TRIM21

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External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
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Wikidata
View/Edit Human

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.

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 pathway. It recognizes Fc domain and binds to immunoglobulin G 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.

Clinical significance

RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus.

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.

Further reading

• Jones SK (1992). "Ultraviolet radiation (UVR) induces cell-surface Ro/SSA antigen expression by human keratinocytes in vitro: a possible mechanism for the UVR induction of cutaneous lupus lesions". Br. J. Dermatol. 126 (6): 546–553. doi:10.1111/j.1365-2133.1992.tb00098.x. PMID 1610705.
• Itoh K, Itoh Y, Frank MB (1991). "Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes". J. Clin. Invest. 87 (1): 177–186. doi:10.1172/JCI114968. PMC 295020. PMID 1985094.
• Chan EK, Hamel JC, Buyon JP, Tan EM (1991). "Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen". J. Clin. Invest. 87 (1): 68–76. doi:10.1172/JCI115003. PMC 294993. PMID 1985112.
• Miyagawa S, Okada N, Inagaki Y, et al. (1988). "SSA/Ro antigen expression in simian virus 40-transformed human keratinocytes". J. Invest. Dermatol. 90 (3): 342–345. doi:10.1111/1523-1747.ep12456308. PMID 2450143.
• Chan EK, Di Donato F, Hamel JC, et al. (1995). "52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal and adult heart". J. Exp. Med. 182 (4): 983–992. doi:10.1084/jem.182.4.983. PMC 2192297. PMID 7561701.
• Tsugu H, Horowitz R, Gibson N, Frank MB (1995). "The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)". Genomics. 24 (3): 541–548. doi:10.1006/geno.1994.1664. PMID 7713506.
• Frank MB, McCubbin VR, Heldermon C (1995). "Expression and DNA binding of the human 52 kDa Ro/SSA autoantigen". Biochem. J. 305 (2): 359–62. PMC 1136368. PMID 7832745.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Keech CL, Gordon TP, McCluskey J (1996). "Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species". Clin. Exp. Immunol. 104 (2): 255–263. doi:10.1046/j.1365-2249.1996.16726.x. PMC 2200432. PMID 8625517.
• Igarashi T, Itoh Y, Fukunaga Y, Yamamoto M (1996). "Stress-induced cell surface expression and antigenic alteration of the Ro/SSA autoantigen". Autoimmunity. 22 (1): 33–42. doi:10.3109/08916939508995297. PMID 8882420.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Bepler G, O'briant KC, Kim YC, et al. (1999). "A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region". Genomics. 55 (2): 164–175. doi:10.1006/geno.1998.5659. PMID 9933563.
• Tseng CE, Miranda E, Di Donato F, et al. (1999). "mRNA and protein expression of SSA/Ro and SSB/La in human fetal cardiac myocytes cultured using a novel application of the Langendorff procedure". Pediatr. Res. 45 (2): 260–269. doi:10.1203/00006450-199902000-00018. PMID 10022600.
• Fabini G, Rutjes SA, Zimmermann C, et al. (2000). "Analysis of the molecular composition of Ro ribonucleoprotein complexes. Identification of novel Y RNA-binding proteins". Eur. J. Biochem. 267 (9): 2778–2789. doi:10.1046/j.1432-1327.2000.01298.x. PMID 10785401.
• Kurien BT, Chambers TL, Thomas PY, et al. (2001). "Autoantibody to the leucine zipper region of 52 kDa Ro/SSA binds native 60 kDa Ro/SSA: identification of a tertiary epitope with components from 60 kDa Ro/SSA and 52 kDa Ro/SSA". Scand. J. Immunol. 53 (3): 268–276. doi:10.1046/j.1365-3083.2001.00870.x. PMID 11251884.
• Reymond A, Meroni G, Fantozzi A, et al. (2001). "The tripartite motif family identifies cell compartments". EMBO J. 20 (9): 2140–2151. doi:10.1093/emboj/20.9.2140. PMC 125245. PMID 11331580.
• Di Donato F, Chan EK, Askanase AD, et al. (2001). "Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function". Int. J. Biochem. Cell Biol. 33 (9): 924–934. doi:10.1016/S1357-2725(01)00055-3. PMID 11461834.
• Fukuda-Kamitani T, Kamitani T (2002). "Ubiquitination of Ro52 autoantigen". Biochem. Biophys. Res. Commun. 295 (4): 774–778. doi:10.1016/S0006-291X(02)00750-7. PMID 12127959.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.