Tripartite motif-containing protein 21, also known as E3 ubiquitin-protein ligase TRIM21, 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 ''TRIM21''
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 ...
.
Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.
Structure
TRIM21 is a member of the
tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a
RING finger domain, a B-box type 1 and a B-box type 2
zinc finger, and a
coiled coil region.
Function
TRIM21 is an intracellular antibody effector in the
intracellular antibody-mediated proteolysis Intracellular antibody-mediated degradation (IAMD) is a neutralization mechanism of intracellular antibody-mediated immunity whereby an effector protein, TRIM21, directs antibody bound virions to the proteasome where they are degraded. As yet, it h ...
pathway. It recognizes
Fc domain
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune ...
and binds to
immunoglobulin G
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...
,
immunoglobulin A and
immunoglobulin M
Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
on antibody marked non-enveloped virions which have infected the cell. Either by
autoubiquitination or by ubiquitination of a cofactor, it is then responsible for directing the virions to the
proteasome. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.
TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.
Clinical significance
RoSSA interacts with autoantigens in patients with
Sjögren's syndrome and
systemic lupus erythematosus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...
.
In addition, the inability for lupus-prone macrophages to degrade immune complexes in the lysosome results in the leakage of autoantibodies into the cytosol that can bind to TRIM21 and enhance NF-κB signaling.
TRIM21 can be used to knockout specific proteins with their corresponding antibodies, a method known as Trim-Away. In this assay, TRIM21 and antibodies are delivered into cells through
electroporation, and the targeted protein is degraded within a few minutes.
References
Further reading
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{{PDB Gallery, geneid=6737