FAM20C

Family with sequence similarity 20, member C
Identifiers
Symbols FAM20C ; DMP-4; DMP4; GEF-CK; RNS
External IDs OMIM: 611061 MGI: 2136853 HomoloGene: 56879 GeneCards: FAM20C Gene
EC number 2.7.11.1
Orthologs
Species Human Mouse
Entrez 56975 80752
Ensembl ENSG00000177706 ENSMUSG00000025854
UniProt Q8IXL6 Q5MJS3
RefSeq (mRNA) NM_020223 NM_030565
RefSeq (protein) NP_064608 NP_085042
Location (UCSC) Chr 7:
0.19 – 0.26 Mb		 Chr 5:
138.75 – 138.81 Mb
PubMed search

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[8][9][10]

Clinical significance

Mutations in the FAM20C gene are associated with Raine syndrome.[3]

References

  1. ↑ 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.
  2. 1 2 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". The Journal of Biological Chemistry 282 (21): 15357–65. doi:10.1074/jbc.M701547200. PMID 17369251.
  3. 1 2 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 (Nov 2007). "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. doi:10.1086/522240. PMC 2265657. PMID 17924334.
  4. 1 2 3 Tagliabracci VS, Engel JL, Wen J, Wiley SE, Worby CA, Kinch LN, Xiao J, Grishin NV, Dixon JE (Jun 2012). "Secreted kinase phosphorylates extracellular proteins that regulate biomineralization". Science 336 (6085): 1150–3. doi:10.1126/science.1217817. PMC 3754843. PMID 22582013.
  5. ↑ Wang X, Hao J, Xie Y, Sun Y, Hernandez B, Yamoah AK, Prasad M, Zhu Q, Feng JQ, Qin C (Nov 2010). "Expression of FAM20C in the osteogenesis and odontogenesis of mouse". The Journal of Histochemistry and Cytochemistry 58 (11): 957–67. doi:10.1369/jhc.2010.956565. PMC 2958138. PMID 20644212.
  6. ↑ Yalak G, Vogel V (Dec 2012). "Extracellular phosphorylation and phosphorylated proteins: not just curiosities but physiologically important". Science Signaling 5 (255): re7. doi:10.1126/scisignal.2003273. PMID 23250399.
  7. ↑ Tagliabracci VS, Pinna LA, Dixon JE (Mar 2013). "Secreted protein kinases". Trends in Biochemical Sciences 38 (3): 121–30. doi:10.1016/j.tibs.2012.11.008. PMC 3582740. PMID 23276407.
  8. 1 2 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 (2012). "Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice". PLoS Genetics 8 (5): e1002708. doi:10.1371/journal.pgen.1002708. PMC 3355082. PMID 22615579.
  9. ↑ Wang X, Jung J, Liu Y, Yuan B, Lu Y, Feng JQ, Qin C (Nov 2013). "The specific role of FAM20C in amelogenesis". Journal of Dental Research 92 (11): 995–9. doi:10.1177/0022034513504588. PMC 3797537. PMID 24026952.
  10. ↑ Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, Qin C (Feb 2015). "The specific role of FAM20C in dentinogenesis". Journal of Dental Research 94 (2): 330–6. doi:10.1177/0022034514563334. PMC 4300304. PMID 25515778.

Further reading

  • 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". The Journal of Biological Chemistry 282 (21): 15357–65. doi:10.1074/jbc.M701547200. PMID 17369251. 
  • Simpson MA, Scheuerle A, Hurst J, Patton MA, Stewart H, Crosby AH (Mar 2009). "Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia". Clinical Genetics 75 (3): 271–6. doi:10.1111/j.1399-0004.2008.01118.x. PMID 19250384. 


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