40S ribosomal protein S19 explained

40S ribosomal protein S19 is a protein that in humans is encoded by the RPS19 gene.^{[1] [2]}

Function

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S19E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.^[2]

Clinical significance

Mutations in this gene cause Diamond–Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed.^[2]

Interactions

Ribosomal protein S19 has been shown to interact with basic fibroblast growth factor.^[3] RPS19 is also secreted extracellularly and its extracellular oligomers (crosslinked by the transglutaminase Coagulation factor XIII) is also known to bind and probably inhibit Macrophage migration inhibitory factor; though S19 oligomers themselves share MCIP's function as another very strong macrophage chemoattractant and bind to anaphylotoxin C5 receptor^[4]

Further reading

• Wool IG, Chan YL, Glück A . Structure and evolution of mammalian ribosomal proteins . Biochem. Cell Biol. . 73 . 11–12 . 933–47 . 1996 . 8722009 . 10.1139/o95-101 .
• Morimoto K, Lin S, Sakamoto K . The functions of RPS19 and their relationship to Diamond-Blackfan anemia: a review . Mol. Genet. Metab. . 90 . 4 . 358–62 . 2007 . 17178250 . 10.1016/j.ymgme.2006.11.004 .
• Yamamoto T . Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes . Pathol. Int. . 57 . 1 . 1–11 . 2007 . 17199736 . 10.1111/j.1440-1827.2007.02049.x . 22946804 .
• Kondoh N, Schweinfest CW, Henderson KW, Papas TS . Differential expression of S19 ribosomal protein, laminin-binding protein, and human lymphocyte antigen class I messenger RNAs associated with colon carcinoma progression and differentiation . Cancer Res. . 52 . 4 . 791–6 . 1992 . 1339304 .
• Vladimirov SN, Ivanov AV, Karpova GG, Musolyamov AK, Egorov TA, Thiede B, Wittmann-Liebold B, Otto A . Characterization of the human small-ribosomal-subunit proteins by N-terminal and internal sequencing, and mass spectrometry . Eur. J. Biochem. . 239 . 1 . 144–9 . 1996 . 8706699 . 10.1111/j.1432-1033.1996.0144u.x . free .
• Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N . The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia . Nat. Genet. . 21 . 2 . 169–75 . 1999 . 9988267 . 10.1038/5951 . 26664929 .
• Willig TN, Draptchinskaia N, Dianzani I, Ball S, Niemeyer C, Ramenghi U, Orfali K, Gustavsson P, Garelli E, Brusco A, Tiemann C, Pérignon JL, Bouchier C, Cicchiello L, Dahl N, Mohandas N, Tchernia G . Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression . Blood . 94 . 12 . 4294–306 . 2000 . 10590074 .
• Matsson H, Klar J, Draptchinskaia N, Gustavsson P, Carlsson B, Bowers D, de Bont E, Dahl N . Truncating ribosomal protein S19 mutations and variable clinical expression in Diamond-Blackfan anemia . Hum. Genet. . 105 . 5 . 496–500 . 2000 . 10598818 . 10.1007/s004390051136 .
• Tentler D, Gustavsson P, Elinder G, Eklöf O, Gordon L, Mandel A, Dahl N . A microdeletion in 19q13.2 associated with mental retardation, skeletal malformations, and Diamond-Blackfan anaemia suggests a novel contiguous gene syndrome . J. Med. Genet. . 37 . 2 . 128–31 . 2000 . 10662814 . 1734524 . 10.1136/jmg.37.2.128 .
• Ramenghi U, Campagnoli MF, Garelli E, Carando A, Brusco A, Bagnara GP, Strippoli P, Izzi GC, Brandalise S, Riccardi R, Dianzani I . Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population . Blood Cells Mol. Dis. . 26 . 5 . 417–22 . 2001 . 11112378 . 10.1006/bcmd.2000.0324 .
• Nishimura T, Horino K, Nishiura H, Shibuya Y, Hiraoka T, Tanase S, Yamamoto T . Apoptotic cells of an epithelial cell line, AsPC-1, release monocyte chemotactic S19 ribosomal protein dimer . J. Biochem. . 129 . 3 . 445–54 . 2001 . 11226885 . 10.1093/oxfordjournals.jbchem.a002876 .
• Soulet F, Al Saati T, Roga S, Amalric F, Bouche G . Fibroblast growth factor-2 interacts with free ribosomal protein S19 . Biochem. Biophys. Res. Commun. . 289 . 2 . 591–6 . 2002 . 11716516 . 10.1006/bbrc.2001.5960 .
• Shibuya Y, Shiokawa M, Nishiura H, Nishimura T, Nishino N, Okabe H, Takagi K, Yamamoto T . Identification of Receptor-Binding Sites of Monocyte Chemotactic S19 Ribosomal Protein Dimer . Am. J. Pathol. . 159 . 6 . 2293–301 . 2001 . 11733378 . 1850605 . 10.1016/S0002-9440(10)63079-9 .
• Li B, Sun M, He B, Yu J, Zhang YD, Zhang YL . Identification of differentially expressed genes in human uterine leiomyomas using differential display . Cell Res. . 12 . 1 . 39–45 . 2004 . 11942409 . 10.1038/sj.cr.7290108 . free .
• Da Costa L, Tchernia G, Gascard P, Lo A, Meerpohl J, Niemeyer C, Chasis JA, Fixler J, Mohandas N . Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology . Blood . 101 . 12 . 5039–45 . 2004 . 12586610 . 10.1182/blood-2002-12-3878 . free .
• Shrestha A, Shiokawa M, Nishimura T, Nishiura H, Tanaka Y, Nishino N, Shibuya Y, Yamamoto T . Switch Moiety in Agonist/Antagonist Dual Effect of S19 Ribosomal Protein Dimer on Leukocyte Chemotactic C5a Receptor . Am. J. Pathol. . 162 . 4 . 1381–8 . 2003 . 12651630 . 1851224 . 10.1016/S0002-9440(10)63934-X .
• Proust A, Da Costa L, Rince P, Landois A, Tamary H, Zaizov R, Tchernia G, Delaunay J . Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene . Hematol. J. . 4 . 2 . 132–6 . 2003 . 12750732 . 10.1038/sj.thj.6200230 . SHIP Working Group on DBA .

External links

• GeneReviews/NCBI/NIH/UW entry on Diamond–Blackfan Anemia
• OMIM entries on Diamond–Blackfan Anemia

Notes and References

1. Kenmochi N, Kawaguchi T, Rozen S, Davis E, Goodman N, Hudson TJ, Tanaka T, Page DC . A map of 75 human ribosomal protein genes . Genome Res . 8 . 5 . 509–23 . August 1998 . 9582194 . 10.1101/gr.8.5.509 . free .
2. Web site: Entrez Gene: RPS19 ribosomal protein S19.
3. Soulet F, Al Saati T, Roga S, Amalric F, Bouche G . Fibroblast growth factor-2 interacts with free ribosomal protein S19 . Biochem. Biophys. Res. Commun. . 289 . 2 . 591–6 . November 2001 . 11716516 . 10.1006/bbrc.2001.5960 .
4. Molecular Basis of Cell and Developmental Biology: Ana-Maria Filip, Jörg Klug, Sevil Cayli, Suada Fröhlich, Tamara Henke, Philipp Lacher, Regina Eickhoff, Patrick Bulau, Monika Linder, Christine Carlsson-Skwirut, Lin Leng, Richard Bucala, Sandra Kraemer, Jürgen Bernhagen, and Andreas Meinhardt. "Ribosomal Protein S19 Interacts with Macrophage Migration Inhibitory Factor and Attenuates Its Pro-inflammatory Function"' J. Biol. Chem. 2009 284: 7977–7985. First Published on January 20, 2009, doi:10.1074/jbc.M808620200