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] The discovery of FAM20C, is largely unexplored, with an unknown number of secreted protein kinases yet to be identified.[5][6]
Function
Dmp4 causes differentiation of mesenchymal stem cells into functional odontoblast cells and is likely to function as a regulator of dentin mineralization.[2] In 2010 the Dixon group discovered that this protein represents the secretory kinase, responsible for the phosphorylation of all secreted proteins, from milk to bone proteins (Tagliabracci et al, Science 2012)[7] Phosphorylation by Fam20C in the secretory pathway is robust and 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][8]
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.
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: 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.
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: 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.
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: CS1 maint: multiple names: authors list (link) - ^ a b Tagliabracci et al., 2012
- ^ Tagliabracci et al., 2013
- ^ Yalak and Vogel, 2012
- ^ Cite error: The named reference
pmid22582013
was invoked but never defined (see the help page). - ^ Yalak and Vogel, 2012.
Further reading
- Scherer SW, Cheung J, MacDonald JR; et al. (2003). "Human chromosome 7: DNA sequence and biology". Science. 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
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: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
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: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
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: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - Hao J, Narayanan K, Muni T; et al. (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}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Strausberg RL, Feingold EA, Grouse LH; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
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: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - Simpson MA, Scheuerle A, Hurst J; et al. (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.
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: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link)
- V.S. Tagliabracci, J.L. Engel, J. Wen, S.E. Wiley, C.A. Worby, L.N. Kinch, J. Xiao, N.V. Grishin, J.E. Dixon
Secreted kinase phosphorylates extracellular proteins that regulate biomineralization Science, 336 (2012), pp. 1150–1153
- G. Yalak, V. Vogel
Extracellular phosphorylation and phosphorylated proteins: not just curiosities but physiologically important Sci. Signal., 5 (2012), p. re7
- V.S. Tagliabracci, L.A. Pinna, J.E. Dixon
Secreted protein kinases Trends Biochem. Sci., 38 (2013), pp. 121–130