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Gene Review

LMLN  -  leishmanolysin-like (metallopeptidase M8...

Homo sapiens

Synonyms: GP63, Gp63, INV, IX14, Invadolysin, ...
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Disease relevance of LMLN

  • Southern hybridization analysis of the alpha-galactosidase gene in affected hemizygous males from 130 unrelated families with Fabry disease revealed six with different gene rearrangements and one with an exonic point mutation resulting in the obliteration of an Msp I restriction site [1].
  • HBV DNA from virions (Dane particles) and virus-infected liver tissue was digested with Hpa II or Msp I and fractionated by electrophoresis in agarose gels, and the restriction enzyme cleavage pattern was examined by Southern blot analysis [2].
  • The methylation of various hepatitis B virus (HBV) DNA sequences was examined using the restriction endonucleases Hpa II and Msp I [2].
  • Analysis of the genome indicates a number of potential virulence factors including a family of 12 proteins related to the Msp protein of Treponema denticola, a number of putative hemolysins, as well as several other classes of proteins of interest [3].
  • 5. Dramatic K+ depletion in response to ammonia additions at pH 8.0 occurred with Ms. barkeri, another strain of Msp. hungatei, Escherichia coli, and Bacillus polymyxa [4].

Psychiatry related information on LMLN


High impact information on LMLN

  • The cytosines in the CpG sequence are known to be frequently methylated in mammals, and the occurrence of significant variation in Msp I and Taq I sites supports the view that methylated cytosine residues are hotspots for mutation in mammalian DNA [7].
  • In both rat and human chromosomes, regions containing amplified ribosomal RNA genes were specifically removed by the restriction endonuclease Msp I [8].
  • Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced [9].
  • A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the MspI site around codon 4046 in exon 29 of the APOB gene [9].
  • Restriction fragment length polymorphisms (RFLP) of the gene coding for apo B were identified using the endonucleases Xba I, Eco RI, and Msp I in a group of 19 subjects with moderate hyperlipidemia [10].

Chemical compound and disease context of LMLN

  • Whereas Msp B caused a burst effect (hypoglycemia) followed by quick change in blood glucose and insulin level, Msp A exhibited relatively sustained release of insulin and blood glucose level for at least 10 days [11].
  • The presence of ACC and other mutations at codon 315 in the katG gene was detected by PCR amplification followed by restriction fragment length polymorphism (PCR-RFLP) generated with restriction enzymes Msp I and MspA1 I in 37 isoniazid-resistant and 22-susceptible Mycobacterium tuberculosis isolates from Kuwait obtained in 2001 [12].

Biological context of LMLN

  • Among Caucasians, the gene frequencies were 0.04/0.96 for Msp I/5', 0.43/0.57 for Hae III/3', 0.44/0.56 for Hae III/5', and 0.04/0.42/0.54 for Pst I/5'. These common variants provide a marker for chromosome 4 (q11-q13) [13].
  • Four midgene Msp I/Hpa II sites exhibit a progressive loss of methyl groups unrelated to changes in mu-chain gene expression, whereas a Msp I/Hpa II site and two Hha I sites surrounding the exon encoding the carboxyl terminus of the secreted form of mu chain (mus) become undermethylated during the transition to IgM secretion [14].
  • The analyses showed that a single Msp I/Hpa II site 5' to the immunoglobulin enhancer becomes undermethylated with the onset of mu-chain gene transcription [14].
  • The examination of the haplotype inter-relationships with PC-493 and the Msp I polymorphism 5' to the protein C gene established that PC-493 gave a 16.7% chance of new information per individual for people who were previously homozygous for the Msp I polymorphism [15].
  • Evaluation of the methylation status of the bcl-2 gene using the isoschizomers Msp I and Hpa II, and a probe corresponding to the first major exon of the gene showed complete demethylation of both copies of the bcl-2 gene in a region corresponding to a 2.4-kb Msp I fragment in all 20 cases of B-CLL [16].

Anatomical context of LMLN

  • Knowledge that this alteration creates a restriction site polymorphism for Msp I/Hpa II in the H-ras protooncogene made it possible to survey for the presence of the activated H-ras allele in normal cells as well as in clonally derived tumor cell lines of the same patient [17].
  • Two CCGG sites, at homologous positions 54 nucleotides in front of the G gamma- and A gamma-globin genes respectively, are not cleaved by Msp I in DNA from several human tissues, although DNA from placenta, foetal liver and from some established cell lines is cut at these sites [18].
  • In fact, HLA-DR alpha appears to be fully unmethylated at Msp I/Hpa II sites in K562 cells, not expressing DR molecules, and to exhibit a high degree of methylation in Colo 38 cells, which actively transcribe the gene [19].
  • Restriction digestion was performed using Taq I and Msp I, with the patient's lymphocyte DNA as controls [20].
  • STUDY DESIGN: Genomic deoxyribonucleic acid from leukocytes and sperm cells of 35 male subjects was analyzed by denaturing gradient gel electrophoresis after digestion by 4-bp site enzymes and Msp I and its methylation-sensitive isoschizomer Hpa II [21].

Associations of LMLN with chemical compounds

  • Digestion of DNA from these children with Msp I and Taq I, enzymes recognizing CpG dinucleotides, identified three different mutations, each correlating with expression of a different mutant enzyme [22].
  • In the course of our investigation, we identified another mutation in the same exon: a 3-bp in-frame deletion that eliminates one of two isoleucine codons immediately preceding the Msp I site [23].
  • Structures of the N-linked oligosaccharides of Gp63, the major surface glycoprotein, from Leishmania mexicana amazonensis [24].
  • In a multiple regression model for patients, Msp I genotype, cholesterol, and smoking remained as independent predictors of FVII:C levels, accounting for 32% of interindividual variation [25].
  • There were no significant differences in Factor VII:C levels or FVII Msp I gene polymorphism (Arg-Gln 353) R353Q genotype frequency between the groups [26].

Analytical, diagnostic and therapeutic context of LMLN

  • Restriction mapping identified two novel Msp I fragments derived from the 5' and 3' portions of the GPHe(Sta) gene, respectively [27].
  • PCR conditions were optimized to minimize PCR error using perfect match primers at the Msp I site in the p53 tumor suppressor gene at codon 248 [28].
  • Codigestion of the RT-PCR product with Msp I+Hpa I also resulted in 175- and 259-bp fragments [29].
  • METHODS: Microspheres of the triblock copolymer PLGA-PEG-PLGA were prepared in an aqueous-based method without using methylene chloride (Msp A) [11].
  • Genomic DNA from peripheral blood leucocytes of 23 unrelated DLA-D homozygous dogs representing nine DLA-D types (defined by mixed leucocyte reaction) was digested with restriction enzymes (BamHI, EcoRI, Hind III, Pvu II, Taq I, Rsa I, Msp I, Pst I and Bgl II), separated by agarose gel electrophoresis and transferred onto Biotrace membrane [30].


  1. Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene. Bernstein, H.S., Bishop, D.F., Astrin, K.H., Kornreich, R., Eng, C.M., Sakuraba, H., Desnick, R.J. J. Clin. Invest. (1989) [Pubmed]
  2. Integrated hepatitis B virus DNA sequences specifying the major viral core polypeptide are methylated in PLC/PRF/5 cells. Miller, R.H., Robinson, W.S. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  3. The genome of Treponema pallidum: new light on the agent of syphilis. Weinstock, G.M., Hardham, J.M., McLeod, M.P., Sodergren, E.J., Norris, S.J. FEMS Microbiol. Rev. (1998) [Pubmed]
  4. Ammonia/potassium exchange in methanogenic bacteria. Sprott, G.D., Shaw, K.M., Jarrell, K.F. J. Biol. Chem. (1984) [Pubmed]
  5. The Bal I and Msp I polymorphisms in the dopamine D3 receptor gene display, linkage disequilibrium with each other but no association with Tourette syndrome. Devor, E.J., Dill-Devor, R.M., Magee, H.J. Psychiatr. Genet. (1998) [Pubmed]
  6. Interactive Effects Between CYP1A1 Genotypes and Environmental Polychlorinated Dibenzo-p-Dioxins and Dibenzofurans Exposures on Liver Function Profile. Chen, H.L., Su, H.J., Wang, Y.J., Guo, Y.L., Liao, P.C., Lee, C.C. Journal of toxicology and environmental health. Part A. (2006) [Pubmed]
  7. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Barker, D., Schafer, M., White, R. Cell (1984) [Pubmed]
  8. Chromosome localization of highly repetitive human DNA's and amplified ribosomal DNA with restriction enzymes. Miller, D.A., Choi, Y.C., Miller, O.J. Science (1983) [Pubmed]
  9. Apolipoprotein B-100 Hopkins (arginine4019----tryptophan). A new apolipoprotein B-100 variant in a family with premature atherosclerosis and hyperapobetalipoproteinemia. Ladias, J.A., Kwiterovich, P.O., Smith, H.H., Miller, M., Bachorik, P.S., Forte, T., Lusis, A.J., Antonarakis, S.E. JAMA (1989) [Pubmed]
  10. Catabolic rate of low density lipoprotein is influenced by variation in the apolipoprotein B gene. Demant, T., Houlston, R.S., Caslake, M.J., Series, J.J., Shepherd, J., Packard, C.J., Humphries, S.E. J. Clin. Invest. (1988) [Pubmed]
  11. Biodegradable triblock copolymer microspheres based on thermosensitive sol-gel transition. Kwon, Y.M., Kim, S.W. Pharm. Res. (2004) [Pubmed]
  12. Contribution of AGC to ACC and other mutations at codon 315 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East. Ahmad, S., Mokaddas, E. Int. J. Antimicrob. Agents (2004) [Pubmed]
  13. Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia. Murray, J.C., Demopulos, C.M., Lawn, R.M., Motulsky, A.G. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  14. Specific 5' and 3' regions of the mu-chain gene are undermethylated at distinct stages of B-cell differentiation. Blackman, M.A., Koshland, M.E. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  15. Genotype establishments for protein C deficiency by use of a DNA polymorphism in the gene. Yamamoto, K., Tanimoto, M., Matsushita, T., Kagami, K., Sugiura, I., Hamaguchi, M., Takamatsu, J., Saito, H. Blood (1991) [Pubmed]
  16. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Hanada, M., Delia, D., Aiello, A., Stadtmauer, E., Reed, J.C. Blood (1993) [Pubmed]
  17. A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient. Kraus, M.H., Yuasa, Y., Aaronson, S.A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  18. A novel type of secondary modification of two CCGG residues in the human gamma delta beta-globin gene locus. van der Ploeg, L.H., Groffen, J., Flavell, R.A. Nucleic Acids Res. (1980) [Pubmed]
  19. Lack of correlation between hypomethylation and expression of the HLA-DR alpha gene. Gambari, R., Del Senno, L., Barbieri, R., Buzzoni, D., Gustafsson, K., Giacomini, P., Natali, P.G. Eur. J. Immunol. (1986) [Pubmed]
  20. Loss of c-met protooncogene in primary and metastatic sites of breast cancer. Ng, E.H., Pey, H.B., Law, H.Y., Ng, I., Ji, C.Y., Lin, V., Soo, K.C. Ann. Surg. Oncol. (1997) [Pubmed]
  21. Methylation-dependent melting polymorphisms in genomic fragments of deoxyribonucleic acid. Reindollar, R.H., Fusaris, K.W., Gray, M.R. Am. J. Obstet. Gynecol. (2000) [Pubmed]
  22. Hot spot mutations in adenosine deaminase deficiency. Hirschhorn, R., Tzall, S., Ellenbogen, A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  23. An unusual insertion/deletion in the gene encoding the beta-subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia. Tahara, T., Kraus, J.P., Rosenberg, L.E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  24. Structures of the N-linked oligosaccharides of Gp63, the major surface glycoprotein, from Leishmania mexicana amazonensis. Olafson, R.W., Thomas, J.R., Ferguson, M.A., Dwek, R.A., Chaudhuri, M., Chang, K.P., Rademacher, T.W. J. Biol. Chem. (1990) [Pubmed]
  25. Polymorphisms of the factor VII gene and circulating FVII:C levels in relation to acute cerebrovascular disease and poststroke mortality. Heywood, D.M., Carter, A.M., Catto, A.J., Bamford, J.M., Grant, P.J. Stroke (1997) [Pubmed]
  26. Coagulation factor VII activity, Arg/Gln353 polymorphism and features of insulin resistance in first-degree-relatives of South Asian patients with stroke. Kain, K., Catto, A.J., Young, J., Bamford, J., Bavington, J., Grant, P.J. Thromb. Haemost. (2002) [Pubmed]
  27. Glycophorin He(Sta) of the human red blood cell membrane is encoded by a complex hybrid gene resulting from two recombinational events. Huang, C.H., Lomas, C., Daniels, G., Blumenfeld, O.O. Blood (1994) [Pubmed]
  28. Nucleotide analogs and new buffers improve a generalized method to enrich for low abundance mutations. Day, J.P., Hammer, R.P., Bergstrom, D., Barany, F. Nucleic Acids Res. (1999) [Pubmed]
  29. Human fallopian tube as an extraovarian source of relaxin: messenger ribonucleic acid expression and cellular localization of immunoreactive protein and 125I-relaxin binding sites. Tang, X.M., Chegini, N. Biol. Reprod. (1995) [Pubmed]
  30. Characterization of class II alpha genes and DLA-D region allelic associations in the dog. Sarmiento, U.M., Storb, R.F. Tissue Antigens (1988) [Pubmed]
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