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Gene Review

TMBIM4  -  transmembrane BAX inhibitor motif...

Homo sapiens

Synonyms: CGI-119, GAAP, Golgi anti-apoptotic protein, LFG4, Protein S1R, ...
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Disease relevance of TMBIM4


High impact information on TMBIM4

  • Once folded, however, the native Z protein shows substantial stability towards urea and incubation at 37 degrees C. The folding defect in Z antitrypsin leads to accumulation of an intermediate and it is the intermediate rather than the native protein which has a high tendency to aggregate [4].
  • A carbohydrate chain could be prevented from attaching to the Z type either because of a conformational change or because of the replacement of a carbohydrate-binding asparagine residue in the Z protein [5].
  • It is proposed that the Z protein lacks a carbohydrate chain with two terminal sialic acid residues [5].
  • This interaction requires the coiled-coil dimerization domain of the Z protein and the carboxy-terminal portion of p53 [6].
  • The Z protein, which has homology to the basic leucine zipper protein c-Fos, transactivates the promoters of several replicative cycle proteins [7].

Biological context of TMBIM4


Anatomical context of TMBIM4


Associations of TMBIM4 with chemical compounds


Other interactions of TMBIM4

  • Mutational analysis of the Z protein revealed that, in addition to all three functional domains of Z (dimerization domain, DNA binding domain, and activation domain), the carboxyl terminal 17 amino acids which stabilize the Z protein were necessary for induction of MMP9 expression [17].
  • We found that SUMO-1 modification of Z has no apparent effect upon the stability and localization of the Z protein [18].
  • The presence of desmin and Z-protein strongly suggests the myogenic character of this tumor [19].
  • Liver fatty acid binding protein (L-FABP), a cytoplasmic 14 kDa protein previously termed Z protein, is conventionally considered to be an intracellular carrier of fatty acids in rat hepatocytes [20].
  • The biologic t1/2 of both M and Z protein in the circulation were similar, averaging 71 hr for M protein and 80 hr for Z protein [21].

Analytical, diagnostic and therapeutic context of TMBIM4

  • This lineage was found to have alpha 1-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS) [22].
  • MDA-MB-361, MDA-MB-435, BT20 and MCF7 cells all expressed S1R protein by Western blot [14].
  • Accumulation of Z protein has also been demonstrated by immunocytochemistry [23].
  • S1R expression was neither a prognostic nor a predictive factor for efficacy of adjuvant chemotherapy but the study only included 58 cancer patients and therefore the statistical power is limited [14].
  • The S1R-specific ligand, SKF 10047 demonstrated the least growth inhibitory activity and showed no interaction with chemotherapy [14].


  1. A low molecular weight binding protein for organic anions (Z protein) from human hepatic cytosol: purification and quantitation. Kamisaka, n.u.l.l., Maezawa, H., Inagaki, T., Okano, K. Hepatology (1981) [Pubmed]
  2. Immunoperoxidase demonstration of a new muscle protein (Z-protein) in myogenic tumors as a diagnostic aid. Mukai, M., Iri, H., Torikata, C., Kageyama, K., Morikawa, Y., Shimizu, K. Am. J. Pathol. (1984) [Pubmed]
  3. RAZ, an Epstein-Barr virus transdominant repressor that modulates the viral reactivation mechanism. Furnari, F.B., Zacny, V., Quinlivan, E.B., Kenney, S., Pagano, J.S. J. Virol. (1994) [Pubmed]
  4. The Z type variation of human alpha 1-antitrypsin causes a protein folding defect. Yu, M.H., Lee, K.N., Kim, J. Nat. Struct. Biol. (1995) [Pubmed]
  5. The effect of neuraminidase on genetic variants of alpha anitrypsin. Cox, D.W. Am. J. Hum. Genet. (1975) [Pubmed]
  6. Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency. Zhang, Q., Gutsch, D., Kenney, S. Mol. Cell. Biol. (1994) [Pubmed]
  7. The bZIP transactivator of Epstein-Barr virus, BZLF1, functionally and physically interacts with the p65 subunit of NF-kappa B. Gutsch, D.E., Holley-Guthrie, E.A., Zhang, Q., Stein, B., Blanar, M.A., Baldwin, A.S., Kenney, S.C. Mol. Cell. Biol. (1994) [Pubmed]
  8. Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene. Nukiwa, T., Satoh, K., Brantly, M.L., Ogushi, F., Fells, G.A., Courtney, M., Crystal, R.G. J. Biol. Chem. (1986) [Pubmed]
  9. Replicon system for Lassa virus. Hass, M., Gölnitz, U., Müller, S., Becker-Ziaja, B., Günther, S. J. Virol. (2004) [Pubmed]
  10. The Tacaribe arenavirus small zinc finger protein is required for both mRNA synthesis and genome replication. Garcin, D., Rochat, S., Kolakofsky, D. J. Virol. (1993) [Pubmed]
  11. The amino acid substitutions of human alpha 1-antitrypsin M3, X and Z. Jeppsson, J.O., Laurell, C.B. FEBS Lett. (1988) [Pubmed]
  12. Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency. Rudnick, D.A., Shikapwashya, O., Blomenkamp, K., Teckman, J.H. Hepatology (2006) [Pubmed]
  13. Xenopus oocytes can synthesise but do not secrete the Z variant of human alpha 1-antitrypsin. Foreman, R.C., Judah, J.D., Colman, A. FEBS Lett. (1984) [Pubmed]
  14. Expression of sigma 1 receptor in human breast cancer. Wang, B., Rouzier, R., Albarracin, C.T., Sahin, A., Wagner, P., Yang, Y., Smith, T.L., Meric-Bernstam, F., Marcelo Aldaz, C., Marcelo, A.C., Hortobagyi, G.N., Pusztai, L. Breast Cancer Res. Treat. (2004) [Pubmed]
  15. Binding of bile acids, oleic acid, and organic anions by rat and human hepatic Z protein. Takikawa, H., Kaplowitz, N. Arch. Biochem. Biophys. (1986) [Pubmed]
  16. The in vitro effect of lithocholic acid on the polymerization properties of PiZ alpha-1-antitrypsin. Gerbod, M.C., Janciauskiene, S., Jeppsson, J.O., Eriksson, S. Arch. Biochem. Biophys. (1998) [Pubmed]
  17. Matrix metalloproteinase 9 is induced by the Epstein-Barr virus BZLF1 transactivator. Yoshizaki, T., Sato, H., Murono, S., Pagano, J.S., Furukawa, M. Clin. Exp. Metastasis (1999) [Pubmed]
  18. Effects of SUMO-1 upon Epstein-Barr virus BZLF1 function and BMRF1 expression. Adamson, A.L. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  19. Histogenesis of alveolar soft part sarcoma. An immunohistochemical and biochemical study. Mukai, M., Torikata, C., Iri, H., Mikata, A., Hanaoka, H., Kato, K., Kageyama, K. Am. J. Surg. Pathol. (1986) [Pubmed]
  20. Modulation of mitogenesis by liver fatty acid binding protein. Sorof, S. Cancer Metastasis Rev. (1994) [Pubmed]
  21. Biologic half-life and organ distribution of radiolabeled human PiM and PiZ alpha-1-antitrypsin in the dog. Moser, K.M., Kidikoro, Y., Marsh, J., Sgroi, V. J. Lab. Clin. Med. (1978) [Pubmed]
  22. Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. Dycaico, M.J., Grant, S.G., Felts, K., Nichols, W.S., Geller, S.A., Hager, J.H., Pollard, A.J., Kohler, S.W., Short, H.P., Jirik, F.R. Science (1988) [Pubmed]
  23. Evaluation of a transgenic mouse model for alpha-1-antitrypsin (AAT) related liver disease. Ali, R., Perfumo, S., della Rocca, C., Amicone, L., Pozzi, L., McCullagh, P., Millward-Sadler, H., Edwards, Y., Povey, S., Tripodi, M. Ann. Hum. Genet. (1994) [Pubmed]
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