CD20: Wikis

  

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Membrane-spanning 4-domains, subfamily A, member 1
Identifiers
Symbols MS4A1; B1; Bp35; CD20; LEU-16; MGC3969; MS4A2; S7
External IDs OMIM112210 MGI88321 HomoloGene7259 GeneCards: MS4A1 Gene
RNA expression pattern
PBB GE MS4A1 210356 x at tn.png
PBB GE MS4A1 217418 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 931 12482
Ensembl ENSG00000156738 ENSMUSG00000024673
UniProt P11836 Q542S5
RefSeq (mRNA) NM_021950 NM_007641
RefSeq (protein) NP_068769 NP_031667
Location (UCSC) Chr 11:
59.98 - 59.99 Mb
Chr 19:
11.32 - 11.33 Mb
PubMed search [2] [3]

CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells.

B-lymphocyte antigen CD20 is a protein that in humans is encoded by the MS4A1 gene.[1][2]

This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This gene encodes a B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants which encode the same protein.[2]

Contents

Function

The protein has no known natural ligand[3] and its function is unclear. It is suspected that it acts as a calcium channel in the cell membrane.

Expression

CD20 is expressed on all stages of B cell development except the first and last; it is present from pre-pre B cells through memory cells, but not on either pro-B cells or plasma cells.[4]

It is found on B-cell lymphomas, hairy cell leukemia, and B-cell chronic lymphocytic leukemia. It is also found on skin/melanoma cancer stem cells.[5]

Clinical significance

It is the target of the monoclonal antibodies rituximab, Ibritumomab tiuxetan, and tositumomab, which are all active agents in the treatment of all B cell lymphomas and leukemias.

Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials) include AME-133v (Applied Molecular Evolution), Ocrelizumab (Roche) especially for rheumatoid arthritis, Ofatumumab (Genmab), TRU-015 (Trubion) and IMMU-106 (Immunomedics).[6]

FMC7 appears to be a conformational variant.[7]

References

  1. ^ Tedder TF, Streuli M, Schlossman SF, Saito H (Mar 1988). "Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes". Proc Natl Acad Sci U S A 85 (1): 208-12. PMID 2448768.  
  2. ^ a b "Entrez Gene: MS4A1 membrane-spanning 4-domains, subfamily A, member 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=931.  
  3. ^ The biology of CD20 and its potential as a target for mAb therapy.[1]
  4. ^ Bona, Constantin; Francisco A. Bonilla (1996). "5". Textbook of Immunology. Martin Soohoo (2 ed.). CRC Press. p. 102. ISBN 9783718605965.  
  5. ^ Fang D, Nguyen TK, Leishear K, et al. (2005). "A tumorigenic subpopulation with stem cell properties in melanomas". Cancer Res. 65 (20): 9328–37. doi:10.1158/0008-5472.CAN-05-1343. PMID 16230395.  
  6. ^ Note: information included in this article only found in table present in print version of article. K. John Morrow Jr (2008-06-15). "Methods for Maximizing Antibody Yields". Genetic Engineering & Biotechnology News (Mary Ann Liebert, Inc.): p. 36. http://www.genengnews.com/articles/chitem.aspx?aid=2514. Retrieved 2008-07-06.  
  7. ^ Polyak MJ, Ayer LM, Szczepek AJ, Deans JP (2003). "A cholesterol-dependent CD20 epitope detected by the FMC7 antibody". Leukemia 17 (7): 1384–9. doi:10.1038/sj.leu.2402978. PMID 12835728.  

Further reading

  • Macardle PJ, Nicholson IC (2003). "CD20.". J. Biol. Regul. Homeost. Agents 16 (2): 136–8. PMID 12144126.  
  • Tamayose K, Sato N, Ando J, et al. (2002). "CD3-negative, CD20-positive T-cell prolymphocytic leukemia: case report and review of the literature.". Am. J. Hematol. 71 (4): 331–5. doi:10.1002/ajh.10224. PMID 12447967.  
  • Küster H, Zhang L, Brini AT, et al. (1992). "The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor.". J. Biol. Chem. 267 (18): 12782–7. PMID 1535625.  
  • Einfeld DA, Brown JP, Valentine MA, et al. (1988). "Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains.". EMBO J. 7 (3): 711–7. PMID 2456210.  
  • Tedder TF, Disteche CM, Louie E, et al. (1989). "The gene that encodes the human CD20 (B1) differentiation antigen is located on chromosome 11 near the t(11;14)(q13;q32) translocation site.". J. Immunol. 142 (7): 2555–9. PMID 2466898.  
  • Tedder TF, Klejman G, Schlossman SF, Saito H (1989). "Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1).". J. Immunol. 142 (7): 2560–8. PMID 2466899.  
  • Loken MR, Shah VO, Dattilio KL, Civin CI (1987). "Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development.". Blood 70 (5): 1316–24. PMID 3117132.  
  • Stamenkovic I, Seed B (1988). "Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein.". J. Exp. Med. 167 (6): 1975–80. doi:10.1084/jem.167.6.1975. PMID 3260267.  
  • Bofill M, Janossy G, Janossa M, et al. (1985). "Human B cell development. II. Subpopulations in the human fetus.". J. Immunol. 134 (3): 1531–8. PMID 3871452.  
  • Deans JP, Kalt L, Ledbetter JA, et al. (1995). "Association of 75/80-kDa phosphoproteins and the tyrosine kinases Lyn, Fyn, and Lck with the B cell molecule CD20. Evidence against involvement of the cytoplasmic regions of CD20.". J. Biol. Chem. 270 (38): 22632–8. PMID 7545683.  
  • Valentine MA, Licciardi KA, Clark EA, et al. (1993). "Insulin regulates serine/threonine phosphorylation in activated human B lymphocytes.". J. Immunol. 150 (1): 96–105. PMID 7678037.  
  • Bubien JK, Zhou LJ, Bell PD, et al. (1993). "Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes.". J. Cell Biol. 121 (5): 1121–32. doi:10.1083/jcb.121.5.1121. PMID 7684739.  
  • Shirakawa T, Li A, Dubowitz M, et al. (1994). "Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor.". Nat. Genet. 7 (2): 125–9. doi:10.1038/ng0694-125. PMID 7920628.  
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.  
  • Szepetowski P, Perucca-Lostanlen D, Gaudray P (1993). "Mapping genes according to their amplification status in tumor cells: contribution to the map of 11q13.". Genomics 16 (3): 745–50. doi:10.1006/geno.1993.1257. PMID 8325649.  
  • Algino KM, Thomason RW, King DE, et al. (1996). "CD20 (pan-B cell antigen) expression on bone marrow-derived T cells.". Am. J. Clin. Pathol. 106 (1): 78–81. PMID 8701937.  
  • Szöllósi J, Horejsí V, Bene L, et al. (1996). "Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY.". J. Immunol. 157 (7): 2939–46. PMID 8816400.  
  • Kanzaki M, Lindorfer MA, Garrison JC, Kojima I (1997). "Activation of the calcium-permeable cation channel CD20 by alpha subunits of the Gi protein.". J. Biol. Chem. 272 (23): 14733–9. doi:10.1074/jbc.272.23.14733. PMID 9169438.  
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.  

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