B-cell maturation antigen

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
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFRSF17, BCM, BCMA, CD269, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, TNF receptor superfamily member 17
External IDsOMIM: 109545 MGI: 1343050 HomoloGene: 920 GeneCards: TNFRSF17
Gene location (Human)
Chr.Chromosome 16 (human)[1]
Band16p13.13Start11,965,210 bp[1]
End11,968,068 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

608

21935

Ensembl

ENSG00000048462

ENSMUSG00000022496

UniProt

Q02223

O88472

RefSeq (mRNA)

NM_001192

NM_011608

RefSeq (protein)

NP_001183

NP_035738

Location (UCSC)Chr 16: 11.97 – 11.97 MbChr 16: 11.31 – 11.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
BCMA TALL-1 binding domain
crystal structure of stall-1 and bcma
Identifiers
SymbolBCMA-Tall_bind
PfamPF09257
InterProIPR015337
SCOPe1oqd / SUPFAM

TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF).[5][6][7]

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, 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.[7]

Interactions

TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B.[8][9] A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.[8]

Clinical significance - Related Diseases

TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma [10] (see the "Mitelman Database" [11] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[12]).

As a drug target

In 2017, a phase 1 clinical trial employed a CAR-T therapy that targeted BCMA02 in multiple myeloma.[13] Side-effects seen include cytokine release syndrome and mild neurotoxicity.[14]

An antibody-drug conjugate GSK2857916 is in early clinical trials.[15][16] Side effects are expected to include corneal toxicity.[16]

References
  1. GRCh38: Ensembl release 89: ENSG00000048462 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022496 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (Nov 1992). "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". The EMBO Journal. 11 (11): 3897–904. doi:10.1002/j.1460-2075.1992.tb05482.x. PMC 556899. PMID 1396583.
  6. Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A (Apr 1994). "The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed". Nucleic Acids Research. 22 (7): 1147–54. doi:10.1093/nar/22.7.1147. PMC 523635. PMID 8165126.
  7. "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".
  8. Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan CH, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature. 423 (6935): 49–56. doi:10.1038/nature01543. PMID 12721620.
  9. Shu HB, Johnson H (Aug 2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (16): 9156–61. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
  10. "TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)". atlasgeneticsoncology.org.
  11. "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer".
  12. "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org.
  13. "Study of bb2121 in Multiple Myeloma - Full Text View - ClinicalTrials.gov". Retrieved 2017-12-12.
  14. CAR T-cell therapy bb2121 shows promising efficacy for multiple myeloma
  15. Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916
  16. Early Promise for Experimental Antibody-Drug Conjugate in Multiple Myeloma

Further reading
  • Treml LS, Crowley JE, Cancro MP (Oct 2006). "BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells". Seminars in Immunology. 18 (5): 297–304. doi:10.1016/j.smim.2006.07.001. PMID 16919470.
  • Mackay F, Leung H (Oct 2006). "The role of the BAFF/APRIL system on T cell function". Seminars in Immunology. 18 (5): 284–9. doi:10.1016/j.smim.2006.04.005. PMID 16931039.
  • Gras MP, Laâbi Y, Linares-Cruz G, Blondel MO, Rigaut JP, Brouet JC, Leca G, Haguenauer-Tsapis R, Tsapis A (Jul 1995). "BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes". International Immunology. 7 (7): 1093–106. doi:10.1093/intimm/7.7.1093. PMID 8527407.
  • 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 (Sep 1999). "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics. 60 (3): 295–308. doi:10.1006/geno.1999.5927. PMID 10493829.
  • 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 (Apr 2000). "TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease". Nature. 404 (6781): 995–9. doi:10.1038/35010115. PMID 10801128.
  • Hatzoglou A, Roussel J, Bourgeade MF, Rogier E, Madry C, Inoue J, Devergne O, Tsapis A (Aug 2000). "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 of Immunology. 165 (3): 1322–30. doi:10.4049/jimmunol.165.3.1322. PMID 10903733.
  • Shu HB, Johnson H (Aug 2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (16): 9156–61. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
  • 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 (Sep 2000). "APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity". Nature Immunology. 1 (3): 252–6. doi:10.1038/79802. PMID 10973284.
  • Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K (Aug 2001). "Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis". Genes and Immunity. 2 (5): 276–9. doi:10.1038/sj.gene.6363770. PMID 11528522.
  • Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF (Jan 2004). "Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival". Blood. 103 (2): 689–94. doi:10.1182/blood-2003-06-2043. PMID 14512299.
  • Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA (Feb 2005). "Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding". The Journal of Biological Chemistry. 280 (8): 7218–27. doi:10.1074/jbc.M411714200. PMID 15542592.
  • Bellucci R, Alyea EP, Chiaretti S, Wu CJ, Zorn E, Weller E, Wu B, Canning C, Schlossman R, Munshi NC, Anderson KC, Ritz J (May 2005). "Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor". Blood. 105 (10): 3945–50. doi:10.1182/blood-2004-11-4463. PMC 1895080. PMID 15692072.
  • Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP (Jun 2005). "Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation". Cell Death and Differentiation. 12 (6): 637–48. doi:10.1038/sj.cdd.4401647. PMID 15846369.
  • 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 (Jan 2007). "Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL". Blood. 109 (2): 729–39. doi:10.1182/blood-2006-04-015958. PMC 1785096. PMID 16960154.
  • Smirnova AS, Andrade-Oliveira V, Gerbase-DeLima M (Feb 2008). "Identification of new splice variants of the genes BAFF and BCMA". Molecular Immunology. 45 (4): 1179–1183. doi:10.1016/j.molimm.2007.07.028. PMID 17825416.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article incorporates text from the public domain Pfam and InterPro: IPR015337
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