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Gene Review

lon  -  DNA-binding ATP-dependent protease La

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK0433, JW0429, capR, deg, dir, ...
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Disease relevance of lon

  • Pantolactone and butyrolactone, known to suppress cell filament formation in the lon mutant of Escherichia coli, were found also to be capable of partially correcting other anomalies of the mutant including impaired lysogenization with bacteriophages lambda and Pl and increased synthesis of colanic acid [1].
  • The nucleotide sequence of clpX, which is localized between the tig (trigger factor) and the lon (ATP-dependent protease) genes at 245 degrees on the standard Bacillus subtilis (Bs) genetic map, was determined [2].
  • Cloning, nucleotide sequencing, and expression of the Azospirillum brasilense lon gene: involvement in iron uptake [3].
  • The lon gene of Borrelia burgdorferi, encoding a homolog of the Lon protease, has been cloned and sequenced [4].
  • To characterize the function of the Lon protease within the Actinomycetales, a viable M. smegmatis Deltalon strain was constructed, demonstrating that lon is not essential under certain conditions [5].

High impact information on lon

  • The DNA sequence encoding a serine-type protease, similar to the lon protease gene of Escherichia coli, was cloned from the Arabidopsis genome [6].
  • Open reading frames corresponding in position and size to the umu and muc genes have been identified [7].
  • The fact that there was hybridization between the chromosome of the "cured" strain and a probe containing both muc genes but none when almost no mucB was present suggested that at least part of the mucB gene had been integrated into the Rec- chromosome [8].
  • The active site of a lon protease from Methanococcus jannaschii distinctly differs from the canonical catalytic Dyad of Lon proteases [9].
  • Mutations upstream of -35 had little effect, but alterations immediately upstream of -10 lowered basal transcription of a lon-lacZ operon fusion and reduced its response to inducers of the heat-shock response [10].

Chemical compound and disease context of lon


Biological context of lon


Anatomical context of lon

  • A disrupted mutant of lon was able to efficiently invade cultured epithelial cells and showed increased production and secretion of three identified SPI1 proteins, SipA, SipC, and SipD [18].

Associations of lon with chemical compounds

  • The most informative lon mutant overproduced capsular polysaccharide (RcsA stabilized) yet was resistant to DNA-damaging agents (SulA degraded) [17].
  • The mutant contains a single-base change within lon leading to a single amino acid change of glutamate 240 to lysine [17].
  • The degradation of abnormal canavanine-containing proteins is defective in clpA mutants especially in cells that also have a lon- mutation [19].
  • Introduction of the multicopy plasmid pZAQ containing the ftsZ gene, which is known to increase the level of FtsZ, suppressed the sensitivity of lon mutants to the DNA-damaging agents UV and nitrofurantoin [20].
  • Furthermore, the proteolytic responses to oxidative damage by menadione or H2O2 were almost identical in the isogenic strains RM312 (a K12 derivative) and RM1385 (a lon deletion mutant of RM312) [21].

Regulatory relationships of lon

  • The 5'-end of the B. burgdorferi lon gene appears to suppress the temperature-sensitive phenotype of an E. coli lpxA mutant [4].
  • The capR (lon) product controls expression of the gal operon independently of the galR repressor [22].

Other interactions of lon

  • The phenotypic suppression of a mutation in the gene rplX for ribosomal protein L24 by mutations affecting the lon gene product for protease LA in Escherichia coli K12 [14].
  • Extracts of clpA- lon- cells have ATP-dependent casein degrading activity [19].
  • An analysis of the degradation kinetics shows that Rep is a target of two protease systems: inactivation of either the clpP or lon gene results in a stabilization of Rep. Such a reaction scheme explains the counterintuitive observation that derepression is correlated with high repressor concentration [23].
  • An open reading frame homologous to the E. coli clpX gene was found in front of the lon gene [3].
  • Genetic studies using plasmid rescue techniques demonstrated that the lon gene is located very close to the 5' end of hupB and that the two genes are both transcribed clockwise on the E. coli map [Bachmann, Microbiol. Rev. 47 (1983) 180-230] [24].

Analytical, diagnostic and therapeutic context of lon

  • Site-directed mutagenesis of the -10 region of the lon promoter confirmed that the heat shock expression of the E. amylovora lon gene may be mediated by a sigma 32-like factor [25].
  • Our RT-PCR analysis revealed an elevation of expression of the oxyS gene in the lon mutant [26].
  • The results of Western blotting detected a decrease in the protein expression levels of BtuB and OmpF involved in colicin translocation in the lon mutant [26].
  • When protease La was isolated from R9 cells and from a recessive capR- strain using DEAE-cellulose chromatography, the mutant enzymes showed about 50% of the wild type activity [27].
  • Because of its high mean residue ellipticity ([theta] = 56 deg cm2 dmol-1 for the isolated holo-beta 2 subunit and 102 deg cm2 dmol-1 for the alpha 2-holo-beta 2 complex, respectively) the latter has been used to define different conformational states of the beta 2 dimer via CD titrations [28].


  1. Effects of pantolactone and butyrolactone on the pleiotropic phenotypes of lon mutants and on thermal induction of the SOS phenomena in a tif mutant of Escherichia coli K12. Nakayama, H., Nakayama, K., Nakayama, R., Kato, Y. Arch. Microbiol. (1982) [Pubmed]
  2. Sequence and transcriptional analysis of clpX, a class-III heat-shock gene of Bacillus subtilis. Gerth, U., Wipat, A., Harwood, C.R., Carter, N., Emmerson, P.T., Hecker, M. Gene (1996) [Pubmed]
  3. Cloning, nucleotide sequencing, and expression of the Azospirillum brasilense lon gene: involvement in iron uptake. Mori, E., Fulchieri, M., Indorato, C., Fani, R., Bazzicalupo, M. J. Bacteriol. (1996) [Pubmed]
  4. Cloning and expression of the Borrelia burgdorferi lon gene. Cloud, J.L., Marconi, R.T., Eggers, C.H., Garon, C.F., Tilly, K., Samuels, D.S. Gene (1997) [Pubmed]
  5. Species variation in ATP-dependent protein degradation: protease profiles differ between mycobacteria and protease functions differ between Mycobacterium smegmatis and Escherichia coli. Knipfer, N., Seth, A., Roudiak, S.G., Shrader, T.E. Gene (1999) [Pubmed]
  6. A cytoplasmic male sterility-associated mitochondrial peptide in common bean is post-translationally regulated. Sarria, R., Lyznik, A., Vallejos, C.E., Mackenzie, S.A. Plant Cell (1998) [Pubmed]
  7. umuDC and mucAB operons whose products are required for UV light- and chemical-induced mutagenesis: UmuD, MucA, and LexA proteins share homology. Perry, K.L., Elledge, S.J., Mitchell, B.B., Marsh, L., Walker, G.C. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  8. Genes from plasmid pKM101 in Haemophilus influenzae: separation of functions of mucA and mucB. Balganesh, M., Setlow, J.K. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  9. The active site of a lon protease from Methanococcus jannaschii distinctly differs from the canonical catalytic Dyad of Lon proteases. Im, Y.J., Na, Y., Kang, G.B., Rho, S.H., Kim, M.K., Lee, J.H., Chung, C.H., Eom, S.H. J. Biol. Chem. (2004) [Pubmed]
  10. Sequence of the lon gene in Escherichia coli. A heat-shock gene which encodes the ATP-dependent protease La. Chin, D.T., Goff, S.A., Webster, T., Smith, T., Goldberg, A.L. J. Biol. Chem. (1988) [Pubmed]
  11. The lonS gene regulates swarmer cell differentiation of Vibrio parahaemolyticus. Stewart, B.J., Enos-Berlage, J.L., McCarter, L.L. J. Bacteriol. (1997) [Pubmed]
  12. Overexpression of the hslVU operon suppresses SOS-mediated inhibition of cell division in Escherichia coli. Khattar, M.M. FEBS Lett. (1997) [Pubmed]
  13. IS186 insertion at a hot spot in the lon promoter as a basis for lon protease deficiency of Escherichia coli B: identification of a consensus target sequence for IS186 transposition. saiSree, L., Reddy, M., Gowrishankar, J. J. Bacteriol. (2001) [Pubmed]
  14. The phenotypic suppression of a mutation in the gene rplX for ribosomal protein L24 by mutations affecting the lon gene product for protease LA in Escherichia coli K12. Nishi, K., Schnier, J. Mol. Gen. Genet. (1988) [Pubmed]
  15. Controlled high-level expression of the lon gene of Escherichia coli allows overproduction of Lon protease. Thomas, C.D., Modha, J., Razzaq, T.M., Cullis, P.M., Rivett, A.J. Gene (1993) [Pubmed]
  16. lon incompatibility associated with mutations causing SOS induction: null uvrD alleles induce an SOS response in Escherichia coli. SaiSree, L., Reddy, M., Gowrishankar, J. J. Bacteriol. (2000) [Pubmed]
  17. A conserved domain in Escherichia coli Lon protease is involved in substrate discriminator activity. Ebel, W., Skinner, M.M., Dierksen, K.P., Scott, J.M., Trempy, J.E. J. Bacteriol. (1999) [Pubmed]
  18. The ATP-dependent lon protease of Salmonella enterica serovar Typhimurium regulates invasion and expression of genes carried on Salmonella pathogenicity island 1. Takaya, A., Tomoyasu, T., Tokumitsu, A., Morioka, M., Yamamoto, T. J. Bacteriol. (2002) [Pubmed]
  19. The two-component, ATP-dependent Clp protease of Escherichia coli. Purification, cloning, and mutational analysis of the ATP-binding component. Katayama, Y., Gottesman, S., Pumphrey, J., Rudikoff, S., Clark, W.P., Maurizi, M.R. J. Biol. Chem. (1988) [Pubmed]
  20. Overproduction of FtsZ suppresses sensitivity of lon mutants to division inhibition. Lutkenhaus, J., Sanjanwala, B., Lowe, M. J. Bacteriol. (1986) [Pubmed]
  21. Oxidatively denatured proteins are degraded by an ATP-independent proteolytic pathway in Escherichia coli. Davies, K.J., Lin, S.W. Free Radic. Biol. Med. (1988) [Pubmed]
  22. Regulation of galactose operon at the gal operator-promoter region in Escherichia coli K-12. Hua, S.S., Markovitz, A. J. Bacteriol. (1975) [Pubmed]
  23. Control of bacteriophage mu lysogenic repression. Ranquet, C., Toussaint, A., de Jong, H., Maenhaut-Michel, G., Geiselmann, J. J. Mol. Biol. (2005) [Pubmed]
  24. Genetic characterization of the gene hupB encoding the HU-1 protein of Escherichia coli. Kano, Y., Wada, M., Nagase, T., Imamoto, F. Gene (1986) [Pubmed]
  25. Cloning, expression, and characterization of the lon gene of Erwinia amylovora: evidence for a heat shock response. Eastgate, J.A., Taylor, N., Coleman, M.J., Healy, B., Thompson, L., Roberts, I.S. J. Bacteriol. (1995) [Pubmed]
  26. An E. coli lon mutant conferring partial resistance to colicin may reveal a novel role in regulating proteins involved in the translocation of colicin. Lee, Y.Y., Hu, H.T., Liang, P.H., Chak, K.F. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  27. Studies of the protein encoded by the lon mutation, capR9, in Escherichia coli. A labile form of the ATP-dependent protease La that inhibits the wild type protease. Chung, C.H., Waxman, L., Goldberg, A.L. J. Biol. Chem. (1983) [Pubmed]
  28. Circular dichroism studies on the interaction of tryptophan synthase with pyridoxal 5'-phosphate. Balk, H., Merkl, I., Bartholmes, P. Biochemistry (1981) [Pubmed]
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