B-cell maturation antigen

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TNFRSF17
Protein TNFRSF17 PDB 1oqd.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TNFRSF17, BCM, BCMA, CD269, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, TNF receptor superfamily member 17
External IDs MGI: 1343050 HomoloGene: 920 GeneCards: TNFRSF17
Gene location (Human)
Chromosome 16 (human)
Chr. Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for TNFRSF17
Genomic location for TNFRSF17
Band 16p13.13 Start 11,965,107 bp[1]
End 11,968,068 bp[1]
RNA expression pattern
PBB GE TNFRSF17 206641 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001192

NM_011608

RefSeq (protein)

NP_001183

NP_035738

Location (UCSC) Chr 16: 11.97 – 11.97 Mb Chr 16: 11.31 – 11.32 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
BCMA TALL-1 binding domain
PDB 1oqd EBI.jpg
crystal structure of stall-1 and bcma
Identifiers
Symbol BCMA-Tall_bind
Pfam PF09257
InterPro IPR015337
SCOP 1oqd
SUPERFAMILY 1oqd

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[edit]

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[edit]

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[edit]

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[edit]

In 2017, a phase 1 clinical trial employed a CAR-T therapy that targeted BCMA02 in multiple myeloma with a drug labeled bb2121.[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[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000048462 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022496 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  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. PMC 556899Freely accessible. 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 523635Freely accessible. PMID 8165126. 
  7. ^ a b "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17". 
  8. ^ a b 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 16838Freely accessible. 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. ^ a b Early Promise for Experimental Antibody-Drug Conjugate in Multiple Myeloma

External links[edit]

Further reading[edit]

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