6085): 1150–3. Jun 2012. doi:10.1126/science.1217817. PMID 22582013.
- ↑ "Expression of FAM20C in the osteogenesis and odontogenesis of mouse". The Journal of Histochemistry and Cytochemistry 58 (11): 957–67. Nov 2010. doi:10.1369/jhc.2010.956565. PMID 20644212.
- ↑ "Extracellular phosphorylation and phosphorylated proteins: not just curiosities but physiologically important". Science Signaling 5 (255): re7. Dec 2012. doi:10.1126/scisignal.2003273. PMID 23250399.
- ↑ "Secreted protein kinases". Trends in Biochemical Sciences 38 (3): 121–30. Mar 2013. doi:10.1016/j.tibs.2012.11.008. PMID 23276407.
- ↑ 8.0 8.1 "Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice". PLOS Genetics 8 (5): e1002708. 2012. doi:10.1371/journal.pgen.1002708. PMID 22615579.
- ↑ "The specific role of FAM20C in amelogenesis". Journal of Dental Research 92 (11): 995–9. Nov 2013. doi:10.1177/0022034513504588. PMID 24026952.
- ↑ "The specific role of FAM20C in dentinogenesis". Journal of Dental Research 94 (2): 330–6. Feb 2015. doi:10.1177/0022034514563334. PMID 25515778.
Further reading
- "Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation". The Journal of Biological Chemistry 282 (21): 15357–65. May 2007. doi:10.1074/jbc.M701547200. PMID 17369251.
- "Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia". Clinical Genetics 75 (3): 271–6. Mar 2009. doi:10.1111/j.1399-0004.2008.01118.x. PMID 19250384.
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