FAM20C
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 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 SCPP proteins[9][10][11]
Clinical significance
Mutations in the FAM20C gene are associated with Raine syndrome.[3]
References
- ^ Nalbant D, Youn H, Nalbant SI, Sharma S, Cobos E, Beale EG, Du Y, Williams SC (2005). "FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells". BMC Genomics. 6: 11. doi:10.1186/1471-2164-6-11. PMC 548683. PMID 15676076.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Hao J, Narayanan K, Muni T, Ramachandran A, George A (May 2007). "Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation". J. Biol. Chem. 282 (21): 15357–65. doi:10.1074/jbc.M701547200. PMID 17369251.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Simpson MA, Hsu R, Keir LS, Hao J, Sivapalan G, Ernst LM, Zackai EH, Al-Gazali LI, Hulskamp G, Kingston HM, Prescott TE, Ion A, Patton MA, Murday V, George A, Crosby AH (November 2007). "Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development". Am. J. Hum. Genet. 81 (5): 906–12. doi:10.1086/522240. PMC 2265657. PMID 17924334.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b c Tagliabracci VS, Engel JL, Wen J, Wiley SE, Worby CA, Kinch LN, Xiao J, Grishin NV, Dixon JE (2012). "Secreted kinase phosphorylates extracellular proteins that regulate biomineralization". Science. 336 (6085): 1150–3. doi:10.1126/science.1217817. PMC 3754843. PMID 22582013.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Wang X, Hao J, Xie Y, Sun Y, Hernandez B, Yamoah AK, Prasad M, Zhu Q, Feng JQ, Qin C. (2010). "Expression of FAM20C in the osteogenesis and odontogenesis of mouse". J Histochem Cytochem. 58 (11): 957–67. doi:10.1369/jhc.2010.956565. PMC 2958138. PMID 20644212.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Yalak G, Vogel V (December 2012). "Extracellular phosphorylation and phosphorylated proteins: not just curiosities but physiologically important". Sci Signal. 5 (255): re7. doi:10.1126/scisignal.2003273. PMID 23250399.
- ^ Tagliabracci VS, Pinna LA, Dixon JE (2013). "Secreted protein kinases". Trends Biochem. Sci. 38 (3): 121–30. doi:10.1016/j.tibs.2012.11.008. PMC 3582740. PMID 23276407.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Wang X, Wang S,Li C, Gao T, Liu Y, Rangiani A, Sun Y, Hao J, George A, Lu Y, Groppe J, Yuan B, Feng J, Qin CL (2012). "Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice". PLoS Genet. 8 (5): e1002708. doi:10.1371/journal.pgen.1002708. PMC 3355082. PMID 22615579.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Wang X, Wang S, Lu Y, Gibson MP, Liu Y, Yuan B, Feng JQ, Qin C. (2012). "FAM20C plays an essential role in the formation of murine teeth". J Biol Chem. 8 (5): e1002708. doi:10.1371/journal.pgen.1002708. PMC 3355082. PMID 22615579.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Wang X, Jung J, Liu Y, Yuan B, Lu Y, Feng JQ, Qin C. (2013). "The specific role of FAM20C in amelogenesis". J Dent Res. 92 (11): 995–9. doi:10.1177/0022034513504588. PMC 3797537. PMID 24026952.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, Qin C. (2015). "The specific role of FAM20C in dentinogenesis". J Dent Res. 94 (2): 330–6. doi:10.1177/0022034514563334. PMC 4300304. PMID 25515778.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
Further reading
- Hao J, Narayanan K, Muni T, Ramachandran A, George A (2007). "Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation". J. Biol. Chem. 282 (21): 15357–65. doi:10.1074/jbc.M701547200. PMID 17369251.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Simpson MA, Scheuerle A, Hurst J, Patton MA, Stewart H, Crosby AH (2009). "Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia". Clin. Genet. 75 (3): 271–6. doi:10.1111/j.1399-0004.2008.01118.x. PMID 19250384.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
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