TRIM21

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.^[5][6] 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.^[7]

TRIM21
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2IWG
Identifiers
Aliases	TRIM21, RNF81, RO52, Ro/SSA, SSA, SSA1, tripartite motif containing 21, Tripartite motif-containing protein 21
External IDs	OMIM: 109092; MGI: 106657; HomoloGene: 2365; GeneCards: TRIM21; OMA:TRIM21 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.4 Start 4,384,897 bp[1] End 4,393,702 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 E3 Start 102,207,128 bp[2] End 102,214,693 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte blood mucosa of transverse colon spleen rectum epithelium of colon apex of heart Descending thoracic aorta mucosa of ileum Top expressed in Ileal epithelium Paneth cell mesenteric lymph nodes lumbar spinal ganglion thymus blood granulocyte carotid body spleen Epithelium of choroid plexus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding zinc ion binding metal ion binding protein binding RNA binding identical protein binding ubiquitin-protein transferase activity transferase activity Cellular component cytoplasm cytosol SCF ubiquitin ligase complex P-body intracellular anatomical structure autophagosome cytoplasmic vesicle nucleus nucleoplasm ribonucleoprotein complex Biological process negative regulation of protein deubiquitination response to interferon-gamma positive regulation of autophagy interferon-gamma-mediated signaling pathway protein trimerization positive regulation of viral entry into host cell positive regulation of DNA-binding transcription factor activity protein monoubiquitination regulation of type I interferon production positive regulation of cell cycle protein destabilization protein ubiquitination cell cycle negative regulation of NF-kappaB transcription factor activity protein autoubiquitination innate immune response protein polyubiquitination negative regulation of viral transcription Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6737 20821 Ensembl ENSG00000132109 ENSMUSG00000030966 UniProt P19474 Q62191 RefSeq (mRNA) NM_003141 NM_001082552 NM_009277 RefSeq (protein) NP_003132 n/a Location (UCSC) Chr 11: 4.38 – 4.39 Mb Chr 7: 102.21 – 102.21 Mb PubMed search [3] [4]
Wikidata
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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.^[6]

Function

TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It recognizes Fc domain^[8] and binds to immunoglobulin G, immunoglobulin A^[9] and 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.^[7]

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.^[6]

Clinical significance

RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus.^[6] 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.^[10]

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.^[11]