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Gene Review

IS2  -  Scoliosis, idiopathic 2

Homo sapiens

 
 
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Disease relevance of IS2

  • In vitro analysis of p94 autolysis showed that autolysis in IS1 proceeds without immediate disassembly into fragments and that the newly identified cryptic autolytic site in IS2 is critical for disassembling autolyzed fragments [1].
  • Despite this inconspicuous modification of the IS2 linker between domains III and IV, both patients developed signs and symptoms of the disease within their second decade of life [2].
  • Here we identified a sibling pair with LGMD2A-type muscular dystrophy caused by a homozygous Ser606Leu (S606L) substitution in the IS2 linker domain [2].
  • Limb girdle muscular dystrophy in a sibling pair with a homozygous Ser606Leu mutation in the alternatively spliced IS2 region of calpain 3 [2].
  • We have previously described temperature sensitive rho mutants of Escherichia coli (e.g., rho15) that are defective in transcription termination at various signals, including an IS2 DNA insertion in the gal operon [Das, A., Court, D. & Adhya, S. (1976) Proc. Natl. Acad. Sci. USA, 73, 1959-1963] [3].
 

High impact information on IS2

  • In this paper, we report the isolation of mutants altered in the beta subunit of RNA polymerase (a class of Rifampicin-resistant mutants), which restore gal IS2 polarity in the rho 15 strain [3].
  • This calcium-dependent cysteine protease resembles the large subunit of m-calpain but with three unique additional sequences: an N-terminal region (NS), and two insertions (IS1 and IS2) [4].
  • It is now shown that early intermediates, IS1 and IS2 as well as a late native-like intermediate, IN, are present on the folding pathways of US, and an early intermediate IF1 on the folding pathway of UF, when barstar is refolded in concentrations of GdnHCl below 2.0 M [5].
  • Introduction of a functional CadC restores cadaverine expression in all EIEC strains harboring either an IS2 element or a defective cadC promoter [6].
  • However, the analysis also revealed the presence of a new type of dimer, "e" (QS1 = 0.38 mm/s, IS1 = 0.51 mm/s and QS2 = 0.72 mm/s, IS2 = 0.50 mm/s), and this was also assigned to the ferroxidase center [7].
 

Biological context of IS2

 

Anatomical context of IS2

  • Therefore, 7 of the cell lines (Colo320, EB, Fri, IS2, IS3, SW480, and V9P) are here completely karyotyped for the first time and, among these, 5 have not previously been cytogenetically described [11].
 

Associations of IS2 with chemical compounds

  • DNA of the IS-elements IS1 and IS2 was prepared by digestion of appropriate heteroduplex molecules with endonuclease S1, followed by sucrose gradient centrifugation or gel electrophoresis [12].
  • Cortisol and two internal standards, 19-nortestosterone (IS1) and 6 alpha-methylprednisolone (IS2) are extracted with dichloromethane and analyzed on a C18 reversed-phase column eluted with a mobile phase of methanol:water at a flow rate of 0.75 ml/min [13].
  • These residues are located in the insertion sequence-2 (IS-2), which was conserved in six clones of the human MT2-MMP gene from different sources, except that of proline-183 which was substituted with serine from HT1080 cells [14].
 

Other interactions of IS2

  • Polyclonal antibodies were prepared against peptides whose sequences were taken from the three unique regions of human CAPN3, namely NS, IS1, and IS2, which are not found in other members of the calpain family [15].
 

Analytical, diagnostic and therapeutic context of IS2

  • In order to study the relationship between SCC-HN associated immunosuppression and retroviral p15E, we produced three new monoclonal antibodies (MAbs; ER-IS1, ER-IS2, and ER-IS5) directed against the immunosuppressive synthetic CKS-17 peptide [16].
  • DNA extracted from paraffin-embedded tissues was used directly for PCR amplification using primers IS1 and IS2 to amplify a 123 base pair (bp) region of IS6110, sjMT3 and sjMTr2 to amplify a 281 bp region of protein antigen b, and INS1 and INS2 to amplify a 245 bp region of IS986 [17].

References

  1. Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a genetic reporter system. Ono, Y., Torii, F., Ojima, K., Doi, N., Yoshioka, K., Kawabata, Y., Labeit, D., Labeit, S., Suzuki, K., Abe, K., Maeda, T., Sorimachi, H. J. Biol. Chem. (2006) [Pubmed]
  2. Limb girdle muscular dystrophy in a sibling pair with a homozygous Ser606Leu mutation in the alternatively spliced IS2 region of calpain 3. Jenne, D.E., Kley, R.A., Vorgerd, M., Schröder, J.M., Weis, J., Reimann, H., Albrecht, B., Nürnberg, P., Thiele, H., Müller, C.R., Meng, G., Witt, C.C., Labeit, S. Biol. Chem. (2005) [Pubmed]
  3. Interaction of RNA polymerase and rho in transcription termination: coupled ATPase. Das, A., Merril, C., Adhya, S. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  4. Insertion sequence 1 of muscle-specific calpain, p94, acts as an internal propeptide. Diaz, B.G., Moldoveanu, T., Kuiper, M.J., Campbell, R.L., Davies, P.L. J. Biol. Chem. (2004) [Pubmed]
  5. The folding mechanism of barstar: evidence for multiple pathways and multiple intermediates. Shastry, M.C., Udgaonkar, J.B. J. Mol. Biol. (1995) [Pubmed]
  6. CadC is the preferential target of a convergent evolution driving enteroinvasive Escherichia coli toward a lysine decarboxylase-defective phenotype. Casalino, M., Latella, M.C., Prosseda, G., Colonna, B. Infect. Immun. (2003) [Pubmed]
  7. Stages in iron storage in the ferritin of Escherichia coli (EcFtnA): analysis of Mössbauer spectra reveals a new intermediate. Bauminger, E.R., Treffry, A., Quail, M.A., Zhao, Z., Nowik, I., Harrison, P.M. Biochemistry (1999) [Pubmed]
  8. Detection of an IS2-encoded 46-kilodalton protein capable of binding terminal repeats of IS2. Hu, S.T., Lee, L.C., Lei, G.S. J. Bacteriol. (1996) [Pubmed]
  9. Evolution of poliovirus type I during 5.5 years of prolonged enteral replication in an immunodeficient patient. Bellmunt, A., May, G., Zell, R., Pring-Akerblom, P., Verhagen, W., Heim, A. Virology (1999) [Pubmed]
  10. Nucleotide sequence and expression in E. coli of the complete P4 type VP4 from a G2 serotype human rotavirus. Mahajan, N.P., Rao, C.D. Arch. Virol. (1996) [Pubmed]
  11. Genome signatures of colon carcinoma cell lines. Kleivi, K., Teixeira, M.R., Eknaes, M., Diep, C.B., Jakobsen, K.S., Hamelin, R., Lothe, R.A. Cancer Genet. Cytogenet. (2004) [Pubmed]
  12. The isolation of IS1 and IS2 DNA. Schmidt, F., Besemer, J., Starlinger, P. Mol. Gen. Genet. (1976) [Pubmed]
  13. Improved liquid chromatographic determination of serum cortisol with double internal standardization compared to radioimmunoassay and fluorometry, and evaluated by isotope dilution/mass spectrometry. Lambert, W.E., De Slypere, J.P., Jonckheere, J.A., Vermeulen, A., De Leenheer, A.P. Anal. Biochem. (1983) [Pubmed]
  14. Human membrane type-2 matrix metalloproteinase is defective in cell-associated activation of progelatinase A. Miyamori, H., Takino, T., Seiki, M., Sato, H. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  15. Purification and identification of two putative autolytic sites in human calpain 3 (p94) expressed in heterologous systems. Federici, C., Eshdat, Y., Richard, I., Bertin, B., Guillaume, J.L., Hattab, M., Beckmann, J.S., Strosberg, A.D., Camoin, L. Arch. Biochem. Biophys. (1999) [Pubmed]
  16. New monoclonal antibodies against the putative immunosuppressive site of retroviral p15E. Lang, M.S., Oostendorp, R.A., Simons, P.J., Boersma, W., Knegt, P., van Ewijk, W. Cancer Res. (1994) [Pubmed]
  17. Comparison of three different primer pairs for the detection of Mycobacterium tuberculosis by polymerase chain reaction in paraffin-embedded tissues. Ozkara, H.A., Kocagöz, T., Ozçelik, U., Akçören, Z., Göçmen, A. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. (1998) [Pubmed]
 
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