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Gene Review

TROVE2  -  TROVE domain family, member 2

Homo sapiens

Synonyms: 60 kDa Ro protein, 60 kDa SS-A/Ro ribonucleoprotein, 60 kDa ribonucleoprotein Ro, RO60, RORNP, ...
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Disease relevance of TROVE2


Psychiatry related information on TROVE2

  • In this communication, we review the induction of autoimmune diseases via Id manipulation, the Ids of some ANA-associated Abs (DNA, SS-A, SS- B, Sm Abs), the pathogenic role of Abs carrying Ids, and the clinical implications of the Id network in autoimmunity [6].

High impact information on TROVE2

  • To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human SLE back in time, prior to clinical disease onset, and identified the initial autoantigenic epitope for some lupus patients positive for antibodies to 60 kDa Ro [7].
  • Many lupus and Sjögren's syndrome patients, as well as most neonatal lupus infants with congenital heart block or dermatitis, have antibodies to the ribonucleoprotein Ro/SSA, which is one of a group of RNA-protein autoantigens commonly found in human lupus sera [8].
  • These data indicate that the Id-Rol epitope on anti-Ro/SSA is associated with the antigen binding site of these same antibodies [8].
  • The rheumatic disease autoantigen, Ro/SSA, was immunogenic to a rabbit host [9].
  • By yeast 2-hybrid screening, we identified a novel 75-kDa protein (pp75) that interacts with the carboxyl 70% of 60-kDa SS-A/Ro [2].

Chemical compound and disease context of TROVE2

  • Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus [10].
  • The main risk factors for adverse pregnancy course and outcome are active disease, nephritis with proteinuria, hypertension, and maternal serum antibodies to SS-A/Ro, SS-B/La, cardiolipin, beta2-glycoprotein I, and lupus anticoagulant [11].
  • They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course [12].
  • Decreased levels of autoantibodies against DNA, histones, cardiolipin, RNP, Sm, Ro (SS-A), and La (SS-B) were detected in the sera of patients with uveitis receiving cyclosporine A or cyclosporine A plus bromocriptine following 3 months of treatment [13].

Biological context of TROVE2

  • The sequence of the cDNA shows that the 60-kD SS-A/Ro protein possesses both RNA binding protein consensus sequences and a single zinc-finger motif [1].
  • The availability of the 60-kD SS-A/Ro cDNA will enable detailed analysis of the molecular structure and function of the SS-A/Ro RNP particle and its role in autoimmune pathology [1].
  • Mapping of the human 60,000 M(r) Ro/SSA locus: the genes for three Ro/SSA autoantigens are located on separate chromosomes [14].
  • The predominant antibody response in the NLE group was to the newly recognized 52-kD SSA/Ro peptide component [15].
  • RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls [16].

Anatomical context of TROVE2


Associations of TROVE2 with chemical compounds


Physical interactions of TROVE2

  • These purified antibodies binding the 197-207 peptide from 52 kDa Ro (anti-52LZ) bound native 60 kDa Ro as well as denatured 52 kDa Ro [25].
  • The SS-A/SS-B autoantigenic complex: localization and assembly [26].
  • Other RNA polymerase III products such as the cellular Ro RNAs continue to be transcribed and assembled into ribonucleoprotein complexes containing the Ro (SS-A) antigens [27].

Other interactions of TROVE2

  • Based on Western blot and ELISA assays, sera from 14 of 84 mothers of children with NLE recognized pp75, including 1 mother in whom anti-SS-A/Ro antibodies were not detected [2].
  • 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 [28].
  • Overall agreement of positive or negative tests between the ALBIA and IB, LIA and ELISA was 75% for chromatin, 50% for SS-A, 27.5% for Sm, 25% for Rib-P, 22.5% for RNP, 20% for Scl-70, 15% for Jo-1 and 7.5% for SS-B [29].
  • The mRNA levels of calreticulin increased as a function of time after UV irradiation but the mRNA levels of 52 kDa and 60 kDa Ro mRNAs were unaltered [20].
  • Isolation and characterization of a cDNA clone encoding the 60-kD component of the human SS-A/Ro ribonucleoprotein autoantigen [1].

Analytical, diagnostic and therapeutic context of TROVE2


  1. Isolation and characterization of a cDNA clone encoding the 60-kD component of the human SS-A/Ro ribonucleoprotein autoantigen. Ben-Chetrit, E., Gandy, B.J., Tan, E.M., Sullivan, K.F. J. Clin. Invest. (1989) [Pubmed]
  2. Defining a novel 75-kDa phosphoprotein associated with SS-A/Ro and identification of distinct human autoantibodies. Wang, D., Buyon, J.P., Zhu, W., Chan, E.K. J. Clin. Invest. (1999) [Pubmed]
  3. Disparate locations of the 52- and 60-kDa Ro/SS-A antigens in cultured human keratinocytes. Yell, J.A., Wang, L., Yin, H., McCauliffe, D.P. J. Invest. Dermatol. (1996) [Pubmed]
  4. The detection of anti-Ro/SS-A and anti-La/SS-B antibodies. A comparison of counterimmunoelectrophoresis with immunoblot, ELISA, and RNA-precipitation assays. Meilof, J.F., Bantjes, I., De Jong, J., Van Dam, A.P., Smeenk, R.J. J. Immunol. Methods (1990) [Pubmed]
  5. Clinical significances of antibodies to Ro/SS-A autoantigens and its subtypes in primary Sjögren's syndrome. Cho, C.S., Park, S.H., Min, J.K., Lee, S.H., Kim, H.Y. Korean J. Intern. Med. (1997) [Pubmed]
  6. The idiotypic network in antinuclear-antibody-associated diseases. Sherer, Y., Shoenfeld, Y. Int. Arch. Allergy Immunol. (2000) [Pubmed]
  7. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. McClain, M.T., Heinlen, L.D., Dennis, G.J., Roebuck, J., Harley, J.B., James, J.A. Nat. Med. (2005) [Pubmed]
  8. A shared idiotype among human anti-Ro/SSA autoantibodies. Gaither, K.K., Harley, J.B. J. Exp. Med. (1989) [Pubmed]
  9. The Ro/SSA autoantigen as an immunogen. Some anti-Ro/SSA antibody binds IgG. Mamula, M.J., Fox, O.F., Yamagata, H., Harley, J.B. J. Exp. Med. (1986) [Pubmed]
  10. Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus. Furukawa, F., Lyons, M.B., Lee, L.A., Coulter, S.N., Norris, D.A. J. Immunol. (1988) [Pubmed]
  11. Systemic lupus erythematosus and pregnancy. Molad, Y. Curr. Opin. Obstet. Gynecol. (2006) [Pubmed]
  12. A study of 20 SLE patients with intravenous immunoglobulin--clinical and serologic response. Levy, Y., Sherer, Y., Ahmed, A., Langevitz, P., George, J., Fabbrizzi, F., Terryberry, J., Meissner, M., Lorber, M., Peter, J.B., Shoenfeld, Y. Lupus (1999) [Pubmed]
  13. Down-regulation of autoantibody levels of cyclosporine and bromocriptine treatment in patients with uveitis. Blank, M., Palestine, A., Nussenblatt, R., Shoenfeld, Y. Clin. Immunol. Immunopathol. (1990) [Pubmed]
  14. Mapping of the human 60,000 M(r) Ro/SSA locus: the genes for three Ro/SSA autoantigens are located on separate chromosomes. Frank, M.B., Mattei, M.G. Immunogenetics (1994) [Pubmed]
  15. Acquired congenital heart block. Pattern of maternal antibody response to biochemically defined antigens of the SSA/Ro-SSB/La system in neonatal lupus. Buyon, J.P., Ben-Chetrit, E., Karp, S., Roubey, R.A., Pompeo, L., Reeves, W.H., Tan, E.M., Winchester, R. J. Clin. Invest. (1989) [Pubmed]
  16. Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B among Japanese subjects. Miyagawa, S., Shinohara, K., Nakajima, M., Kidoguchi, K., Fujita, T., Fukumoto, T., Yoshioka, A., Dohi, K., Shirai, T. Arthritis Rheum. (1998) [Pubmed]
  17. Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological and pathological findings as well as the salivary gland dysfunction of Sjogren's syndrome. Scofield, R.H., Asfa, S., Obeso, D., Jonsson, R., Kurien, B.T. J. Immunol. (2005) [Pubmed]
  18. New coupled-particle light-scattering assay for detection of Ro/SSA (52 and 60 kilodaltons) and La/SSB autoantibodies in connective tissue diseases. Bizzaro, N., Bonelli, F., Tonutti, E., Tozzoli, R., Villalta, D. Clin. Diagn. Lab. Immunol. (2001) [Pubmed]
  19. Can B cell epitopes of 60 kDa Ro distinguish systemic lupus erythematosus from Sjögren's syndrome? Scofield, A.N., Kurien, B.T., Gordon, T.P., Scofield, R.H. Lupus (2001) [Pubmed]
  20. UVB light and 17-beta-estradiol have different effects on the mRNA expression of Ro/SSA and La/SSB autoantigens in HaCaT cells. Szegedi, A., Irinyi, B., Bessenyei, B., Márka, M., Hunyadi, J., Semsei, I. Arch. Dermatol. Res. (2001) [Pubmed]
  21. Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype. Mendlovic, S., Brocke, S., Shoenfeld, Y., Ben-Bassat, M., Meshorer, A., Bakimer, R., Mozes, E. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  22. Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. Comparison of enzyme-linked immunosorbent assay and immunoblot for measurement of anti-SS-A/Ro and anti-SS-B/La antibodies. Buyon, J.P., Winchester, R.J., Slade, S.G., Arnett, F., Copel, J., Friedman, D., Lockshin, M.D. Arthritis Rheum. (1993) [Pubmed]
  23. Immunoglobulin class and subclass profile of the Ro/SS-A autoantibody response. Lieu, T.S., Reimer, C.B., Sontheimer, R.D. J. Invest. Dermatol. (1988) [Pubmed]
  24. Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus. Furukawa, F., Kashihara-Sawami, M., Lyons, M.B., Norris, D.A. J. Invest. Dermatol. (1990) [Pubmed]
  25. 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]
  26. The SS-A/SS-B autoantigenic complex: localization and assembly. Peek, R., van Venrooij, W.J., Simons, F., Pruijn, G. Clinical and experimental rheumatology. (1994) [Pubmed]
  27. The use of adenovirus-infected HeLa cells for the detection of low titer autoantibodies. Slobbe, R., Van Esch, B., Kveder, T., Van Venrooij, W.J. J. Immunol. Methods (1991) [Pubmed]
  28. 60-kDa Ro protein autoepitopes identified using recombinant polypeptides. Saitta, M.R., Arnett, F.C., Keene, J.D. J. Immunol. (1994) [Pubmed]
  29. Analysis of human sera that are polyreactive in an addressable laser bead immunoassay. Fritzler, M.J., Behmanesh, F., Fritzler, M.L. Clin. Immunol. (2006) [Pubmed]
  30. Human 60-kDa SS-A/Ro ribonucleoprotein autoantigen gene (SSA2) localized to 1q31 by fluorescence in situ hybridization. Chan, E.K., Tan, E.M., Ward, D.C., Matera, A.G. Genomics (1994) [Pubmed]
  31. Anti-Ro/SSA and La/SSB antibodies. Franceschini, F., Cavazzana, I. Autoimmunity (2005) [Pubmed]
  32. Routine immunofluorescence detection of Ro/SS-A autoantibody using HEp-2 cells transfected with human 60 kDa Ro/SS-A. Pollock, W., Toh, B.H. J. Clin. Pathol. (1999) [Pubmed]
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