Transmembrane activator and CAML interactor

Last updated
TNFRSF13B
Protein TNFRSF13B PDB 1xu1.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez

23495

57916

Ensembl

ENSG00000240505

ENSMUSG00000010142

UniProt

O14836

Q9ET35

RefSeq (mRNA)

NM_012452

NM_021349

RefSeq (protein)

NP_036584

NP_067324

Location (UCSC) Chr 17: 16.93 – 16.97 Mb Chr 11: 61.02 – 61.04 Mb
PubMed search [3] [4]
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.

Contents

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]

Related Research Articles

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<span class="mw-page-title-main">B-cell activating factor</span> Mammalian protein found in Homo sapiens

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B and CD257 among other names, is a protein that in humans is encoded by the TNFSF13B gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule.

<span class="mw-page-title-main">CD137</span> Member of the tumor necrosis factor (TNF) receptor family

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<span class="mw-page-title-main">Tumor necrosis factor receptor 1</span> Membrane receptor protein found in humans

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<span class="mw-page-title-main">TRAF1</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

<span class="mw-page-title-main">Lymphotoxin alpha</span> Protein found in humans

Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene. Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.

<span class="mw-page-title-main">TRAF3</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.

<span class="mw-page-title-main">APRIL (protein)</span> Protein-coding gene in the species Homo sapiens

A proliferation-inducing ligand (APRIL), also known as tumor necrosis factor ligand superfamily member 13 (TNFSF13), is a protein of the TNF superfamily recognized by the cell surface receptor TACI. It is encoded by the TNFSF13 gene.

<span class="mw-page-title-main">LIGHT (protein)</span> Secreted protein of the TNF superfamily

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<span class="mw-page-title-main">BAFF receptor</span> Mammalian protein found in Homo sapiens

BAFF receptor, also known as tumor necrosis factor receptor superfamily member 13C (TNFRSF13C) and BLyS receptor 3 (BR3), is a membrane protein of the TNF receptor superfamily which recognizes BAFF, an essential factor for B cell maturation and survival. In humans it is encoded by the TNFRSF13C gene.

<span class="mw-page-title-main">B-cell maturation antigen</span> Protein-coding gene in the species Homo sapiens

B-cell maturation antigen, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.

<span class="mw-page-title-main">Calcium modulating ligand</span> Protein-coding gene in humans

Calcium modulating ligand, also known as calcium-modulating cyclophilin ligand, is a signalling protein recognized by the TNF receptor TACI.

<span class="mw-page-title-main">TNFRSF18</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced TNFR-related protein (GITR) or CD357. GITR is encoded and tnfrsf18 gene at chromosome 4 in mice. GITR is type I transmembrane protein and is described in 4 different isoforms. GITR human orthologue, also called activation-inducible TNFR family receptor (AITR), is encoded by the TNFRSF18 gene at chromosome 1.

<span class="mw-page-title-main">TNFSF12-TNFSF13</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor (ligand) superfamily, member 12-member 13, also known as TNFSF12-TNFSF13, is a human gene.

<span class="mw-page-title-main">Tumor necrosis factor receptor 2</span> Membrane receptor protein found in humans

Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).

<span class="mw-page-title-main">TACI-CRD2 protein domain</span>

In molecular biology, TACI-CRD2 represents the second cysteine-rich protein domain found in the TACI family of proteins. Members of this family are predominantly found in tumour necrosis factor receptor superfamily, member 13b (TACI), and are required for binding to the ligands APRIL and BAFF. TACI-CRD2 stands for Transmembrane Activator and CAML Interactor- Cysteine Rich Domain 2.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000240505 – Ensembl, May 2017
  2. 1 2 3 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.
  5. 1 2 "Entrez Gene: TNFRSF13B tumor necrosis factor receptor superfamily, member 13B".
  6. 1 2 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.
  10. 1 2 3 4 5 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.
  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.

Further reading

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