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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''TNFRSF13B''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
TNFRSF13B is a transmembrane protein of the
TNF receptor superfamily found predominantly on the surface of
B cells
B cells, also known as B lymphocytes, are a type 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 or inserted into the plasm ...
, 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. Its length is 30 days.
April is commonly associated with the season of spring in the Northern Hemisphere, and autumn in the Southern Hemisphere, where it is the ...
,
BAFF and
CAML
Caml (originally an acronym for Categorical Abstract Machine Language) is a multi-paradigm, general-purpose, high-level, functional programming language which is a dialect of the ML programming language family. Caml was developed in France ...
.
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).
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 English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...
.
Clinical significance
TACI mutations are associated with immunodeficiency in humans, as a significant proportion of
common variable immunodeficiency (CVID) patients have TACI mutations. People with this condition produce abnormally low amounts of
antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
, which are needed for protection against infections.
In humans, the gene encoding this protein is located within the
Smith–Magenis syndrome
Smith–Magenis syndrome (SMS), also known as 17p-microdeletion syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome 17. It has features including intellectual disability, facial abnormalities, ...
region on chromosome 17.
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.
Interactions
TNFRSF13B has been shown to
interact with
B-cell activating factor,
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 rece ...
,
,
,
[ ]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, a ...
References
Further reading
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{{Cytokine receptor modulators
Clusters of differentiation
TNF receptor family