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Gene Review

TRIM21  -  tripartite motif containing 21

Homo sapiens

Synonyms: 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, E3 ubiquitin-protein ligase TRIM21, RING finger protein 81, RNF81, ...
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Disease relevance of TRIM21


Psychiatry related information on TRIM21

  • The linguistic performance of 120 aphasic patients of the four standard syndromes assessed by the Aachen Aphasia Test (AAT) is analyzed by a nonmetric (ordinal) multidimensional scaling procedure (Smallest Space Analysis, SSA1) [6].

High impact information on TRIM21

  • 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 [4].
  • In addition to the cDNA clone we previously reported for the full-length 52-kD SS-A/Ro protein, an interesting MOLT-4 cDNA clone, p52-2, was found to have an internal deletion of 231 nucleotides including the domain encoding the leucine zipper motif [4].
  • In an attempt to analyze the regulated gene expression in lymphocytes by an HIV-suppressive immunomodulator, we have identified and cloned a novel gene encoding a 56-kDa protein, named SS-56, which is structurally related to the 52-kDa Ro/SSA antigen [7].
  • Serum SS-A/Ro autoantibodies are commonly found in patients with Sjogren's syndrome, systemic lupus erythematosus, neonatal lupus, and subacute cutaneous lupus [8].
  • Two cDNA clones encoding the 52-kD form of a protein present in human Ro/SSA ribonucleoprotein complexes were cloned from a lambda gt11 human thymocyte cDNA library [9].

Biological context of TRIM21

  • The identity of cDNA was established by (a) the specificity of the antibody affinity purified from the recombinant protein, (b) the reactivity of the purified recombinant protein with prototype SS-A/Ro sera in immunoblot and ELISA, and (c) two-dimensional gel comigration of MOLT-4 cell 52-kD protein and the recombinant protein [8].
  • We previously isolated and determined the nucleotide sequence of a cDNA clone that encodes the 52-kD form of the human Ro/SSA protein [5].
  • The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms [5].
  • Maternal antibody responses to the 52-kd SSA/RO p200 peptide and the development of fetal conduction defects [10].
  • OBJECTIVE: To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52-kd SSA/Ro (Ro 52) [10].

Anatomical context of TRIM21

  • In this study, we describe the role of Ro52 protein in T cell activation [11].
  • These results indicate that expression of SSA/Ro antigen in human keratinocytes is modulated by SV40 infection and that this antigen is expressed to a greater degree in cells that are less differentiated, transformed, or proliferating [12].
  • La/SS-B and/or 52 kDa Ro antigen(s) were found to be present in the cytoplasm of the B lymphoblastoid cells at a higher base level in EBV-infected cell lines than in the EBV-negative cell lines [13].
  • Patients with several different connective tissue diseases including Sjögren's syndrome and systemic lupus erythematosus produce autoantibodies reacting with a 52kD protein component of the Ro/SS-A antigen [14].
  • The results showed that keratinocytes receiving UVB irradiation expressed Ro/SSA antigen on cell membranes in a dose-dependent fashion [15].

Associations of TRIM21 with chemical compounds

  • Effective separation of the 52 kDa SSA/Ro polypeptide from the 48 kDa SSB/La polypeptide by altering conditions of polyacrylamide gel electrophoresis [16].
  • 17beta-estradiol treatment also induced Ro/SSA antigen expression dose-dependently [15].
  • The reaction to SSA but not to MAM suggested the presence of sialic acid linked alpha2,6 to galactose in both cellular and serum TNX [17].

Physical interactions of TRIM21


Other interactions of TRIM21

  • These data indicate that autoantibody responses to the 60-kDa Ro Ag can preferentially target discontinuous epitopes and that the ability to recognize continuous epitopes is accompanied by the appearance of 52-kDa Ro autoantibodies [19].
  • Antibodies were affinity purified from a peptide within the leucine zipper region of 52 kDa Ro [18].
  • Our data reveal a novel function of Ro52 in CD28-mediated pathway, which eventually contributes to cytokine production and expression of the T cell biological programs [11].
  • The region contains the complete SSA/Ro52 and RRM1 genes, exons 7-12 of the GOK gene, and the psirad pseudo-gene [20].
  • Contrary to the data published by other authors, our results indicate that calreticulin is not a Ro/SS-A autoantigen [21].

Analytical, diagnostic and therapeutic context of TRIM21

  • In fact, peptides from 60 kDa Ro have a molecular interaction with the 52 kDa Ro peptide as well as full-length 52 kDa Ro when assessed by surface plasmon resonance [18].
  • To measure serum antibody levels, ELISA using purified recombinant TRIM21 protein was developed [22].
  • The presence of s-TRIM21-Abs was confirmed by Western blotting using bacterially expressed TRIM21 gene product and was evaluated for clinicopathological significance in patients with esophageal SCC. s-TRIM21-Abs were detected in 18 (20%) of 91 patients with esophageal SCC but not in 42 healthy donors [22].
  • Immunoprecipitation of in vitro-translated 35S-labeled 52 beta form was performed to evaluate the antigenicity of this novel form of 52-kD SS-A/Ro [4].
  • The locations of SSA/Ro, U1RNP, and DNA antigens were studied by indirect immunofluorescence using monospecific antibodies [12].


  1. TRIM21 is a trimeric protein that binds IgG Fc via the B30.2 domain. Rhodes, D.A., Trowsdale, J. Mol. Immunol. (2007) [Pubmed]
  2. Functional replacement of the RING, B-box 2, and coiled-coil domains of tripartite motif 5alpha (TRIM5alpha) by heterologous TRIM domains. Li, X., Li, Y., Stremlau, M., Yuan, W., Song, B., Perron, M., Sodroski, J. J. Virol. (2006) [Pubmed]
  3. Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. Diaz-Griffero, F., Li, X., Javanbakht, H., Song, B., Welikala, S., Stremlau, M., Sodroski, J. Virology (2006) [Pubmed]
  4. 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. Chan, E.K., Di Donato, F., Hamel, J.C., Tseng, C.E., Buyon, J.P. J. Exp. Med. (1995) [Pubmed]
  5. The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms. Frank, M.B., Itoh, K., Fujisaku, A., Pontarotti, P., Mattei, M.G., Neas, B.R. Am. J. Hum. Genet. (1993) [Pubmed]
  6. Facet theory applied to the construction and validation of the Aachen Aphasia Test. Willmes, K., Poeck, K., Weniger, D., Huber, W. Brain and language. (1983) [Pubmed]
  7. SS-56, a novel cellular target of autoantibody responses in Sjögren syndrome and systemic lupus erythematosus. Billaut-Mulot, O., Cocude, C., Kolesnitchenko, V., Truong, M.J., Chan, E.K., Hachula, E., de la Tribonnière, X., Capron, A., Bahr, G.M. J. Clin. Invest. (2001) [Pubmed]
  8. Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen. Chan, E.K., Hamel, J.C., Buyon, J.P., Tan, E.M. J. Clin. Invest. (1991) [Pubmed]
  9. Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes. Itoh, K., Itoh, Y., Frank, M.B. J. Clin. Invest. (1991) [Pubmed]
  10. Maternal antibody responses to the 52-kd SSA/RO p200 peptide and the development of fetal conduction defects. Clancy, R.M., Buyon, J.P., Ikeda, K., Nozawa, K., Argyle, D.A., Friedman, D.M., Chan, E.K. Arthritis Rheum. (2005) [Pubmed]
  11. SS-A/Ro52, an autoantigen involved in CD28-mediated IL-2 production. Ishii, T., Ohnuma, K., Murakami, A., Takasawa, N., Yamochi, T., Iwata, S., Uchiyama, M., Dang, N.H., Tanaka, H., Morimoto, C. J. Immunol. (2003) [Pubmed]
  12. SSA/Ro antigen expression in simian virus 40-transformed human keratinocytes. Miyagawa, S., Okada, N., Inagaki, Y., Kitano, Y., Ueki, H., Sakamoto, K., Steinberg, M.L. J. Invest. Dermatol. (1988) [Pubmed]
  13. Effect of ultraviolet irradiation on selected host cell proteins including Ro/SS-A and Epstein-Barr virus in cultured lymphoblastoid cell lines. Newkirk, M.M., Tsoukas, C. J. Autoimmun. (1992) [Pubmed]
  14. Identification of antigenic regions of the human 52kD Ro/SS-A protein recognized by patient sera. Blange, I., Ringertz, N.R., Pettersson, I. J. Autoimmun. (1994) [Pubmed]
  15. Induction of Ro/SSA antigen expression on keratinocyte cell membrane by heat shock and phorbol 12-myristate 13-acetate as well as estradiol and ultraviolet B. Zhang, J., Xu, Z., Jin, J., Zhu, T., Ma, S. J. Dermatol. Sci. (2000) [Pubmed]
  16. Effective separation of the 52 kDa SSA/Ro polypeptide from the 48 kDa SSB/La polypeptide by altering conditions of polyacrylamide gel electrophoresis. Buyon, J.P., Slade, S.G., Chan, E.K., Tan, E.M., Winchester, R. J. Immunol. Methods (1990) [Pubmed]
  17. Distinct glycosylation in interstitial and serum tenascin-x. Kinoshita, T., Ariga, H., Matsumoto, K. Biol. Pharm. Bull. (2007) [Pubmed]
  18. 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. Kurien, B.T., Chambers, T.L., Thomas, P.Y., Frank, M.B., Scofield, R.H. Scand. J. Immunol. (2001) [Pubmed]
  19. 60-kDa Ro protein autoepitopes identified using recombinant polypeptides. Saitta, M.R., Arnett, F.C., Keene, J.D. J. Immunol. (1994) [Pubmed]
  20. Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer. Zhao, B., Bepler, G. Oncogene (2001) [Pubmed]
  21. Characterization of the autoantigen calreticulin. Rokeach, L.A., Haselby, J.A., Meilof, J.F., Smeenk, R.J., Unnasch, T.R., Greene, B.M., Hoch, S.O. J. Immunol. (1991) [Pubmed]
  22. Presence of serum tripartite motif-containing 21 antibodies in patients with esophageal squamous cell carcinoma. Kuboshima, M., Shimada, H., Liu, T.L., Nomura, F., Takiguchi, M., Hiwasa, T., Ochiai, T. Cancer Sci. (2006) [Pubmed]
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