Transmembrane activator and CAML interactor

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TNFRSF13B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFRSF13B, CD267, CVID, CVID2, RYZN, TACI, TNFRSF14B, IGAD2, tumor necrosis factor receptor superfamily member 13B, TNF receptor superfamily member 13B
External IDsOMIM: 604907 MGI: 1889411 HomoloGene: 49320 GeneCards: TNFRSF13B
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012452

NM_021349

RefSeq (protein)

NP_036584

NP_067324

Location (UCSC)Chr 17: 16.93 – 16.97 MbChr 11: 61.02 – 61.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene.

TNFRSF13B is a transmembrane protein of the TNF receptor superfamily found predominantly on the surface of B cells, which are an important part of the immune system.[5] TACI recognizes three ligands: APRIL, BAFF and CAML.

Function

TACI is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It was originally discovered because of its ability to interact with calcium-modulator and cyclophilin ligand (CAML). TACI was later found to play a crucial role in humoral immunity by interacting with two members of the TNF family: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL).[6] These proteins signal through TACI inducing activation of several transcription factors including NFAT, AP-1, and NF-kappa-B which then modulate cellular activities. Defects in the function of TACI can lead to immune system diseases and has shown to cause fatal autoimmunity in mice.[7]

TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.[citation needed]

Clinical significance

TACI mutations are associated with immunodeficiency in humans, as a significant proportion of common variable immunodeficiency (CVID) patients have TACI mutations.[citation needed] People with this condition produce abnormally low amounts of antibodies, which are needed for protection against infections.

In humans, the gene encoding this protein is located within the Smith–Magenis syndrome region on chromosome 17.[5]

TACI is currently being targeted for autoimmunity and B cell malignancies via atacicept, a recombinant fusion protein that binds the TACI ligands BAFF and APRIL.[8]

Interactions

TNFRSF13B has been shown to interact with B-cell activating factor,[9][10] TRAF6,[10] TRAF5,[10] TNFSF13,[6] TRAF2[10] and CAMLG.[10][11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000240505 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000010142 - 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. ^ a b "Entrez Gene: TNFRSF13B tumor necrosis factor receptor superfamily, member 13B".
  6. ^ a b Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP (November 2000). "Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS". The Journal of Biological Chemistry. 275 (45): 35478–85. doi:10.1074/jbc.M005224200. PMID 10956646.
  7. ^ Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS (February 2003). "Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor". Immunity. 18 (2): 279–88. doi:10.1016/s1074-7613(03)00025-6. PMID 12594954.
  8. ^ Cogollo E, Cogollo E, Silva MA, Isenberg D (March 2015). "Profile of atacicept and its potential in the treatment of systemic lupus erythematosus". Drug Design, Development and Therapy. 9: 1331–9. doi:10.2147/dddt.s71276. PMC 4357613. PMID 25834391.
  9. ^ Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM (July 2000). "Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity". Nature Immunology. 1 (1): 37–41. doi:10.1038/76889. PMID 10881172. S2CID 22957179.
  10. ^ a b c d e Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H (July 2000). "TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation". The Journal of Experimental Medicine. 192 (1): 137–43. doi:10.1084/jem.192.1.137. PMC 1887716. PMID 10880535.
  11. ^ von Bülow GU, Bram RJ (October 1997). "NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily". Science. 278 (5335): 138–41. doi:10.1126/science.278.5335.138. PMID 9311921.

Further reading

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