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Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the TNFRSF13B
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. TNFRSF13B is a transmembrane protein of the
TNF receptor The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve gro ...
superfamily found predominantly on the surface of
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
, which are an important part of the immune system. TACI recognizes three ligands:
APRIL April is the fourth month of the year in the Gregorian and Julian calendars. It is the first of four months to have a length of 30 days, and the second of five months to have a length of less than 31 days. April is commonly associated with ...
, BAFF and
CAML Caml (originally an acronym for Categorical Abstract Machine Language) is a multi-paradigm, general-purpose programming language which is a dialect of the ML programming language family. Caml was developed in France at INRIA and ENS. Caml is ...
.


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: BAFF and APRIL. These proteins signal through TACI inducing activation of several transcription factors including
NFAT Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the developme ...
, 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. TACI controls T cell-independent B cell antibody responses,
isotype switching Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the ...
, and B cell
homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
.


Clinical significance

TACI mutations are associated with immunodeficiency in humans, as a significant proportion of CVID patients have TACI mutations. 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. TACI is currently being targeted for autoimmunity and B cell malignancies via
atacicept Atacicept is a recombinant fusion protein designed to inhibit B cells, thereby suppressing autoimmune disease. The designer protein combines the binding site for two cytokines that regulate maturation, function, and survival of B cells - B-lymph ...
, a recombinant fusion protein that binds the TACI ligands BAFF and
APRIL April is the fourth month of the year in the Gregorian and Julian calendars. It is the first of four months to have a length of 30 days, and the second of five months to have a length of less than 31 days. April is commonly associated with ...
.


Interactions

TNFRSF13B has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
B-cell activating factor 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) a ...
,
TRAF6 TRAF6 is a TRAF human protein. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF recep ...
,
TRAF5 TNF receptor-associated factor 5 is a protein that in humans is encoded by the ''TRAF5'' gene. Function The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and con ...
,
TNFSF13 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. Nomenclature In the cluster of differentiati ...
,
TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, an ...
and CAMLG.


References


Further reading

* * * * * * * * * * * * * * * * * * {{Cytokine receptor modulators Clusters of differentiation TNF receptor family