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Gene Review

GFM1  -  G elongation factor, mitochondrial 1

Homo sapiens

Synonyms: COXPD1, EF-Gmt, EFG, EFG1, EFGM, ...
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Disease relevance of GFM1

  • The EFG1-mutant patient had early-onset Leigh syndrome, whereas the EFTu-mutant patient had severe infantile macrocystic leukodystrophy with micropolygyria [1].
  • The region of the cDNA coding for the mature sequence of isoform 1 of human mitochondrial EF-G (EF-G1(mt)) has been cloned and expressed in Escherichia coli [2].
  • HMW hTGF purified from the pooled urine of several patients with malignant astrocytomas and HMW hEGF purified from normal control urine comigrated at Mr 33,000 [3].
  • In this study, we demonstrate that fusidic acid resistance in Staphylococcus aureus results from point mutations within the chromosomal fusA gene encoding EF-G [4].
  • Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks [5].

High impact information on GFM1

  • During the ribosomal translocation, the binding of elongation factor G (EF-G) to the pretranslocational ribosome leads to a ratchet-like rotation of the 30S subunit relative to the 50S subunit in the direction of the mRNA movement [6].
  • The reaction is promoted by elongation factor G (EF-G) and accelerated by GTP hydrolysis [7].
  • Our findings demonstrate a direct action of hEGF to enhance collecting duct IGF I gene expression in vitro [8].
  • Platelet-associated hEGF/UG may account for the mitogenic activity of serum in cell lines in which platelet-derived growth factor is not active [9].
  • The former hEGF/UG component was a high-molecular weight form that was cleaved into hEGF/UG by incubation with either mouse EGF/UG-associated arginine esterase or trypsin [9].

Chemical compound and disease context of GFM1

  • The opposite strand upstream from the EF-G coding locus revealed an open reading frame (ORF) encoding a polypeptide having 52.5% identity with an E. coli protein (the pdxJ gene product) involved in pyridoxine condensation [10].
  • Here we show that a conserved arginine, R29, of Escherichia coli EF-G is crucial for GTP hydrolysis on the ribosome, but not for GTP binding or ribosome interaction, suggesting that it may be directly involved in catalysis [11].
  • A specific two-site ELISA for human epidermal growth factor (hEGF) has been used to measure urinary hEGF/creatinine ratios in 30 normal subjects, 30 hospital in-patients with breast cancer and 30 hospital in-patients with colonic or rectal cancer [12].
  • In the salivary pleomorphic adenoma type of mixed tumour of the skin, luminal tumour cells of tubular and duct-like structures gave a very characteristic hEGF staining reaction [13].
  • We introduced a double-blind controlled clinical study to compare intravenous human epidermal growth factor (hEGF) to cetraxate hydrochloride (CH), an antiulcer drug, for their healing effect on gastric ulcers [14].

Biological context of GFM1


Anatomical context of GFM1

  • Apparently, the common characteristic of these GTPases is an extensive consensus structural unit that possibly accounts for a similar interaction with the ribosome and is composed of two domains homologous to the G domain and domain II in EF-Tu and EF-G [18].
  • In this study, using immunoaffinity chromatography to extract hEGF/UG from plasma, we found that immunoreactive hEGF/UG in blood was associated with blood platelets [9].
  • After the binding and degradation of 125I-hEGF the fibroblasts are no longer able to rebind fresh hormone [19].
  • Cells were cultured first in high-phosphate medium and then, for induction of the hEGF-encoding gene, transferred to low-phosphate medium containing Ahx (0.25 mg/ml). hEGF and Ahx-substituted hEGF, [Ahx21]hEGF, secreted into the periplasm were recovered [20].
  • This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle-mediated DNA transfer (Accell) [21].

Associations of GFM1 with chemical compounds

  • Translation of polyphenylalanine from a polyuridine template by the ribosome in the absence of the elongation factors EFG and EFTu (and the energy derived from GTP hydrolysis) is promoted by modification of the ribosome with thiol-specific reagents such as para-chloromercuribenzoate (pCMB) [22].
  • And, while Tet(M) and EF-G GTPase activities are tetracycline resistant, the two proteins differ in their sensitivities to fusidic acid, with the latter activity inhibited by the drug [23].
  • Furthermore, while Tet(M) protects translation from tetracycline inhibition in a defined system, it is unable to substitute for either EF-G or elongation factor Tu [23].
  • The elongation factor G (EF-Gchl) and elongation factor Tu (EF-Tuchl) present in spinach chloroplasts become labelled when isolated chloroplasts are incubated in the light with radioactive methionine [24].
  • A strain carrying one disrupted EFG1 allele and one EFG1 allele under the control of the glucose-repressible PCK1 promoter forms rod-like, pseudohyphal cells, but is unable to form true hyphae on glucose-containing media [25].

Other interactions of GFM1

  • Identification and characterization of two novel human mitochondrial elongation factor genes, hEFG2 and hEFG1, phylogenetically conserved through evolution [15].
  • Expression and characterization of isoform 1 of human mitochondrial elongation factor G [2].
  • Stimulation of the GTPase activity of translation elongation factor G by ribosomal protein L7/12 [26].
  • In the DHL-9 B cell line, this site was nonfunctional; however, we found a potential EGF-1/WT1 site located more 3' in a region of negative regulatory activity [27].
  • The VIIa light chain, specifically the Gla and EGF-1 domains, form extended hydrophobic contacts with TF which account for most of the free energy of binding [28].

Analytical, diagnostic and therapeutic context of GFM1


  1. Infantile Encephalopathy and Defective Mitochondrial DNA Translation in Patients with Mutations of Mitochondrial Elongation Factors EFG1 and EFTu. Valente, L., Tiranti, V., Marsano, R.M., Malfatti, E., Fernandez-Vizarra, E., Donnini, C., Mereghetti, P., De Gioia, L., Burlina, A., Castellan, C., Comi, G.P., Savasta, S., Ferrero, I., Zeviani, M. Am. J. Hum. Genet. (2007) [Pubmed]
  2. Expression and characterization of isoform 1 of human mitochondrial elongation factor G. Bhargava, K., Templeton, P., Spremulli, L.L. Protein Expr. Purif. (2004) [Pubmed]
  3. Human brain tumor-associated urinary high molecular weight transforming growth factor: a high molecular weight form of epidermal growth factor. Stromberg, K., Hudgins, W.R., Dorman, L.S., Henderson, L.E., Sowder, R.C., Sherrell, B.J., Mount, C.D., Orth, D.N. Cancer Res. (1987) [Pubmed]
  4. Molecular analysis of fusidic acid resistance in Staphylococcus aureus. Besier, S., Ludwig, A., Brade, V., Wichelhaus, T.A. Mol. Microbiol. (2003) [Pubmed]
  5. Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks. Setiadi, E.R., Doedt, T., Cottier, F., Noffz, C., Ernst, J.F. J. Mol. Biol. (2006) [Pubmed]
  6. Locking and unlocking of ribosomal motions. Valle, M., Zavialov, A., Sengupta, J., Rawat, U., Ehrenberg, M., Frank, J. Cell (2003) [Pubmed]
  7. An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation. Savelsbergh, A., Katunin, V.I., Mohr, D., Peske, F., Rodnina, M.V., Wintermeyer, W. Mol. Cell (2003) [Pubmed]
  8. Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor. Rogers, S.A., Miller, S.B., Hammerman, M.R. J. Clin. Invest. (1991) [Pubmed]
  9. Human plasma epidermal growth factor/beta-urogastrone is associated with blood platelets. Oka, Y., Orth, D.N. J. Clin. Invest. (1983) [Pubmed]
  10. Arrangement and nucleotide sequence of the gene (fus) encoding elongation factor G (EF-G) from the hyperthermophilic bacterium Aquifex pyrophilus: phylogenetic depth of hyperthermophilic bacteria inferred from analysis of the EF-G/fus sequences. Bocchetta, M., Ceccarelli, E., Creti, R., Sanangelantoni, A.M., Tiboni, O., Cammarano, P. J. Mol. Evol. (1995) [Pubmed]
  11. Arginines 29 and 59 of elongation factor G are important for GTP hydrolysis or translocation on the ribosome. Mohr, D., Wintermeyer, W., Rodnina, M.V. EMBO J. (2000) [Pubmed]
  12. Urinary epidermal growth factor (hEGF) levels in patients with carcinomas of the breast, colon and rectum. Sweetenham, J.W., Davies, D.E., Warnes, S., Alexander, P. Br. J. Cancer (1990) [Pubmed]
  13. Immunohistochemical localization by monoclonal antibody of human epidermal growth factor in mixed tumours of the skin. Noda, Y., Tsukitani, K., Oosumi, H., Kato, K., Hayashi, T., Mori, M. J. Cutan. Pathol. (1987) [Pubmed]
  14. Gastric ulcer treatment with intravenous human epidermal growth factor: a double-blind controlled clinical study. Itoh, M., Matsuo, Y. J. Gastroenterol. Hepatol. (1994) [Pubmed]
  15. Identification and characterization of two novel human mitochondrial elongation factor genes, hEFG2 and hEFG1, phylogenetically conserved through evolution. Hammarsund, M., Wilson, W., Corcoran, M., Merup, M., Einhorn, S., Grandér, D., Sangfelt, O. Hum. Genet. (2001) [Pubmed]
  16. The molecular basis for tissue specificity of the oxidative phosphorylation deficiencies in patients with mutations in the mitochondrial translation factor EFG1. Antonicka, H., Sasarman, F., Kennaway, N.G., Shoubridge, E.A. Hum. Mol. Genet. (2006) [Pubmed]
  17. Cloning and characterization of human and mouse mitochondrial elongation factor G, GFM and Gfm, and mapping of GFM to human chromosome 3q25.1-q26.2. Gao, J., Yu, L., Zhang, P., Jiang, J., Chen, J., Peng, J., Wei, Y., Zhao, S. Genomics (2001) [Pubmed]
  18. Structure-based sequence alignment of elongation factors Tu and G with related GTPases involved in translation. Avarsson, A. J. Mol. Evol. (1995) [Pubmed]
  19. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. Carpenter, G., Cohen, S. J. Cell Biol. (1976) [Pubmed]
  20. Biosynthesis of a protein containing a nonprotein amino acid by Escherichia coli: L-2-aminohexanoic acid at position 21 in human epidermal growth factor. Koide, H., Yokoyama, S., Kawai, G., Ha, J.M., Oka, T., Kawai, S., Miyake, T., Fuwa, T., Miyazawa, T. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  21. In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. Andree, C., Swain, W.F., Page, C.P., Macklin, M.D., Slama, J., Hatzis, D., Eriksson, E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  22. EFG-independent translocation of the mRNA:tRNA complex is promoted by modification of the ribosome with thiol-specific reagents. Southworth, D.R., Brunelle, J.L., Green, R. J. Mol. Biol. (2002) [Pubmed]
  23. Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent. Burdett, V. J. Bacteriol. (1996) [Pubmed]
  24. Chloroplast elongation factors are synthesized in the chloroplast. Ciferri, O., Di Pasquale, G., Tiboni, O. Eur. J. Biochem. (1979) [Pubmed]
  25. Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. Stoldt, V.R., Sonneborn, A., Leuker, C.E., Ernst, J.F. EMBO J. (1997) [Pubmed]
  26. Stimulation of the GTPase activity of translation elongation factor G by ribosomal protein L7/12. Savelsbergh, A., Mohr, D., Wilden, B., Wintermeyer, W., Rodnina, M.V. J. Biol. Chem. (2000) [Pubmed]
  27. Repression of the c-myb gene by WT1 protein in T and B cell lines. McCann, S., Sullivan, J., Guerra, J., Arcinas, M., Boxer, L.M. J. Biol. Chem. (1995) [Pubmed]
  28. The structural basis of function of the TF. VIIa complex in the cellular initiation of coagulation. Edgington, T.S., Dickinson, C.D., Ruf, W. Thromb. Haemost. (1997) [Pubmed]
  29. Aromaticity at position 37 in human epidermal growth factor is not obligatory for activity. Engler, D.A., Hauser, M.R., Cook, J.S., Niyogi, S.K. Mol. Cell. Biol. (1991) [Pubmed]
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