TRIM21

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TRIM21
Protein TRIM21 PDB 2iwg.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTRIM21, RNF81, RO52, Ro/SSA, SSA, SSA1, tripartite motif containing 21, Tripartite motif-containing protein 21
External IDsOMIM: 109092 MGI: 106657 HomoloGene: 2365 GeneCards: TRIM21
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003141

NM_001082552
NM_009277

RefSeq (protein)

NP_003132

n/a

Location (UCSC)Chr 11: 4.38 – 4.39 MbChr 7: 102.21 – 102.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Structure[edit]

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[edit]

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[edit]

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]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000132109 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030966 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Frank MB, Itoh K, Fujisaku A, Pontarotti P, Mattei MG, Neas BR (January 1993). "The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms". American Journal of Human Genetics. 52 (1): 183–91. PMC 1682114. PMID 8094596.
  6. ^ a b c d "Entrez Gene: TRIM21 tripartite motif-containing 21".
  7. ^ a b Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC (November 2010). "Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)". Proceedings of the National Academy of Sciences of the United States of America. 107 (46): 19985–90. Bibcode:2010PNAS..10719985M. doi:10.1073/pnas.1014074107. PMC 2993423. PMID 21045130.
  8. ^ James LC, Keeble AH, Khan Z, Rhodes DA, Trowsdale J (April 2007). "Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function". Proceedings of the National Academy of Sciences of the United States of America. 104 (15): 6200–5. Bibcode:2007PNAS..104.6200J. doi:10.1073/pnas.0609174104. PMC 1851072. PMID 17400754.
  9. ^ Bidgood, Susanna; Tam, Jerry; McEwan, William; Mallery, Donna; James, Leo (2014). "Translocalized IgA mediates neutralization and stimulates innate immunity inside infected cells". Proceedings of the National Academy of Sciences of the United States of America. 111 (37): 13463–8. Bibcode:2014PNAS..11113463B. doi:10.1073/pnas.1410980111. PMC 4169910. PMID 25169018.
  10. ^ Monteith AJ, Kang S, Scott E, Hillman K, Rajfur Z, Jacobson K, Costello MJ, Vilen BJ (April 2016). "Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus". Proceedings of the National Academy of Sciences of the United States of America. 113 (15): E2142–51. Bibcode:2016PNAS..113E2142M. doi:10.1073/pnas.1513943113. PMC 4839468. PMID 27035940.
  11. ^ Clift D, McEwan WA, Labzin LI, Konieczny V, Mogessie B, James LC, Schuh M (December 2017). "A Method for the Acute and Rapid Degradation of Endogenous Proteins". Cell. 171 (7): 1692–1706.e18. doi:10.1016/j.cell.2017.10.033. PMC 5733393. PMID 29153837.

Further reading[edit]