B-cell maturation antigen

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

BCMA TALL-1 binding domain
BCMA TALL-1 binding domain
	crystal structure of stall-1 and bcma
Identifiers
Symbol	BCMA-Tall_bind
Pfam	PF09257
InterPro	IPR015337
SCOP2	1oqd / SCOPe / SUPFAM
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

TNFRSF17
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1OQD, 1XU2, 2KN1, 4ZFO
Identifiers
Aliases	TNFRSF17, BCM, BCMA, CD269, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, TNF receptor superfamily member 17
External IDs	OMIM: 109545; MGI: 1343050; HomoloGene: 920; GeneCards: TNFRSF17; OMA:TNFRSF17 - orthologs
Gene location (Human)
Chr.	Chromosome 16 (human)
End	11,968,068 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	11,137,938 bp
RNA expression pattern
	Top expressed in
	rectum; ; mucosa of transverse colon; ; jejunal mucosa; ; mucosa of sigmoid colon; ; testicle; ; lymph node; ; epithelium of nasopharynx; ; appendix; ; spleen; ; duodenum;
	Top expressed in
	blastocyst; ; morula; ; duodenum; ; jejunum; ; spleen; ; lip; ; thymus; ; secondary oocyte; ; colon; ; ileum;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	signaling receptor activity;
Cellular component	endomembrane system; plasma membrane; membrane; integral component of membrane;
Biological process	multicellular organism development; tumor necrosis factor-mediated signaling pathway; lymphocyte homeostasis; cell population proliferation; immune system process; adaptive immune response; signal transduction;
	Sources:Amigo / QuickGO
Orthologs
	608
	21935
	ENSG00000048462
	ENSMUSG00000022496
	Q02223
	O88472
	NM_001192
	NM_011608
	NP_001183
	NP_035738
	Wikidata
View/Edit Human	View/Edit Mouse

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).^[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

An antibody-drug conjugate GSK2857916 (belantamab mafodotin) demonstrated activity in patients with relapsed/refractory multiple myeloma, previously treated with an immunomodulatory drug, proteosome inhibitor, or who were intolerant/refractory to an anti-CD38 monoclonal antibody. The primary toxicities were keratopathy, thrombocytopenia, and anemia.^[13]

Belantamab mafodotin (GSK2857916) was approved for medical use in the United States in August 2020.^[14]^[15]

A Phase 1b/2 study of CAR-T cell therapy directed against BCMA in myeloma patients refractory to a proteasome inhibitor or immunomodulatory drug, and who had received an anti-CD38 antibody showed a 91% overall response rate. Main toxicities were cytokine release syndrome and cytopenias.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000048462 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022496 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (November 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.
^ Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A (April 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.
^ ^a ^b "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".
^ ^a ^b Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, et al. (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature. 423 (6935): 49–56. Bibcode:2003Natur.423...49L. doi:10.1038/nature01543. PMID 12721620. S2CID 4373708.
^ Shu HB, Johnson H (August 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. Bibcode:2000PNAS...97.9156S. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
^ "TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)". atlasgeneticsoncology.org.
^ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer".
^ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org.
^ Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. (February 2020). "Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study". The Lancet. Oncology. 21 (2): 207–221. doi:10.1016/s1470-2045(19)30788-0. PMID 31859245.
^ "FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma". U.S. Food and Drug Administration (FDA). 5 August 2020. Retrieved 6 August 2020. This article incorporates text from this source, which is in the public domain.
^ "FDA Approves GSK's BLENREP (belantamab mafodotin-blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma" (Press release). GlaxoSmithKline. 6 August 2020. Retrieved 6 August 2020 – via Business Wire.
^ Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, et al. (2019-11-13). "Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM)". Blood. 134 (Supplement_1): 577. doi:10.1182/blood-2019-121731. ISSN 0006-4971.

External links

Human TNFRSF17 genome location and TNFRSF17 gene details page in the UCSC Genome Browser.

Treml LS, Crowley JE, Cancro MP (October 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 (October 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, et al. (July 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, et al. (September 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, et al. (April 2000). "TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease". Nature. 404 (6781): 995–9. Bibcode:2000Natur.404..995G. doi:10.1038/35010115. PMID 10801128. S2CID 4323357.
Hatzoglou A, Roussel J, Bourgeade MF, Rogier E, Madry C, Inoue J, et al. (August 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 (August 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. Bibcode:2000PNAS...97.9156S. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, et al. (September 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. S2CID 6799584.
Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K (August 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, et al. (January 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, et al. (February 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, et al. (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, et al. (June 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, et al. (January 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 (February 2008). "Identification of new splice variants of the genes BAFF and BCMA". Molecular Immunology. 45 (4): 1179–83. 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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000048462 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid1396583-5] Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (November 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.

[pmid8165126-6] Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A (April 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.

[entrez-7] "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".

[pmid12721620-8] Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, et al. (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature. 423 (6935): 49–56. Bibcode:2003Natur.423...49L. doi:10.1038/nature01543. PMID 12721620. S2CID 4373708.

[pmid10908663-9] Shu HB, Johnson H (August 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. Bibcode:2000PNAS...97.9156S. 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] Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. (February 2020). "Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study". The Lancet. Oncology. 21 (2): 207–221. doi:10.1016/s1470-2045(19)30788-0. PMID 31859245.

[FDA_Blenrep-14] "FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma". U.S. Food and Drug Administration (FDA). 5 August 2020. Retrieved 6 August 2020. This article incorporates text from this source, which is in the public domain.

[GSK_PR-15] "FDA Approves GSK's BLENREP (belantamab mafodotin-blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma" (Press release). GlaxoSmithKline. 6 August 2020. Retrieved 6 August 2020 – via Business Wire.

[16] Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, et al. (2019-11-13). "Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM)". Blood. 134 (Supplement_1): 577. doi:10.1182/blood-2019-121731. ISSN 0006-4971.

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v t e Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD327 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350