Protein-coding gene in the species Homo sapiens
FAM20C |
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Identifiers |
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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 |
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External IDs | OMIM: 611061; MGI: 2136853; HomoloGene: 56879; GeneCards: FAM20C; OMA:FAM20C - orthologs |
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Gene location (Human) |
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![Chromosome 7 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/9/99/Ideogram_human_chromosome_7.svg/300px-Ideogram_human_chromosome_7.svg.png) | Chr. | Chromosome 7 (human)[1] |
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| Band | 7p22.3 | Start | 192,571 bp[1] |
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End | 260,772 bp[1] |
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Gene location (Mouse) |
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![Chromosome 5 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/c/c0/Ideogram_house_mouse_chromosome_5.svg/260px-Ideogram_house_mouse_chromosome_5.svg.png) | Chr. | Chromosome 5 (mouse)[2] |
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| Band | 5|5 G2 | Start | 138,740,269 bp[2] |
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End | 138,795,832 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - right lobe of liver
- body of stomach
- ascending aorta
- human kidney
- Descending thoracic aorta
- popliteal artery
- tibial arteries
- muscle layer of sigmoid colon
- right coronary artery
- left coronary artery
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| Top expressed in | - molar
- right kidney
- medial geniculate nucleus
- islet of Langerhans
- medial dorsal nucleus
- olfactory bulb
- stria vascularis
- proximal tubule
- lateral geniculate nucleus
- left lobe of liver
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - transferase activity
- nucleotide binding
- calcium ion binding
- manganese ion binding
- metal ion binding
- kinase activity
- protein binding
- ATP binding
- protein serine/threonine kinase activity
- phosphotransferase activity, alcohol group as acceptor
| Cellular component | - Golgi apparatus
- extracellular region
- extracellular exosome
- extracellular space
- cytoplasm
- endoplasmic reticulum lumen
| Biological process | - skeletal system development
- phosphorylation
- positive regulation of bone mineralization
- osteoclast maturation
- biomineral tissue development
- regulation of fibroblast growth factor receptor signaling pathway
- dentinogenesis
- regulation of phosphorus metabolic process
- protein phosphorylation
- positive regulation of osteoblast differentiation
- enamel mineralization
- odontoblast differentiation
- ATP metabolic process
- post-translational protein modification
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | |
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ENSG00000177706 ENSG00000281429 ENSG00000282147 ENSG00000288499 |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 7: 0.19 – 0.26 Mb | Chr 5: 138.74 – 138.8 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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]
References
- ^ a b c ENSG00000281429, ENSG00000282147, ENSG00000288499 GRCh38: Ensembl release 89: ENSG00000177706, ENSG00000281429, ENSG00000282147, ENSG00000288499 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025854 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ 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". The Journal of Biological Chemistry. 282 (21): 15357–65. doi:10.1074/jbc.M701547200. PMID 17369251.
- ^ 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 (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.
- ^ a b c 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ 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. S2CID 22696170.
Extracellular matrix | |
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Other | |
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