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Gene Review

Trim21  -  tripartite motif-containing 21

Mus musculus

Synonyms: 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, E3 ubiquitin-protein ligase TRIM21, Ro(SS-A), Ro52, ...
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Disease relevance of Trim21


High impact information on Trim21

  • The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability [1].
  • Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides [4].
  • The 2 mAb reacted with the Ro 52-kd antigen in cell extracts of human cell lines and mouse cell lines, and with purified human recombinant Ro 52-kd protein in ELISA and Western blot [5].
  • The role of polyclonal B-cell activation was examined by measuring total gamma-globulin as well as IgG reactive with other nuclear antigens including Ro60, Ro52 and La, which although not a major component of the autoantibody responses in these mice, did show small but significant increases following immunization with M. bovis [6].
  • The putative leucine-zipper and zinc-finger motifs present in human Ro52 were conserved in the mouse protein [7].

Biological context of Trim21

  • Ro52 may therefore rely upon an association with other molecules for any specific nuclear transport [8].
  • These results suggest that molecular mimicry between laminin and La, but not Ro52, may act as a target for specific maternal autoantibodies, and contribute to the pathogenesis of CHB at a critical stage during fetal cardiac development [9].
  • Other studies have shown that initiation of immunity to either Ro52 or 60 kDaRo (Ro60) can lead to reciprocal spreading of autoimmunity to Ro60 or Ro52, respectively, and induce anti-La autoantibodies in some strains of mice [10].

Anatomical context of Trim21

  • This relative localization was supported by a preponderance of the Ro52 antigen in the cytoplasmic rather than nuclear fraction of enucleated cell lines detected by immunoblotting [8].
  • Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway [1].
  • Thus, we suggested that the binding of IgG to the apoptotic keratinocytes might be mediated through the interactions with the surface exposed Ro52 [11].

Analytical, diagnostic and therapeutic context of Trim21

  • Immunofluorescence staining of human (HEp-2) and mouse (LTA-5) cell transfectants with affinity-purified anti-Ro52 antibodies revealed that Ro52 antigen was most abundant in the cytoplasm and present to a lesser extent in the nucleus [8].
  • METHODS: DNA and nucleosome antibodies were detected by ELISA, antibodies to SmB, U1A-RNP, Ro52, Ro60 and La by a new radioligand assay, using de novo synthesized radio-labeled antigens [12].


  1. The Sjogren's Syndrome-Associated Autoantigen Ro52 Is an E3 Ligase That Regulates Proliferation and Cell Death. Espinosa, A., Zhou, W., Ek, M., Hedlund, M., Brauner, S., Popovic, K., Horvath, L., Wallerskog, T., Oukka, M., Nyberg, F., Kuchroo, V.K., Wahren-Herlenius, M. J. Immunol. (2006) [Pubmed]
  2. Induction of neonatal lupus in pups of mice immunized with synthetic peptides derived from amino acid sequences of the serotoninergic 5-HT4 receptor. Eftekhari, P., Roegel, J.C., Lezoualc'h, F., Fischmeister, R., Imbs, J.L., Hoebeke, J. Eur. J. Immunol. (2001) [Pubmed]
  3. Characterization of T cell receptor repertoire and anti-Ro/SSA autoantibodies in relation to sialadenitis of NOD mice. Skarstein, K., Wahren, M., Zaura, E., Hattori, M., Jonsson, R. Autoimmunity (1995) [Pubmed]
  4. Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B). Farris, A.D., Brown, L., Reynolds, P., Harley, J.B., James, J.A., Scofield, R.H., McCluskey, J., Gordon, T.P. J. Immunol. (1999) [Pubmed]
  5. Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in primary Sjögren's syndrome. Elagib, K.E., Tengnér, P., Levi, M., Jonsson, R., Thompson, K.M., Natvig, J.B., Wahren-Herlenius, M. Arthritis Rheum. (1999) [Pubmed]
  6. Characterization and specificity of B-cell responses in lupus induced by Mycobacterium bovis in NOD/Lt mice. Horsfall, A.C., Howson, R., Silveira, P., Williams, D.G., Baxter, A.G. Immunology (1998) [Pubmed]
  7. Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species. Keech, C.L., Gordon, T.P., McCluskey, J. Clin. Exp. Immunol. (1996) [Pubmed]
  8. Cytoplasmic accumulation of the 52 kDa Ro/SS-A nuclear autoantigen in transfected cell lines. Keech, C.L., Gordon, T.P., McCluskey, J. J. Autoimmun. (1995) [Pubmed]
  9. Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin--a role in the pathogenesis of congenital heart block? Li, J.M., Horsfall, A.C., Maini, R.N. Clin. Exp. Immunol. (1995) [Pubmed]
  10. Spreading of the immune response from 52 kDaRo and 60 kDaRo to calreticulin in experimental autoimmunity. Kinoshita, G., Keech, C.L., Sontheimer, R.D., Purcell, A., McCluskey, J., Gordon, T.P. Lupus (1998) [Pubmed]
  11. Autoantigen Ro52 directly interacts with human IgG heavy chain in vivo in mammalian cells. Yang, Y.S., Yang, M.C., Wang, B., Weissler, J.C. Mol. Immunol. (2000) [Pubmed]
  12. Concomitant early appearance of anti-ribonucleoprotein and anti-nucleosome antibodies in lupus prone mice. Laderach, D., Koutouzov, S., Bach, J.F., Yamamoto, A.M. J. Autoimmun. (2003) [Pubmed]
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