FAM20C explained

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]

Further reading

Notes and References

  1. Nalbant D, Youn H, Nalbant SI, Sharma S, Cobos E, Beale EG, Du Y, Williams SC . FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells . BMC Genomics . 6 . 11 . 2005 . 15676076 . 548683 . 10.1186/1471-2164-6-11 . free .
  2. Hao J, Narayanan K, Muni T, Ramachandran A, George A . 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 . 17369251 . 10.1074/jbc.M701547200 . free .
  3. 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 . 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 . 17924334 . 2265657 . 10.1086/522240 .
  4. Tagliabracci VS, Engel JL, Wen J, Wiley SE, Worby CA, Kinch LN, Xiao J, Grishin NV, Dixon JE . Secreted kinase phosphorylates extracellular proteins that regulate biomineralization . Science . 336 . 6085 . 1150–3 . Jun 2012 . 22582013 . 3754843 . 10.1126/science.1217817 . 2012Sci...336.1150T .
  5. Wang X, Hao J, Xie Y, Sun Y, Hernandez B, Yamoah AK, Prasad M, Zhu Q, Feng JQ, Qin C . Expression of FAM20C in the osteogenesis and odontogenesis of mouse . The Journal of Histochemistry and Cytochemistry . 58 . 11 . 957–67 . Nov 2010 . 20644212 . 2958138 . 10.1369/jhc.2010.956565 .
  6. Yalak G, Vogel V . Extracellular phosphorylation and phosphorylated proteins: not just curiosities but physiologically important . Science Signaling . 5 . 255 . re7 . Dec 2012 . 23250399 . 10.1126/scisignal.2003273 . 205449 .
  7. Tagliabracci VS, Pinna LA, Dixon JE . Secreted protein kinases . Trends in Biochemical Sciences . 38 . 3 . 121–30 . Mar 2013 . 23276407 . 3582740 . 10.1016/j.tibs.2012.11.008 .
  8. 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 JQ, Qin C . Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice . PLOS Genetics . 8 . 5 . e1002708 . 2012 . 22615579 . 3355082 . 10.1371/journal.pgen.1002708 . free .
  9. Wang X, Jung J, Liu Y, Yuan B, Lu Y, Feng JQ, Qin C . The specific role of FAM20C in amelogenesis . Journal of Dental Research . 92 . 11 . 995–9 . Nov 2013 . 24026952 . 3797537 . 10.1177/0022034513504588 .
  10. Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, Qin C . The specific role of FAM20C in dentinogenesis . Journal of Dental Research . 94 . 2 . 330–6 . Feb 2015 . 25515778 . 4300304 . 10.1177/0022034514563334 .

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