TRIM21
Encyclopedia
Tripartite motif-containing protein 21 also known as E3 ubiquitin-protein ligase TRIM21 is a protein
that in humans is encoded by the TRIM21 gene
. 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.
(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.
as well as immunoglobulin M
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.
and systemic lupus erythematosus
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the TRIM21 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. 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 motifTripartite motif family
-Function:Many TRIM proteins are induced by interferons, which are important component of resistance to pathogens and several TRIM proteins are known to be required for the restriction of infection by lentiviruses...
(TRIM) family. The TRIM motif includes three zinc-binding domains, a RING finger domain
RING finger domain
In molecular biology, a RING finger domain is a protein structural domain of zinc finger type which contains a Cys3HisCys4 amino acid motif which binds two zinc cations. This protein domain contains from 40 to 60 amino acids...
, a B-box type 1 and a B-box type 2 zinc finger
Zinc finger
Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
, and a coiled coil
Coiled coil
A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...
region.
Function
TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It binds to immunoglobulin GImmunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
as well as immunoglobulin M
Immunoglobulin M
Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...
on antibody marked non-enveloped virions which have infected the cell. Either by autoubiquitination
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
or by ubiquitination of a cofactor, it is then responsible for directing the virions to the proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
. 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 syndromeSjögren's syndrome
Sjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
and systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
.