TACI Protein (Transmembrane Activator and Calcium Modulator)

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TACI Protein (Transmembrane Activator and Calcium Modulator)

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TACI Protein (Transmembrane Activator and Calcium Modulator)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TACI Protein (Transmembrane Activator and Calcium Modulator)</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[TNFRSF13B](/genes/tnfrsf13b)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[O14836](https://www.uniprot.org/uniprot/O14836)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>32.5 kDa</td>
</tr>
<tr>
<td class="label">Length</td>
<td>295 amino acids</td>
</tr>
<tr>
<td class="label">Cellular Location</td>
<td>Cell surface (type I transmembrane)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>TNF Receptor Superfamily</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>TACI, CD256, TNFR2</td>
</tr>
<tr>
<td class="label">Ligands</td>
<td>BAFF, APRIL</td>
</tr>
<tr>
<td class="label">Pathway</td>
<td>Outcome</td>
</tr>
<tr>
<td class="label">NF-κB (canonical)</td>
<td>Gene transcription</td>
</tr>
<tr>
<td class="label">NF-κB (non-canonical)</td>
<td>B cell maturation</td>
</tr>
<tr>
<td class="label">MAPK/ERK</td>
<td>Cell survival</td>
</tr>
<tr>
<td class="label">PI3K/AKT</td>
<td>B cell survival</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Belimumab</td>
<td>BAFF inhibitor</td>
</tr>
<tr>
<td class="label">Telitacicept</td>
<t

...

TACI Protein (Transmembrane Activator and Calcium Modulator)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TACI Protein (Transmembrane Activator and Calcium Modulator)</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[TNFRSF13B](/genes/tnfrsf13b)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[O14836](https://www.uniprot.org/uniprot/O14836)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>32.5 kDa</td>
</tr>
<tr>
<td class="label">Length</td>
<td>295 amino acids</td>
</tr>
<tr>
<td class="label">Cellular Location</td>
<td>Cell surface (type I transmembrane)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>TNF Receptor Superfamily</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>TACI, CD256, TNFR2</td>
</tr>
<tr>
<td class="label">Ligands</td>
<td>BAFF, APRIL</td>
</tr>
<tr>
<td class="label">Pathway</td>
<td>Outcome</td>
</tr>
<tr>
<td class="label">NF-κB (canonical)</td>
<td>Gene transcription</td>
</tr>
<tr>
<td class="label">NF-κB (non-canonical)</td>
<td>B cell maturation</td>
</tr>
<tr>
<td class="label">MAPK/ERK</td>
<td>Cell survival</td>
</tr>
<tr>
<td class="label">PI3K/AKT</td>
<td>B cell survival</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Belimumab</td>
<td>BAFF inhibitor</td>
</tr>
<tr>
<td class="label">Telitacicept</td>
<td>TACI-Fc fusion</td>
</tr>
<tr>
<td class="label">Povetacicept</td>
<td>Dual APRIL/BAFF antagonist</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">BAFF</td>
<td>Ligand</td>
</tr>
<tr>
<td class="label">APRIL</td>
<td>Ligand</td>
</tr>
<tr>
<td class="label">TRAF2</td>
<td>Signaling</td>
</tr>
<tr>
<td class="label">TRAF6</td>
<td>Signaling</td>
</tr>
<tr>
<td class="label">BCMA</td>
<td>Receptor</td>
</tr>
<tr>
<td class="label">TWEAK</td>
<td>Ligand</td>
</tr>
<tr>
<td class="label">Model</td>
<td>Phenotype</td>
</tr>
<tr>
<td class="label">TACI knockout</td>
<td>B cell defects</td>
</tr>
<tr>
<td class="label">TACI transgenic</td>
<td>Autoimmunity</td>
</tr>
<tr>
<td class="label">TNFRsf13b-/- mice</td>
<td>CVID-like</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

:: 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 signal
Cysteine-rich domain (CRD1, 15-46 aa): First ligand-binding domain
CRD2 (47-79 aa): Second ligand-binding domain
Transmembrane domain (80-102 aa): Single pass membrane anchor
Cytoplasmic 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 cells
Receptors: TACI, BCMA, BR3
Function: B cell survival, maturation
Affinity: TACI binds BAFF with moderate affinity (Kd ~ 10⁻⁸ M)

APRIL (TNFSF13)

Expression: Produced by immune cells, tumor cells
Receptors: TACI, BCMA
Function: Class switch recombination, plasma cell survival
Affinity: TACI binds APRIL with higher affinity

Normal Physiological Function

B Cell Biology

TACI regulates multiple aspects of B cell function:

B cell maturation: Promotes transitional B cell survival
Class switch recombination (CSR): Essential for IgA, IgG, IgE production
Plasma cell survival: Supports long-lived plasma cells
Immune homeostasis: Prevents autoimmunity via B cell regulation

Signaling 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 patients
Mutation types: Heterozygous and biallelic variants
Phenotype: Antibody deficiency, infections
Incomplete penetrance: Not all carriers develop CVID
Treatment: Immunoglobulin replacement

Multiple Myeloma

TACI is a therapeutic target in multiple myeloma:

Expression: MM cells express TACI
Autocrine signaling: BAFF/APRIL promote survival
Telitacicept: TACI-Fc fusion protein in trials
CAR T cells: Anti-TACI CAR T cells in development

Amyotrophic Lateral Sclerosis

Connections between TACI and ALS:

Neuroinflammation: B cell involvement in ALS
BAFF levels: Elevated in ALS patient serum
Neuroimmune interactions: Cross-talk between CNS and immune system
Therapeutic potential: BAFF/APRIL blockade

Autoimmune 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 cells
BCMA-loss escape: Alternative to BCMA-targeting
Clinical trials: Showing promise in MM

Interaction Network

TACI interacts with:

Clinical Significance

Biomarker: TACI expression predicts treatment response
Genetic testing: TNFRSF13B variants in CVID diagnosis
Therapeutic target: Multiple drug candidates in development

Animal Models

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/)

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Related Entities

TACI

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-taci
kg_node_id	TACI
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ff0b4538f469
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-taci'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

310

Outgoing

311

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

TACI Protein (Transmembrane Activator and Calcium Modulator)

TACI Protein (Transmembrane Activator and Calcium Modulator)

TACI Protein (Transmembrane Activator and Calcium Modulator)

Overview

Molecular Structure

Ligand Interactions

BAFF (TNFSF13B)

APRIL (TNFSF13)

Normal Physiological Function

B Cell Biology

Signaling Pathways

Role in Disease

Common Variable Immunodeficiency (CVID)

Multiple Myeloma

Amyotrophic Lateral Sclerosis

Autoimmune Disorders

Therapeutic Targeting

TACI-Fc Fusion Proteins

CAR T Cell Therapy

Interaction Network

Clinical Significance

Animal Models

See Also

References

💬 Discussion