CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells.
Membrane-spanning 4-domains, subfamily A, member 1, also known as MS4A1, is a human gene.[cite web | title = Entrez Gene: MS4A1 membrane-spanning 4-domains, subfamily A, member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=931| accessdate = ] ] PBB_Summary
section_title =
summary_text = 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.[cite web | title = Entrez Gene: MS4A1 membrane-spanning 4-domains, subfamily A, member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=931| accessdate = ] ]
Function
The protein has no known natural ligand[The biology of CD20 and its potential as a target for mAb therapy. [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=PubMed&TermToSearch=15564720] ] and its function is unclear. It is suspected that it acts as a calcium channel in the cell membrane. It is also found on B-cell lymphomas, hairy cell leukemia, and B-cell chronic lymphocytic leukemia.It is also found on skin/melanoma cancer stem cells.][cite journal |author=Fang D, Nguyen TK, Leishear K, "et al" |title=A tumorigenic subpopulation with stem cell properties in melanomas |journal=Cancer Res. |volume=65 |issue=20 |pages=9328–37 |year=2005 |pmid=16230395 |doi=10.1158/0008-5472.CAN-05-1343] ]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 antibody therapeutics under development (phase II or III clinical trials) include AME-133v (Applied Molecular Evolution), Ocrelizumab (Roche), Ofatumumab (Genmab), TRU-015 (Trubion) and IMMU-106 (Immunomedics). ["Note: information included in this article only found in table present in print version of article." cite news | author=K. John Morrow Jr
title=Methods for Maximizing Antibody Yields | url=http://www.genengnews.com/articles/chitem.aspx?aid=2514
work=Genetic Engineering & Biotechnology News | publisher=Mary Ann Liebert, Inc. | page=36 | date=2008-06-15
accessdate=2008-07-06 | quote= ]
FMC7 appears to be a conformational variant.[cite journal |author=Polyak MJ, Ayer LM, Szczepek AJ, Deans JP |title=A cholesterol-dependent CD20 epitope detected by the FMC7 antibody |journal=Leukemia |volume=17 |issue=7 |pages=1384–9 |year=2003 |pmid=12835728 |doi=10.1038/sj.leu.2402978] ]References
Further reading
PBB_Further_reading
citations =
*cite journal | author=Macardle PJ, Nicholson IC |title=CD20. |journal=J. Biol. Regul. Homeost. Agents |volume=16 |issue= 2 |pages= 136–8 |year= 2003 |pmid= 12144126 |doi=
*cite journal | author=Tamayose K, Sato N, Ando J, "et al." |title=CD3-negative, CD20-positive T-cell prolymphocytic leukemia: case report and review of the literature. |journal=Am. J. Hematol. |volume=71 |issue= 4 |pages= 331–5 |year= 2002 |pmid= 12447967 |doi= 10.1002/ajh.10224
*cite journal | author=Küster H, Zhang L, Brini AT, "et al." |title=The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor. |journal=J. Biol. Chem. |volume=267 |issue= 18 |pages= 12782–7 |year= 1992 |pmid= 1535625 |doi=
*cite journal | author=Tedder TF, Streuli M, Schlossman SF, Saito H |title=Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 1 |pages= 208–12 |year= 1988 |pmid= 2448768 |doi=
*cite journal | author=Einfeld DA, Brown JP, Valentine MA, "et al." |title=Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains. |journal=EMBO J. |volume=7 |issue= 3 |pages= 711–7 |year= 1988 |pmid= 2456210 |doi=
*cite journal | author=Tedder TF, Disteche CM, Louie E, "et al." |title=The gene that encodes the human CD20 (B1) differentiation antigen is located on chromosome 11 near the t(11;14)(q13;q32) translocation site. |journal=J. Immunol. |volume=142 |issue= 7 |pages= 2555–9 |year= 1989 |pmid= 2466898 |doi=
*cite journal | author=Tedder TF, Klejman G, Schlossman SF, Saito H |title=Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1). |journal=J. Immunol. |volume=142 |issue= 7 |pages= 2560–8 |year= 1989 |pmid= 2466899 |doi=
*cite journal | author=Loken MR, Shah VO, Dattilio KL, Civin CI |title=Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development. |journal=Blood |volume=70 |issue= 5 |pages= 1316–24 |year= 1987 |pmid= 3117132 |doi=
*cite journal | author=Stamenkovic I, Seed B |title=Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein. |journal=J. Exp. Med. |volume=167 |issue= 6 |pages= 1975–80 |year= 1988 |pmid= 3260267 |doi=
*cite journal | author=Bofill M, Janossy G, Janossa M, "et al." |title=Human B cell development. II. Subpopulations in the human fetus. |journal=J. Immunol. |volume=134 |issue= 3 |pages= 1531–8 |year= 1985 |pmid= 3871452 |doi=
*cite journal | author=Deans JP, Kalt L, Ledbetter JA, "et al." |title=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. |journal=J. Biol. Chem. |volume=270 |issue= 38 |pages= 22632–8 |year= 1995 |pmid= 7545683 |doi=
*cite journal | author=Valentine MA, Licciardi KA, Clark EA, "et al." |title=Insulin regulates serine/threonine phosphorylation in activated human B lymphocytes. |journal=J. Immunol. |volume=150 |issue= 1 |pages= 96–105 |year= 1993 |pmid= 7678037 |doi=
*cite journal | author=Bubien JK, Zhou LJ, Bell PD, "et al." |title=Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes. |journal=J. Cell Biol. |volume=121 |issue= 5 |pages= 1121–32 |year= 1993 |pmid= 7684739 |doi=
*cite journal | author=Shirakawa T, Li A, Dubowitz M, "et al." |title=Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor. |journal=Nat. Genet. |volume=7 |issue= 2 |pages= 125–9 |year= 1994 |pmid= 7920628 |doi= 10.1038/ng0694-125
*cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=
*cite journal | author=Szepetowski P, Perucca-Lostanlen D, Gaudray P |title=Mapping genes according to their amplification status in tumor cells: contribution to the map of 11q13. |journal=Genomics |volume=16 |issue= 3 |pages= 745–50 |year= 1993 |pmid= 8325649 |doi=
*cite journal | author=Algino KM, Thomason RW, King DE, "et al." |title=CD20 (pan-B cell antigen) expression on bone marrow-derived T cells. |journal=Am. J. Clin. Pathol. |volume=106 |issue= 1 |pages= 78–81 |year= 1996 |pmid= 8701937 |doi=
*cite journal | author=Szöllósi J, Horejsí V, Bene L, "et al." |title=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. |journal=J. Immunol. |volume=157 |issue= 7 |pages= 2939–46 |year= 1996 |pmid= 8816400 |doi=
*cite journal | author=Kanzaki M, Lindorfer MA, Garrison JC, Kojima I |title=Activation of the calcium-permeable cation channel CD20 by alpha subunits of the Gi protein. |journal=J. Biol. Chem. |volume=272 |issue= 23 |pages= 14733–9 |year= 1997 |pmid= 9169438 |doi=
*cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, "et al." |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=
External links
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* representations of the shape are found [http://www.rheuma-online.de/medikamente/rituximab-mabthera/detail/wirkmechanismus.html here] and more detail [http://bloodjournal.hematologylibrary.org/cgi/content/full/104/9/2635/FIG1 here]
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