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Chemical Compound Review

Thr-Gly     2-[[(2S,3S)-2-amino-3- hydroxy...

Synonyms: CHEMBL328594, AC1O531J
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Disease relevance of Thr-Gly

  • To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells [1].
  • The key component in the fusion is the catalytic core of sortase A from Staphylococcus aureus (SrtAc), which recognizes and cleaves the Thr-Gly bond at an LPXTG sequence with moderate activity [2].
  • Various tRNA transcripts were constructed to study the identity elements of E. coli tRNAs (Arg, Lys, Ala, Trp, Thr, Gly, Ser, Asn, Cys, His) [3].

High impact information on Thr-Gly

  • This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection [4].
  • The deletion changes the amino acid sequence at position 899 substituting Arg for a Thr-Gly [5].
  • In D. melanogaster, this region is replaced by a dipeptide Thr-Gly repeat, which plays a role in the thermal stability of the circadian phenotype [6].
  • The results are consistent with the view that selection may be operating on various haplotypes which share the Thr-Gly length alleles encoding 17, 20 and 23 dipeptide pairs, and that the repeat itself may be the focus for selection [7].
  • Consequently, the Thr-Gly repeat does not have a mutation rate that is as high as some of the non-coding minisatellites, but it is several orders of magnitude higher than the nucleotide substitution rate [7].

Biological context of Thr-Gly

  • Using chimeric per transgenes which carry the different species Thr-Gly fragments, we have been able to identify components of the behaviour that are modulated by this region of the PER protein [8].
  • It has previously been shown that Thr-Gly repeat length variation at the period gene affects song traits in D. melanogaster, which gives the repetitive regions a special interest [9].
  • In Drosophila simulans, balancing selection appears to maintain a polymorphism in this region, with three repeat lengths carrying 23, 24 or 25 Thr-Gly pairs, each in complete linkage disequilibrium with a distinctive flanking region amino acid moiety [10].

Associations of Thr-Gly with other chemical compounds

  • The study of amino acid repartition between liver and plasma with different diets indicates that transport could modulate utilization of Ala, Ser, Thr, Gly, Gln, and Asp [11].

Gene context of Thr-Gly

  • Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit [12].
  • N-Acetyl derivatives of Asn, Gln, Ser, Thr, Gly, Ala, Tyr, Pro, Met, Val, Ile and Leu as well as N-formyl-Met could be separated and identified in the same chromatographic run [13].
  • Clinal variation for repeat number in the Thr-Gly region of the period circadian timing gene in Drosophila melanogaster was described in Europe and has subsequently been used as evidence of thermal selection on period alleles [14].

Analytical, diagnostic and therapeutic context of Thr-Gly

  • The threonine-glycine (Thr-Gly) repeat region of the period (per) gene of eight natural populations of Drosophila simulans from Europe and North Africa was analyzed by polymerase chain reaction, DNA sequencing and heteroduplex formation [15].


  1. Formation of granular cytoplasmic aggregates in COS7 cells expressing mutant Cu/Zn superoxide dismutase associated with familial amyotrophic lateral sclerosis. Koide, T., Igarashi, S., Kikugawa, K., Nakano, R., Inuzuka, T., Yamada, M., Takahashi, H., Tsuji, S. Neurosci. Lett. (1998) [Pubmed]
  2. A self-cleavable sortase fusion for one-step purification of free recombinant proteins. Mao, H. Protein Expr. Purif. (2004) [Pubmed]
  3. In vitro study of E. coli tRNA identity elements. Tamura, T., Asahara, H., Nameki, N., Himeno, H., Hasegawa, T., Shimizu, M. Nucleic Acids Symp. Ser. (1992) [Pubmed]
  4. Natural variation in a Drosophila clock gene and temperature compensation. Sawyer, L.A., Hennessy, J.M., Peixoto, A.A., Rosato, E., Parkinson, H., Costa, R., Kyriacou, C.P. Science (1997) [Pubmed]
  5. Identification of an alternate type I insulin-like growth factor receptor beta subunit mRNA transcript. Yee, D., Lebovic, G.S., Marcus, R.R., Rosen, N. J. Biol. Chem. (1989) [Pubmed]
  6. Different period gene repeats take 'turns' at fine-tuning the circadian clock. Guantieri, V., Pepe, A., Zordan, M., Kyriacou, C.P., Costa, R., Tamburro, A.M. Proc. Biol. Sci. (1999) [Pubmed]
  7. Linkage disequilibrium, mutational analysis and natural selection in the repetitive region of the clock gene, period, in Drosophila melanogaster. Rosato, E., Peixoto, A.A., Costa, R., Kyriacou, C.P. Genet. Res. (1997) [Pubmed]
  8. Molecular analysis of circadian clocks in Drosophila simulans. Rogers, A.S., Rosato, E., Costa, R., Kyriacou, C.P. Genetica (2004) [Pubmed]
  9. Nucleotide and repeat length variation at the nonA gene of the Drosophila virilis group species and its effects on male courtship song. Huttunen, S., Vieira, J., Hoikkala, A. Genetica (2002) [Pubmed]
  10. A mutation in Drosophila simulans that lengthens the circadian period of locomotor activity. Rogers, A.S., Escher, S.A., Pasetto, C., Rosato, E., Costa, R., Kyriacou, C.P. Genetica (2004) [Pubmed]
  11. Fluxes and membrane transport of amino acids in rat liver under different protein diets. Fafournoux, P., Remesy, C., Demigne, C. Am. J. Physiol. (1990) [Pubmed]
  12. Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumors. Vitale, L., Lenzi, L., Huntsman, S.A., Canaider, S., Frabetti, F., Casadei, R., Facchin, F., Carinci, P., Zannotti, M., Coppola, D., Strippoli, P. Oncol. Rep. (2006) [Pubmed]
  13. Determination of free N-acetylamino acids in biological samples and N-terminal acetylamino acids of proteins. Kawakami, Y., Ohga, T., Shimamoto, C., Satoh, N., Ohmori, S. J. Chromatogr. (1992) [Pubmed]
  14. In search of clinal variation in the period and clock timing genes in Australian Drosophila melanogaster populations. Weeks, A.R., McKechnie, S.W., Hoffmann, A.A. J. Evol. Biol. (2006) [Pubmed]
  15. Molecular polymorphism in the period gene of Drosophila simulans. Rosato, E., Peixoto, A.A., Barbujani, G., Costa, R., Kyriacou, C.P. Genetics (1994) [Pubmed]
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