Biology:Transmembrane activator and CAML interactor

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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. 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). 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.

TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.

Clinical significance

TACI mutations are associated with immunodeficiency in humans, as a significant proportion of common variable immunodeficiency (CVID) patients have TACI mutations. 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.

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.

Interactions

TNFRSF13B has been shown to interact with B-cell activating factor, TRAF6, TRAF5, TNFSF13, TRAF2 and CAMLG.

Further reading

• "BAFF, APRIL and their receptors: structure, function and signaling". Seminars in Immunology 18 (5): 263–75. October 2006. doi:10.1016/j.smim.2006.04.006. PMID 16914324. https://serval.unil.ch/resource/serval:BIB_89872BC6E950.P001/REF.pdf. 
• "BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells". Seminars in Immunology 18 (5): 297–304. October 2006. doi:10.1016/j.smim.2006.07.001. PMID 16919470. 
• "The role of the BAFF/APRIL system on T cell function". Seminars in Immunology 18 (5): 284–9. October 2006. doi:10.1016/j.smim.2006.04.005. PMID 16931039. 
• "To switch or not to switch--the opposing roles of TACI in terminal B cell differentiation". European Journal of Immunology 37 (1): 17–20. January 2007. doi:10.1002/eji.200636914. PMID 17171762. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily". Science 278 (5335): 138–41. October 1997. doi:10.1126/science.278.5335.138. PMID 9311921. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease". Nature 404 (6781): 995–9. April 2000. doi:10.1038/35010115. PMID 10801128. Bibcode: 2000Natur.404..995G. 
• "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. July 2000. doi:10.1084/jem.192.1.137. PMID 10880535. 
• "Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor". Immunity 18 (2): 279–88. February 2003. doi:10.1016/s1074-7613(03)00025-6. PMID 12594954. 
• "Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI". Current Biology 10 (13): 785–8. June 2000. doi:10.1016/S0960-9822(00)00566-2. PMID 10898980. 
• "Molecular cloning and functional characterization of murine transmembrane activator and CAML interactor (TACI) with chromosomal localization in human and mouse". Mammalian Genome 11 (8): 628–32. August 2000. doi:10.1007/s003350010125. PMID 10920230. 
• "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. November 2000. doi:10.1074/jbc.M005224200. PMID 10956646. 
• "APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity". Nature Immunology 1 (3): 252–6. September 2000. doi:10.1038/79802. PMID 10973284. 
• "Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival". Blood 103 (2): 689–94. January 2004. doi:10.1182/blood-2003-06-2043. PMID 14512299. 
• "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. February 2005. doi:10.1074/jbc.M411714200. PMID 15542592. 
• "The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature". Blood 106 (3): 1021–30. August 2005. doi:10.1182/blood-2004-11-4512. PMID 15827134. 
• "TACI is mutant in common variable immunodeficiency and IgA deficiency". Nature Genetics 37 (8): 829–34. August 2005. doi:10.1038/ng1601. PMID 16007086. 

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