:: infobox .infobox-protein
| TACI Protein | |
|---|---|
| Gene | TNFRSF13B |
| UniProt | O14836 |
| Molecular Weight | 32.5 kDa |
| Length | 295 amino acids |
| Cellular Location | Cell surface (type I transmembrane) |
| Protein Family | TNF Receptor Superfamily |
| Aliases | TACI, CD256, TNFR2 |
| Ligands | BAFF, APRIL |
===
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).
TACI is a 295-amino acid type I transmembrane protein with:
The extracellular CRDs are characteristic of TNF receptor family members and bind BAFF/APRIL as trimeric ligands.
TACI regulates multiple aspects of B cell function:
TACI activates several signaling cascades:
| Pathway | Outcome |
|---|---|
| NF-κB (canonical) | Gene transcription |
| NF-κB (non-canonical) | B cell maturation |
| MAPK/ERK | Cell survival |
| PI3K/AKT | B cell survival |
TACI is one of the most commonly mutated genes in CVID:
TACI is a therapeutic target in multiple myeloma:
Connections between TACI and ALS:
TACI dysfunction linked to autoimmunity:
| Drug | Mechanism | Status |
|---|---|---|
| Belimumab | BAFF inhibitor | Approved (SLE) |
| Telitacicept | TACI-Fc fusion | Phase III |
| Povetacicept | Dual APRIL/BAFF antagonist | Phase I/II |
TACI interacts with:
| Partner | Interaction | Function |
|---|---|---|
| BAFF | Ligand | B cell activation |
| APRIL | Ligand | CSR, plasma cell survival |
| TRAF2 | Signaling | NF-κB activation |
| TRAF6 | Signaling | NF-κB activation |
| BCMA | Receptor | Synergistic signaling |
| TWEAK | Ligand | Cytokine signaling |
| Model | Phenotype | Key Findings |
|---|---|---|
| TACI knockout | B cell defects | B cell maturation blocked |
| TACI transgenic | Autoimmunity | B cell hyperactivity |
| TNFRsf13b-/- mice | CVID-like | Antibody deficiency |