B-cell maturation antigen

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TNFRSF17
Protein TNFRSF17 PDB 1oqd.png
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)
Chromosome 16 (human)
Chr.Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for TNFRSF17
Genomic location for TNFRSF17
Band16p13.13Start11,965,210 bp[1]
End11,968,068 bp[1]
RNA expression pattern
PBB GE TNFRSF17 206641 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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
PDB 1oqd EBI.jpg
crystal structure of stall-1 and bcma
Identifiers
SymbolBCMA-Tall_bind
PfamPF09257
InterProIPR015337
SCOPe1oqd / SUPFAM

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.[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:". 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. ^ 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 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. ^ 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