B-cell maturation antigen

2018-10-11T15:28:03Z

212.114.116.234:

{{Infobox_gene}}
{{Infobox protein family
| Symbol = BCMA-Tall_bind
| Name = BCMA TALL-1 binding domain
| image = PDB 1oqd EBI.jpg
| width =
| caption = crystal structure of stall-1 and bcma
| Pfam = PF09257
| Pfam_clan =
| InterPro = IPR015337
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1oqd
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
'''B-cell maturation antigen''' ('''BCMA''' or '''BCM'''), also known as '''tumor necrosis factor receptor superfamily member 17''' ('''TNFRSF17'''), is a [[protein]] that in humans is encoded by the TNFRSF17 [[gene]].

TNFRSF17 is a [[cell surface receptor]] of the [[TNF receptor]] superfamily which recognizes [[B-cell activating factor]] (BAFF).<ref name="pmid1396583">{{cite journal | vauthors = Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A | title = A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma | journal = The EMBO Journal | volume = 11 | issue = 11 | pages = 3897–904 | date = Nov 1992 | pmid = 1396583 | pmc = 556899 | doi = }}</ref><ref name="pmid8165126">{{cite journal | vauthors = Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A | title = The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed | journal = Nucleic Acids Research | volume = 22 | issue = 7 | pages = 1147–54 | date = Apr 1994 | pmid = 8165126 | pmc = 523635 | doi = 10.1093/nar/22.7.1147 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=608| accessdate = }}</ref>

== Function ==
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature [[B lymphocyte]]s, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation.<ref name="entrez" />

== Interactions ==

TNFRSF17 has been shown to [[Protein-protein interaction|interact]] with the B-cell activating factor [[TNFSF13B]].<ref name=pmid12721620>{{cite journal | vauthors = Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan CH, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G | title = Ligand-receptor binding revealed by the TNF family member TALL-1 | journal = Nature | volume = 423 | issue = 6935 | pages = 49–56 | date = May 2003 | pmid = 12721620 | doi = 10.1038/nature01543 }}</ref><ref name=pmid10908663>{{cite journal | vauthors = Shu HB, Johnson H | title = B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 16 | pages = 9156–61 | date = Aug 2000 | pmid = 10908663 | pmc = 16838 | doi = 10.1073/pnas.160213497 }}</ref> A conserved domain at the [[N-terminus]], BCMA TALL-1 binding domain, is required for [[Binding (molecular)|binding]] to the TNFSF13B.<ref name="pmid12721620" />

== Clinical significance - Related Diseases ==

TNFRSF17 is implicated in [[leukemia]], [[lymphoma]]s, and [[multiple myeloma]] <ref>{{cite web|url=http://atlasgeneticsoncology.org/Genes/TNFRSF17ID42616ch16p13.html|title=TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)|website=atlasgeneticsoncology.org}}</ref> (see the "Mitelman Database" <ref>{{cite web|url=http://cgap.nci.nih.gov/Chromosomes/Mitelman|title=Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer}}</ref> and the [[Atlas of Genetics and Cytogenetics in Oncology and Haematology]],<ref>{{cite web|url=http://Atlasgeneticsoncology.org|title=Atlas of Genetics and Cytogenetics in Oncology and Haematology|work=atlasgeneticsoncology.org}}</ref>).

== As a drug target ==
In 2017, a phase 1 [[clinical trial]] employed a [[CAR-T therapy]] that targeted BCMA02 in [[multiple myeloma]].<ref>{{Cite news|url=https://clinicaltrials.gov/ct2/show/NCT02658929|title=Study of bb2121 in Multiple Myeloma - Full Text View - ClinicalTrials.gov|access-date=2017-12-12|language=en}}</ref> Side-effects seen include [[cytokine release syndrome]] and mild neurotoxicity.<ref>[https://www.healio.com/hematology-oncology/myeloma/news/online/%7Bfd4d6216-c366-4537-b6b1-436e93e8fae9%7D/car-t-cell-therapy-bb2121-shows-promising-efficacy-for-multiple-myeloma ''CAR T-cell therapy bb2121 shows promising efficacy for multiple myeloma'']</ref>

An [[antibody-drug conjugate]] [[GSK2857916]] is in early clinical trials.<ref>[https://clinicaltrials.gov/ct2/show/NCT02064387 ''Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916'']</ref><ref name=BF>[http://www.cancernetwork.com/ash-multiple-myeloma/early-promise-experimental-antibody-drug-conjugate-multiple-myeloma ''Early Promise for Experimental Antibody-Drug Conjugate in Multiple Myeloma'']</ref> Side effects are expected to include corneal toxicity.<ref name=BF/>

== References ==
{{reflist}}

==External links==
* {{UCSC gene info|TNFRSF17}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Treml LS, Crowley JE, Cancro MP | title = BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 297–304 | date = Oct 2006 | pmid = 16919470 | doi = 10.1016/j.smim.2006.07.001 }}
* {{cite journal | vauthors = Mackay F, Leung H | title = The role of the BAFF/APRIL system on T cell function | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 284–9 | date = Oct 2006 | pmid = 16931039 | doi = 10.1016/j.smim.2006.04.005 }}
* {{cite journal | vauthors = Gras MP, Laâbi Y, Linares-Cruz G, Blondel MO, Rigaut JP, Brouet JC, Leca G, Haguenauer-Tsapis R, Tsapis A | title = BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes | journal = [[International Immunology]] | volume = 7 | issue = 7 | pages = 1093–106 | date = Jul 1995 | pmid = 8527407 | doi = 10.1093/intimm/7.7.1093 }}
* {{cite journal | vauthors = Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD | title = Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q | journal = Genomics | volume = 60 | issue = 3 | pages = 295–308 | date = Sep 1999 | pmid = 10493829 | doi = 10.1006/geno.1999.5927 }}
* {{cite journal | vauthors = Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH | title = TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease | journal = Nature | volume = 404 | issue = 6781 | pages = 995–9 | date = Apr 2000 | pmid = 10801128 | doi = 10.1038/35010115 }}
* {{cite journal | vauthors = Hatzoglou A, Roussel J, Bourgeade MF, Rogier E, Madry C, Inoue J, Devergne O, Tsapis A | title = TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase | journal = Journal of Immunology | volume = 165 | issue = 3 | pages = 1322–30 | date = Aug 2000 | pmid = 10903733 | doi = 10.4049/jimmunol.165.3.1322 }}
* {{cite journal | vauthors = Shu HB, Johnson H | title = B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 16 | pages = 9156–61 | date = Aug 2000 | pmid = 10908663 | pmc = 16838 | doi = 10.1073/pnas.160213497 }}
* {{cite journal | vauthors = Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE | title = APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity | journal = Nature Immunology | volume = 1 | issue = 3 | pages = 252–6 | date = Sep 2000 | pmid = 10973284 | doi = 10.1038/79802 }}
* {{cite journal | vauthors = Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K | title = Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis | journal = Genes and Immunity | volume = 2 | issue = 5 | pages = 276–9 | date = Aug 2001 | pmid = 11528522 | doi = 10.1038/sj.gene.6363770 }}
* {{cite journal | vauthors = Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF | title = Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival | journal = Blood | volume = 103 | issue = 2 | pages = 689–94 | date = Jan 2004 | pmid = 14512299 | doi = 10.1182/blood-2003-06-2043 }}
* {{cite journal | vauthors = Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA | title = Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding | journal = The Journal of Biological Chemistry | volume = 280 | issue = 8 | pages = 7218–27 | date = Feb 2005 | pmid = 15542592 | doi = 10.1074/jbc.M411714200 }}
* {{cite journal | vauthors = Bellucci R, Alyea EP, Chiaretti S, Wu CJ, Zorn E, Weller E, Wu B, Canning C, Schlossman R, Munshi NC, Anderson KC, Ritz J | title = Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor | journal = Blood | volume = 105 | issue = 10 | pages = 3945–50 | date = May 2005 | pmid = 15692072 | pmc = 1895080 | doi = 10.1182/blood-2004-11-4463 }}
* {{cite journal | vauthors = Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP | title = Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation | journal = Cell Death and Differentiation | volume = 12 | issue = 6 | pages = 637–48 | date = Jun 2005 | pmid = 15846369 | doi = 10.1038/sj.cdd.4401647 }}
* {{cite journal | vauthors = Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E, Qiao X, Santini P, Hyjek E, Lee JW, Cesarman E, Chadburn A, Knowles DM, Cerutti A | title = Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL | journal = Blood | volume = 109 | issue = 2 | pages = 729–39 | date = Jan 2007 | pmid = 16960154 | pmc = 1785096 | doi = 10.1182/blood-2006-04-015958 }}
* {{cite journal | vauthors = Smirnova AS, Andrade-Oliveira V, Gerbase-DeLima M | title = Identification of new splice variants of the genes BAFF and BCMA | journal = Molecular Immunology | volume = 45 | issue = 4 | pages = 1179–1183 | date = Feb 2008 | pmid = 17825416 | doi = 10.1016/j.molimm.2007.07.028 }}
{{refend}}

{{NLM content}}
{{PDB Gallery|geneid=608}}
{{Clusters of differentiation}}
{{Tumor necrosis factor receptor superfamily}}
{{Cytokine receptor modulators}}
{{InterPro content|IPR015337}}

[[Category:Protein domains]]
[[Category:Clusters of differentiation]]
[[Category:TNF receptor family]]

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B-cell maturation antigen