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Gene Review

MT1G  -  metallothionein 1G

Homo sapiens

Synonyms: MT-1G, MT-1K, MT-IG, MT1, MT1K, ...
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Disease relevance of MT1G

  • Our studies show that the MT-IF and MT-IG genes are differentially regulated in two human hepatoma cell lines, HepG2 and Hep3B2, and a human lymphoblastoid cell line, WI-L2 in response to the heavy metals cadmium, zinc and copper, and glucocorticoids [1].
  • MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule [2].
  • Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment.RESULTS: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples [2].
  • The expression of three human metallothionein genes, MT-IIA, MT-IF, and MT-IG was studied in the human hepatoblastoma (HepG2), the hepatocarcinoma (Hep3B2), the embryonic kidney (Hek 293), and the lymphoblastoid-derived (Wi-L2) cell lines [3].
  • Expression of a dominant-positive G(alphai2) protein, with which the MT1 receptor has been shown to couple, is able to mimic the effect of melatonin on ERalpha but not RARalpha transcriptional activation in breast cancer cells [4].

High impact information on MT1G

  • This phenotype was mimicked by the cytoplasmic truncation mutant MT1 Delta C with more robust pro-MMP-2 activation and cell surface expression than wild-type MT1-MMP in transfected cells [5].
  • Internalization experiments revealed that MT1-MMP is internalized rapidly in clathrin-coated vesicles whereas MT1 Delta C remains on cell surface [5].
  • The level of expression of a transfected metallothionein (MT)-IGcat fusion gene in response to cadmium differed from that of the endogenous MT-IG gene [6].
  • OBJECTIVE: To detect the message for membrane type 1 (MT1) matrix metalloproteinase (MMP) in articular cartilage and chondrosarcoma cells, to study its expression in osteoarthritis (OA), and to determine whether interleukin-1beta (IL-1beta) influences its expression [7].
  • In both systems, mutations of the TATA box and conserved core of metal responsive element (MRE)a were detrimental to hMT-IG promoter activity suggesting that both elements make significant contributions to hMT-IG transcription [8].

Chemical compound and disease context of MT1G


Biological context of MT1G


Anatomical context of MT1G


Associations of MT1G with chemical compounds

  • The MT-IF or MT-IG and the MT-IIA genes were regulated in a cell-type specific manner in response to heavy metals and dexamethasone, respectively [3].
  • In the presence of Cd2+, MT-IG promoter activity and endogenous mRNA level were, respectively, 4.7- and 3-fold greater than those of MT-IF [14].
  • Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors [11].
  • Cd(2+) and Zn(2+) induced metallothionein IIa to five times higher levels than metallothionein Ig [15].
  • The rate of reaction of NO with these amino acid/proteins was found to be of the order: cysteine > BSA >> MT1, in clear disparity with the size of the reactants [16].

Other interactions of MT1G

  • Based on these findings, we conclude that induction of the hMT1G promoter by VEGF and heavy metals occurs through the utilization of different transcription factors [10].
  • We can find no previous observation in the literature of metallothionein-1g at both the protein and RNA level in a non-tumour cell, and of metallothionein-0 in a non-fetal cell or tissue [17].
  • The human metallothionein (MT)-IG gene (hMT-IG) is tandemly linked in a head-to-head fashion with the hMT-IF gene [18].
  • For all 3 HPT isolates, the expression of MT protein and mRNA for the MT-2A, MT-1E, MT-1F and MT-1G isoforms was similar among the isolates and demonstrated no correlation to lethality [19].

Analytical, diagnostic and therapeutic context of MT1G


  1. Structure and expression of the human metallothionein genes. Gedamu, L., Varshney, U., Jahroudi, N., Foster, R., Shworak, N.W. Experientia Suppl. (1987) [Pubmed]
  2. MT1G hypermethylation is associated with higher tumor stage in prostate cancer. Henrique, R., Jerónimo, C., Hoque, M.O., Nomoto, S., Carvalho, A.L., Costa, V.L., Oliveira, J., Teixeira, M.R., Lopes, C., Sidransky, D. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  3. Cell-type specific and differential regulation of the human metallothionein genes. Correlation with DNA methylation and chromatin structure. Jahroudi, N., Foster, R., Price-Haughey, J., Beitel, G., Gedamu, L. J. Biol. Chem. (1990) [Pubmed]
  4. Differential regulation of estrogen receptor alpha, glucocorticoid receptor and retinoic acid receptor alpha transcriptional activity by melatonin is mediated via different G proteins. Kiefer, T.L., Lai, L., Yuan, L., Dong, C., Burow, M.E., Hill, S.M. J. Pineal Res. (2005) [Pubmed]
  5. Regulation of membrane-type matrix metalloproteinase 1 activity by dynamin-mediated endocytosis. Jiang, A., Lehti, K., Wang, X., Weiss, S.J., Keski-Oja, J., Pei, D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  6. Calcium phosphate-mediated transfection alters metallothionein gene expression in response to Cd2+ and Zn2+. Foster, R., Olsson, P.E., Gedamu, L. Mol. Cell. Biol. (1989) [Pubmed]
  7. Expression of membrane type 1 matrix metalloproteinase in human articular cartilage. Büttner, F.H., Chubinskaya, S., Margerie, D., Huch, K., Flechtenmacher, J., Cole, A.A., Kuettner, K.E., Bartnik, E. Arthritis Rheum. (1997) [Pubmed]
  8. Functional analyses of the human metallothionein-IG gene. In vitro and in vivo studies. Samson, S.L., Paramchuk, W.J., Shworak, N.W., Gedamu, L. J. Biol. Chem. (1995) [Pubmed]
  9. Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma. Huang, Y., de la Chapelle, A., Pellegata, N.S. Int. J. Cancer (2003) [Pubmed]
  10. Induction of human metallothionein 1G promoter by VEGF and heavy metals: differential involvement of E2F and metal transcription factors. Joshi, B., Ordonez-Ercan, D., Dasgupta, P., Chellappan, S. Oncogene (2005) [Pubmed]
  11. Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors. Mailliet, F., Audinot, V., Malpaux, B., Bonnaud, A., Delagrange, P., Migaud, M., Barrett, P., Viaud-Massuard, M.C., Lesieur, D., Lefoulon, F., Renard, P., Boutin, J.A. Biochem. Pharmacol. (2004) [Pubmed]
  12. Maternal melatonin effects on clock gene expression in a nonhuman primate fetus. Torres-Farfan, C., Rocco, V., Monsó, C., Valenzuela, F.J., Campino, C., Germain, A., Torrealba, F., Valenzuela, G.J., Seron-Ferre, M. Endocrinology (2006) [Pubmed]
  13. Testing the eukaryotic promoters for efficient expression of exogenous genes in chondrocytes and synoviocytes. Su, S., Gedamu, L., Dehnade, F., Zafarullah, M. FEBS Lett. (1996) [Pubmed]
  14. Distinct TATA motifs regulate differential expression of human metallothionein I genes MT-IF and MT-IG. Shworak, N.W., O'Connor, T., Wong, N.C., Gedamu, L. J. Biol. Chem. (1993) [Pubmed]
  15. Activation of metallothioneins and alpha-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses. Hawse, J.R., Cumming, J.R., Oppermann, B., Sheets, N.L., Reddy, V.N., Kantorow, M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  16. Steric effect and effect of metal coordination on the reactivity of nitric oxide with cysteine-containing proteins under anaerobic conditions. Aravindakumar, C.T., Ceulemans, J., De Ley, M. Biophys. Chem. (2000) [Pubmed]
  17. Induction by zinc of specific metallothionein isoforms in human monocytes. Pauwels, M., van Weyenbergh, J., Soumillion, A., Proost, P., De Ley, M. Eur. J. Biochem. (1994) [Pubmed]
  18. Structure and expression of the human metallothionein-IG gene. Differential promoter activity of two linked metallothionein-I genes in response to heavy metals. Foster, R., Jahroudi, N., Varshney, U., Gedamu, L. J. Biol. Chem. (1988) [Pubmed]
  19. Exposure of human proximal tubule cells to cytotoxic levels of CdCl2 induces the additional expression of metallothionein 1A mRNA. Bylander, J.E., Li, S.L., Sens, M.A., Sens, D.A. Toxicol. Lett. (1995) [Pubmed]
  20. MT1-MMP hemopexin domain exchange with MT4-MMP blocks enzyme maturation and trafficking to the plasma membrane in MCF7 cells. Atkinson, S.J., Roghi, C., Murphy, G. Biochem. J. (2006) [Pubmed]
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