Transmembrane activator and CAML interactor

TNFRSF13B
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1XU1, 1XUT
Identifiers
Aliases	TNFRSF13B, CD267, CVID, CVID2, RYZN, TACI, TNFRSF14B, IGAD2, tumor necrosis factor receptor superfamily member 13B, TNF receptor superfamily member 13B
External IDs	OMIM: 604907; MGI: 1889411; HomoloGene: 49320; GeneCards: TNFRSF13B; OMA:TNFRSF13B - orthologs
Gene location (Human)
Chr.	Chromosome 17 (human)
End	16,972,118 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	61,040,198 bp
RNA expression pattern
	Top expressed in
	spleen; ; apex of heart; ; lymph node; ; tendon of biceps brachii; ; muscle of thigh; ; bone marrow cells; ; gastrocnemius muscle; ; cecum; ; appendix; ; parotid gland;
	Top expressed in
	spleen; ; mesenteric lymph nodes; ; bone marrow; ; blood; ; thymus; ; stroma of bone marrow; ; granulocyte; ; tibiofemoral joint; ; subcutaneous adipose tissue; ; embryo;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding; signaling receptor activity;
Cellular component	integral component of membrane; integral component of plasma membrane; membrane; plasma membrane;
Biological process	cell surface receptor signaling pathway; tumor necrosis factor-mediated signaling pathway; adaptive immune response; immune system process; B cell homeostasis; hematopoietic progenitor cell differentiation; negative regulation of B cell proliferation;
	Sources:Amigo / QuickGO
Orthologs
	23495
	57916
	ENSG00000240505
	ENSMUSG00000010142
	O14836
	Q9ET35
	NM_012452
	NM_021349
	NP_036584
	NP_067324
	Wikidata
View/Edit Human	View/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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000240505 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000010142 – 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.
^ ^a ^b "Entrez Gene: TNFRSF13B tumor necrosis factor receptor superfamily, member 13B".
^ ^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.
^ 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.
^ 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.
^ 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.
^ ^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.
^ 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.

Bossen C, Schneider P (October 2006). "BAFF, APRIL and their receptors: structure, function and signaling" (PDF). Seminars in Immunology. 18 (5): 263–75. doi:10.1016/j.smim.2006.04.006. PMID 16914324.
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.
Salzer U, Jennings S, Grimbacher B (January 2007). "To switch or not to switch--the opposing roles of TACI in terminal B cell differentiation". European Journal of Immunology. 37 (1): 17–20. doi:10.1002/eji.200636914. PMID 17171762. S2CID 321714.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
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.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH (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.
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.
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.
Marsters SA, Yan M, Pitti RM, Haas PE, Dixit VM, Ashkenazi A (June 2000). "Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI". Current Biology. 10 (13): 785–8. Bibcode:2000CBio...10..785M. doi:10.1016/S0960-9822(00)00566-2. PMID 10898980. S2CID 2054515.
von Bülow GU, Russell H, Copeland NG, Gilbert DJ, Jenkins NA, Bram RJ (August 2000). "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. doi:10.1007/s003350010125. PMID 10920230. S2CID 30311754.
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.
Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE (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.
Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF (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, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA (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.
Moreaux J, Cremer FW, Reme T, Raab M, Mahtouk K, Kaukel P, Pantesco V, De Vos J, Jourdan E, Jauch A, Legouffe E, Moos M, Fiol G, Goldschmidt H, Rossi JF, Hose D, Klein B (August 2005). "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. doi:10.1182/blood-2004-11-4512. PMC 2408610. PMID 15827134.
Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS (August 2005). "TACI is mutant in common variable immunodeficiency and IgA deficiency". Nature Genetics. 37 (8): 829–34. doi:10.1038/ng1601. PMID 16007086. S2CID 20026177.

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000240505 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[entrez-5] "Entrez Gene: TNFRSF13B tumor necrosis factor receptor superfamily, member 13B".

[pmid10956646-6] 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.

[Xia_2000-10] 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.

[von_Bülow_1997-11] 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.

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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

Transmembrane activator and CAML interactor

Function

Clinical significance

Interactions

References

Further reading

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