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Gene Review

BTG3  -  BTG family, member 3

Homo sapiens

Synonyms: ANA, Abundant in neuroepithelium area protein, BTG family member 3, Protein BTG3, Protein Tob5, ...
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Disease relevance of BTG3

  • Tob55 belongs to an evolutionarily conserved protein family, the members of which are present in almost all eukaryotes and in Gram-negative bacteria and chloroplasts [1].
  • The present data confirm that pANCA, although less prevalent in our series than in other reports, do associate with AIH-1 also in the Mediterranean area and show that it can identify a small subgroup (13%) of ANA/SMA positive chronic hepatitis C, in which autoimmune reactions might play a more relevant role than viral infection [2].
  • In this study, inhibition of FA synthesis at the physiologically regulated step of carboxylation of acetyl-CoA to malonyl-CoA by 5-(tetradecyloxy)-2-furoic acid (TOFA) was not cytotoxic to breast cancer cells in clonogenic assays [3].
  • These findings suggest that antibodies to Ro and La may be a marker for systemic disease in ANA-negative patients with 1) cutaneous lupus and 2) a distinct subpopulation of patients with a lupus-like syndrome without skin disease [4].
  • Thus the striking differences in the prevalence of nephritis among these patients with high titer ANA cannot be explained by differences in complement fixation by these antibodies [5].

Psychiatry related information on BTG3

  • Thus, the polymorphism in the ALDH2 gene does not explain the acetaldehyde accumulation in ANA rats and it does not seem to be associated with differences in the alcohol drinking behavior in these rat lines [6].
  • ANA positivity in FDRs occurred randomly, irrespective of family relationship [7].
  • ANA decision-making process deserves discussion [8].
  • Is the ANA guilty of paternalism in its guidelines on withdrawing or withholding food and fluid [9]?
  • The ANA Standards of Psychiatric and Mental Health Nursing Practice (1982) provides a broad framework for the nurse case manager [10].

High impact information on BTG3

  • The key component of this pathway is Tob55 (also known as Sam50) in mitochondria and Omp85 in bacteria, both beta-barrel membrane proteins themselves [1].
  • We studied the structure-function relationships of the core component of the TOB complex, Tob55 [11].
  • The N-terminal domain of Tob55 has a receptor-like function in the biogenesis of mitochondrial {beta}-barrel proteins [11].
  • A cDNA clone (CL ANA 11) with 571 bases 5' of the C beta coding sequence has an open reading frame starting at a methionine codon that encodes 141 amino acids in frame with the C beta sequence [12].
  • C75 triggered apoptosis during S phase, whereas TOFA did not [13].

Chemical compound and disease context of BTG3

  • Thirty-three of 130 ANA-positive SLE patients, but none of 16 discoid lupus patients, possessed these anticytoplasmic antibodies [4].
  • METHODS: We describe the clinical presentation, course, and outcome of 4 patients and review the medical literature registered in the Medline PubMed database from 1966 to 2004 by using the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis, arthritis, rash, ANA, and ANCA [14].
  • Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus [15].
  • In SLE, anti-MDA-modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0.702, P = 0.0001), anti-nuclear antigen autoantibodies (ANA, r = 0.4, P = 0.029), IgG anti-cardiolipin (r = 0.558, P = 0.03) and the steroid drug regimen (r = 0.52, P = 0.004) [16].
  • (4) Known non-organ specific antibodies behaved as expected on beef conducting fibres: striational fluorescence of myasthenia gravis sera reacted with the same patterns on Purkinje myofibrils; AMA and ANA produced IFL in expected locations; ribosomal antibodies reacted strongly, while LKM and reticulin antibodies showed no reactivity [17].

Biological context of BTG3

  • We report here the cloning of the mouse BTG3 gene and show that its human counterpart maps on chromosome 21 [18].
  • Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle [18].
  • Moreover, application of TOFA 2 h before C75 blocked the C75 induced apoptosis, whereas etomoxir did not [13].
  • ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P < .001) [19].
  • In search of novel neural substrates for this phenotype, we compared gene expression in the cerebral cortex of the AA rat with two groups of control animals, the ANA (alcohol non-accepting) line and heterogeneous Wistar animals, by differential display RT-PCR [20].

Anatomical context of BTG3

  • Replacement of wild-type Tob55 by these deletion variants resulted in reduced growth of cells, and mitochondria isolated from such cells were impaired in their capacity to import beta-barrel precursors [11].
  • In conclusion, ANA is a fourth member of the Tob/BTG1 family that might play roles in neurogenesis in the central nervous system [21].
  • 1. ANA was expressed in a variety of tissues and cell lines, its expression being high in the ovary, testis, prostate, thymus, and lung [21].
  • Antibodies to nuclei (ANA), smooth muscle (SMA), and liver/kidney microsomes type 1 (anti-LKM1) may occur in chronic hepatitis C [22].
  • If cell lysis results, antibodies can then be made to the cell (lymphocytotoxic antibodies) or cell products (ANA, etc.). The antibodies-to-lymphocyte membranes may interfere with lymphocyte function in a number of ways, including immunosuppression, and may also cause reactivation of this cycle [23].

Associations of BTG3 with chemical compounds

  • At presentation: 56% had symptoms of prolonged acute hepatitis; LKM-1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM-1 positive were cirrhotic (P = .080) [19].
  • FAS inhibitors induced a rapid increase in intracellular malonyl-CoA to several fold above control levels, whereas TOFA reduced intracellular malonyl-CoA by 60% [3].
  • A pyrimidine oligoarabinonucleotide (ANA) was shown to form triple-helical complexes only with duplex DNA and hybrid DNA (Pu):RNA (Py) with an affinity that was slightly lower relative to the corresponding pyrimidine oligodeoxynucleotide (DNA) third strand [24].
  • NAPA therapy was well tolerated by the 6 patients and ANA titers became abnormal in only one, in marked contrast to reported experience with procainamide [25].
  • Cerulenin and TOFA each inhibited the endogenous synthesis of fatty acids in a dose-dependent manner and each induced increases in both precursor and mature forms of SREBP-1 [26].

Analytical, diagnostic and therapeutic context of BTG3

  • Molecular cloning and analysis of cDNAs revealed that the human and mouse ANA encoded a protein of 252 amino acids [21].
  • Finally, in situ hybridization experiments revealed that expression of Caf1 overlaps at least in part with that of ANA [27].
  • Compared with AIH, HCV-associated ANA and SMA exhibited ANA-H and SMA-AA at a lower prevalence (38% vs. 71%, P = .04 and 8% vs. 87%, P < .000001, respectively) and had a lower median titer (1:80 vs. 1:320, P < .001 and 1:40 vs. 1:320, P < .000001, respectively) [22].
  • Of six (5 LKM-1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression [19].
  • The ANA pattern was defined by IFL on HEp-2 cells and the SMA-AA identified by the presence of at least two of the following elements: 1) SMA(T) or SMA(G) pattern by IFL on kidney sections; 2) XR1 precipitating system by counterimmunoelectrophoresis; or 3) typical pattern by IFL on liver sections from phalloidin-intoxicated rats [22].


  1. Biogenesis of beta-barrel membrane proteins of mitochondria. Paschen, S.A., Neupert, W., Rapaport, D. Trends Biochem. Sci. (2005) [Pubmed]
  2. Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis. Zauli, D., Ghetti, S., Grassi, A., Descovich, C., Cassani, F., Ballardini, G., Muratori, L., Bianchi, F.B. Hepatology (1997) [Pubmed]
  3. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Pizer, E.S., Thupari, J., Han, W.F., Pinn, M.L., Chrest, F.J., Frehywot, G.L., Townsend, C.A., Kuhajda, F.P. Cancer Res. (2000) [Pubmed]
  4. Antibodies to cytoplasmic antigens in lupus erythematosus. Serologic marker for systemic disease. Provost, T.T., Razzaque, A., Maddison, P.J., Reichlin, M. Arthritis Rheum. (1977) [Pubmed]
  5. Comparison of the complement-fixing activity of antinuclear antibodies in lupus nephritis, mixed connective tissue disease, and scleroderma. Parker, M.D., Turner, R.A. Arthritis Rheum. (1976) [Pubmed]
  6. Mitochondrial aldehyde dehydrogenase (ALDH2) polymorphism in AA and ANA rats: lack of genotype and phenotype line differences. Koivisto, T., Carr, L.G., Li, T.K., Eriksson, C.J. Pharmacol. Biochem. Behav. (1993) [Pubmed]
  7. Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach. Laustrup, H., Heegaard, N.H., Voss, A., Green, A., Lillevang, S.T., Junker, P. Lupus (2004) [Pubmed]
  8. ANA decision-making process deserves discussion. Cole, E. The American nurse. (1983) [Pubmed]
  9. Is the ANA guilty of paternalism in its guidelines on withdrawing or withholding food and fluid? Light, K., Connelly, R. Nursing forum. (1989) [Pubmed]
  10. What does a nurse need to know and do to maintain an effective level of case management? Connolly, P.M. Journal of psychosocial nursing and mental health services. (1992) [Pubmed]
  11. The N-terminal domain of Tob55 has a receptor-like function in the biogenesis of mitochondrial {beta}-barrel proteins. Habib, S.J., Waizenegger, T., Niewienda, A., Paschen, S.A., Neupert, W., Rapaport, D. J. Cell Biol. (2007) [Pubmed]
  12. Identification of genes for the constant region of rabbit T-cell receptor beta chains. Angiolillo, A.L., Lamoyi, E., Bernstein, K.E., Mage, R.G. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  13. Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Zhou, W., Simpson, P.J., McFadden, J.M., Townsend, C.A., Medghalchi, S.M., Vadlamudi, A., Pinn, M.L., Ronnett, G.V., Kuhajda, F.P. Cancer Res. (2003) [Pubmed]
  14. Propylthiouracil-induced autoimmune syndromes: two distinct clinical presentations with different course and management. Aloush, V., Litinsky, I., Caspi, D., Elkayam, O. Semin. Arthritis Rheum. (2006) [Pubmed]
  15. Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus. Federmann, M., Morell, B., Graetz, G., Wyss, M., Elsner, P., von Thiessen, R., Wüthrich, B., Grob, D. Ann. Rheum. Dis. (1994) [Pubmed]
  16. Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides. Amara, A., Constans, J., Chaugier, C., Sebban, A., Dubourg, L., Peuchant, E., Pellegrin, J.L., Leng, B., Conri, C., Geffard, M. Clin. Exp. Immunol. (1995) [Pubmed]
  17. Autoantibodies to cardiac conducting tissue and their characterization by immunofluorescence. Fairfax, A., Doniach, D. Clin. Exp. Immunol. (1976) [Pubmed]
  18. Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle. Guéhenneux, F., Duret, L., Callanan, M.B., Bouhas, R., Hayette, S., Berthet, C., Samarut, C., Rimokh, R., Birot, A.M., Wang, Q., Magaud, J.P., Rouault, J.P. Leukemia (1997) [Pubmed]
  19. Autoimmune hepatitis in childhood: a 20-year experience. Gregorio, G.V., Portmann, B., Reid, F., Donaldson, P.T., Doherty, D.G., McCartney, M., Mowat, A.P., Vergani, D., Mieli-Vergani, G. Hepatology (1997) [Pubmed]
  20. Differential expression of diacylglycerol kinase iota and L18A mRNAs in the brains of alcohol-preferring AA and alcohol-avoiding ANA rats. Sommer, W., Arlinde, C., Caberlotto, L., Thorsell, A., Hyytia, P., Heilig, M. Mol. Psychiatry (2001) [Pubmed]
  21. ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system. Yoshida, Y., Matsuda, S., Ikematsu, N., Kawamura-Tsuzuku, J., Inazawa, J., Umemori, H., Yamamoto, T. Oncogene (1998) [Pubmed]
  22. Serum autoantibodies in chronic hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile. Cassani, F., Cataleta, M., Valentini, P., Muratori, P., Giostra, F., Francesconi, R., Muratori, L., Lenzi, M., Bianchi, G., Zauli, D., Bianchi, F.B. Hepatology (1997) [Pubmed]
  23. Pathophysiology of rheumatic diseases. Schur, P.H. Arthritis Rheum. (1977) [Pubmed]
  24. Triple helices containing arabinonucleotides in the third (Hoogsteen) strand: effects of inverted stereochemistry at the 2'-position of the sugar moiety. Noronha, A., Damha, M.J. Nucleic Acids Res. (1998) [Pubmed]
  25. Long-term antiarrhythmic therapy with N-acetylprocainamide. Lertora, J.J., Atkinson, A.J., Kushner, W., Nevin, M.J., Lee, W.K., Jones, C., Schmid, F.R. Clin. Pharmacol. Ther. (1979) [Pubmed]
  26. Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia. Li, J.N., Mahmoud, M.A., Han, W.F., Ripple, M., Pizer, E.S. Exp. Cell Res. (2000) [Pubmed]
  27. Association of ANA, a member of the antiproliferative Tob family proteins, with a Caf1 component of the CCR4 transcriptional regulatory complex. Yoshida, Y., Hosoda, E., Nakamura, T., Yamamoto, T. Jpn. J. Cancer Res. (2001) [Pubmed]
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