TACI Protein (Transmembrane Activator and Calcium Modulator) <table class="infobox infobox-protein">Gene </td>UniProt </td>Molecular Weight </td>Length </td>Cellular Location </td>Protein Family </td>Aliases </td>Ligands </td>
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TACI Protein (Transmembrane Activator and Calcium Modulator) <table class="infobox infobox-protein">Gene </td>UniProt </td>Molecular Weight </td>Length </td>Cellular Location </td>Protein Family </td>Aliases </td>Ligands </td>
:: infobox .infobox-protein
Overview TACI (Transmembrane Activator and Calcium Modulator) , encoded by the TNFRSF13B gene, is a type I transmembrane receptor belonging to the tumor necrosis factor receptor superfamily (TNFRSF). TACI binds two ligands—BAFF (B cell-activating factor, also known as TNFSF13B) and APRIL (A Proliferation-Inducing Ligand, TNFSF13)—to regulate B cell survival, maturation, class switch recombination, and immune homeostasis. TACI is primarily expressed on B cells, particularly class-switched memory B cells and plasma cells. Dysregulated TACI function is implicated in common variable immunodeficiency (CVID), autoimmune disorders, multiple myeloma, and has connections to neuroinflammation in [amyotrophic lateral sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis).
Molecular Structure TACI is a 295-amino acid type I transmembrane protein with:
Signal peptide (1-14 aa) : Secretory signalCysteine-rich domain (CRD1, 15-46 aa) : First ligand-binding domainCRD2 (47-79 aa) : Second ligand-binding domainTransmembrane domain (80-102 aa) : Single pass membrane anchorCytoplasmic tail (103-295 aa) : Contains signaling motifs including:TRAF-binding motifs
NF-κB activation domain
Calcium modulating domain
The extracellular CRDs are characteristic of TNF receptor family members and bind BAFF/APRIL as trimeric ligands.
Ligand Interactions
BAFF (TNFSF13B)
Expression : Produced by myeloid cells, stromal cellsReceptors : TACI, BCMA, BR3Function : B cell survival, maturationAffinity : TACI binds BAFF with moderate affinity (Kd ~ 10⁻⁸ M)APRIL (TNFSF13)
Expression : Produced by immune cells, tumor cellsReceptors : TACI, BCMAFunction : Class switch recombination, plasma cell survivalAffinity : TACI binds APRIL with higher affinityNormal Physiological Function
B Cell Biology TACI regulates multiple aspects of B cell function:
B cell maturation : Promotes transitional B cell survivalClass switch recombination (CSR) : Essential for IgA, IgG, IgE productionPlasma cell survival : Supports long-lived plasma cellsImmune homeostasis : Prevents autoimmunity via B cell regulationSignaling Pathways TACI activates several signaling cascades:
Role in Disease
Common Variable Immunodeficiency (CVID) TACI is one of the most commonly mutated genes in CVID:
Prevalence : ~5-10% of CVID patientsMutation types : Heterozygous and biallelic variantsPhenotype : Antibody deficiency, infectionsIncomplete penetrance : Not all carriers develop CVIDTreatment : Immunoglobulin replacementMultiple Myeloma TACI is a therapeutic target in multiple myeloma:
Expression : MM cells express TACIAutocrine signaling : BAFF/APRIL promote survivalTelitacicept : TACI-Fc fusion protein in trialsCAR T cells : Anti-TACI CAR T cells in developmentAmyotrophic Lateral Sclerosis Connections between TACI and ALS:
Neuroinflammation : B cell involvement in ALSBAFF levels : Elevated in ALS patient serumNeuroimmune interactions : Cross-talk between CNS and immune systemTherapeutic potential : BAFF/APRIL blockadeAutoimmune Disorders TACI dysfunction linked to autoimmunity:
Systemic lupus erythematosus (SLE) Rheumatoid arthritis Multiple sclerosis Therapeutic Targeting
TACI-Fc Fusion Proteins
CAR T Cell Therapy
Anti-TACI CAR T : Targets TACI-expressing cellsBCMA-loss escape : Alternative to BCMA-targetingClinical trials : Showing promise in MMInteraction Network TACI interacts with:
Clinical Significance
Biomarker : TACI expression predicts treatment responseGenetic testing : TNFRSF13B variants in CVID diagnosisTherapeutic target : Multiple drug candidates in developmentAnimal Models
See Also
[TNFRSF13B Gene](/genes/tnfrsf13b) - Gene page for TACI
[BAFF Signaling](/mechanisms/baff-signaling-pathway) - B cell activating factor
[NF-κB Signaling](/mechanisms/nf-kb-signaling-neuroinflammation) - NF-κB pathway
[B Cells](/cell-types/b-lymphocytes) - B lymphocyte biology
[Multiple Myeloma](/diseases/multiple-myeloma) - Plasma cell malignancy
[ALS](/diseases/amyotrophic-lateral-sclerosis)
References
[Evans et al., Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist (2023)](https://pubmed.ncbi.nlm.nih.gov/36705554/)
[Pulvirenti et al., Clinical Associations of Biallelic and Monoallelic TNFRSF13B Variants (2016)](https://pubmed.ncbi.nlm.nih.gov/27123465/)
[Liu et al., TACI-Deficient Macrophages Protect Mice Against Metaflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/29871859/)
[Allman et al., TACI deficiency leads to alternatively activated macrophage phenotype (2015)](https://pubmed.ncbi.nlm.nih.gov/26170307/)
[Salzer et al., Relevance of biallelic versus monoallelic TNFRSF13B mutations (2009)](https://pubmed.ncbi.nlm.nih.gov/18981294/)
[Sabat et al., Neutrophilic granulocyte-derived B-cell activating factor (2023)](https://pubmed.ncbi.nlm.nih.gov/36481267/)
[Fan et al., Telitacicept, a novel humanized, recombinant TACI-Fc fusion protein (2022)](https://pubmed.ncbi.nlm.nih.gov/35107091/)
[Salzer et al., TACI deficiency - a complex system out of balance (2021)](https://pubmed.ncbi.nlm.nih.gov/34247095/)
[Eslami et al., Unique and redundant roles of mouse BCMA, TACI, BAFF, APRIL (2024)](https://pubmed.ncbi.nlm.nih.gov/38990948/)
[Abolhassani et al., Re-evaluation of the contribution of TNFRSF13B variants (2025)](https://pubmed.ncbi.nlm.nih.gov/40959164/)
[Went et al., Deciphering the genetics and mechanisms of predisposition to multiple myeloma (2024)](https://pubmed.ncbi.nlm.nih.gov/39103364/)
[Zan et al., Effect of Telitacicept on Circulating Gd-IgA1 (2024)](https://pubmed.ncbi.nlm.nih.gov/38765591/)
[Larson et al., Anti-TACI CAR T cells overcome BCMA antigen loss (2023)](https://pubmed.ncbi.nlm.nih.gov/37980341/)
[Castigli et al., TACI mutations in CVID (2005)](https://pubmed.ncbi.nlm.nih.gov/15809398/)
[Seshasayee et al., TACI function in B cells (2008)](https://pubmed.ncbi.nlm.nih.gov/18556557/)
[Gomez et al., TACI and BAFF in autoimmune disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22832214/)
[Mackay et al., The BAFF/APRIL system (2009)](https://pubmed.ncbi.nlm.nih.gov/19741154/)
[Cerutti et al., TACI controls class-switch recombination (2010)](https://pubmed.ncbi.nlm.nih.gov/20513757/)
[Sullivan et al., B cells in ALS (2015)](https://pubmed.ncbi.nlm.nih.gov/25663875/)
[Thon et al., TACI signaling in plasma cells (2017)](https://pubmed.ncbi.nlm.nih.gov/28742732/) Show full description