FAM20C

Last updated
FAM20C
Identifiers
Aliases FAM20C , DMP-4, DMP4, GEF-CK, RNS, family with sequence similarity 20 member C, G-CK, golgi associated secretory pathway kinase, FAM20C golgi associated secretory pathway kinase
External IDs OMIM: 611061 MGI: 2136853 HomoloGene: 56879 GeneCards: FAM20C
Orthologs
SpeciesHumanMouse
Entrez
Ensembl

Contents

UniProt
RefSeq (mRNA)

NM_020223

NM_030565
NM_001359593

RefSeq (protein)

NP_064608

NP_085042
NP_001346522

Location (UCSC) Chr 7: 0.19 – 0.26 Mb Chr 5: 138.74 – 138.8 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] [6] [7] 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. [8]

Function

Dmp4 causes differentiation of mesenchymal stem cells into functional odontoblast cells and is likely to function as a regulator of dentin mineralization. [6] [9] FAM20C is a secretory kinase, responsible for the phosphorylation of all secreted proteins, from milk to bone proteins. [8] 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. [8] [10] [11] 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), [12] 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) [12] [13] [14]

Clinical significance

Mutations in the FAM20C gene are associated with Raine syndrome. [7]

Related Research Articles

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<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Cyclin-dependent kinase 1</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">Casein kinase 2, alpha 1</span> Protein and coding gene in humans

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<span class="mw-page-title-main">PAK1</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">MAPKAPK2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MAP2K6</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CSNK2B</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PRKCI</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MAP2K7</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TANK-binding kinase 1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SGK3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PRKD3</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase D3 (PKD3) or PKC-nu is an enzyme that in humans is encoded by the PRKD3 gene.

<span class="mw-page-title-main">DMP1</span> Protein-coding gene in the species Homo sapiens

Dentin matrix acidic phosphoprotein 1 is a protein that in humans is encoded by the DMP1 gene.

<span class="mw-page-title-main">CARD11</span> Protein-coding gene in the species Homo sapiens

Caspase recruitment domain-containing protein 11 also known as CARD-containing MAGUK protein 1 is a protein in the CARD-CC protein family that in humans is encoded by the CARD11 gene. CARD 11 is a membrane associated protein that is found in various human tissues, including the thymus, spleen, liver, and peripheral blood leukocytes. Similarly, CARD 11 is also found in abundance in various lines of cancer cells.

<span class="mw-page-title-main">GRK4</span> Protein-coding gene in the species Homo sapiens

G protein-coupled receptor kinase 4 (GRK4) is an enzyme that is encoded by the GRK4 gene in humans.

<span class="mw-page-title-main">STK3</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase 3 is an enzyme that in humans is encoded by the STK3 gene.

<span class="mw-page-title-main">DYRK2</span> Protein-coding gene in humans

Dual specificity tyrosine-phosphorylation-regulated kinase 2 is an enzyme, in particular a dual-specificity kinase, that in humans is encoded by the DYRK2 gene.

Dentin sialoprotein is a protein found in teeth. It is one of the two proteins produced by the segmentation of dentin sialophosphoprotein. Dentin sialoprotein can be found in the dentin immediately subjacent to cellular cementum, but not subjacent to acellular fibrous cementum.

<span class="mw-page-title-main">G protein-coupled receptor kinase 3</span> Protein-coding gene in the species Homo sapiens

G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2 gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2), and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK2.

References

  1. 1 2 3 ENSG00000281429, ENSG00000282147, ENSG00000288499 GRCh38: Ensembl release 89: ENSG00000177706, ENSG00000281429, ENSG00000282147, ENSG00000288499 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025854 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. 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.
  7. 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.
  8. 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. Bibcode:2012Sci...336.1150T. doi:10.1126/science.1217817. PMC   3754843 . PMID   22582013.
  9. 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.
  10. 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. S2CID   205449.
  11. 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.
  12. 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.
  13. 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.
  14. 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