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Comparative genomics on Shisa orthologs

Yuriko Katoh1, Masaru Katoh

  • 1M&M Medical BioInformatics, Hongo 113-0033, Japan.

International Journal of Molecular Medicine
|June 9, 2005
PubMed

Insights

Researchers identified and characterized the rat Shisa (Tmem46) gene, revealing conserved domains crucial for WNT and FGF signaling pathways. This study provides insights into the molecular evolution of Shisa orthologs across vertebrates.

Area of Science:

  • Molecular Biology
  • Genomics
  • Proteomics

Background:

  • WNT and FGF signaling pathways are vital in development and implicated in human cancers like gastric and colorectal cancer.
  • Xenopus shisa is known to inhibit WNT and FGF receptor maturation, suggesting a role in regulating these pathways.

Purpose of the Study:

  • To identify and characterize the rat Shisa (Tmem46) gene.
  • To analyze the molecular evolution and conservation of Shisa orthologs across different species.

Main Methods:

  • Bioinformatics analyses including comparative proteomics and comparative genomics.
  • Sequence analysis of the rat Shisa gene and its encoded protein.
  • Comparison of Shisa orthologs from rat, mouse, human, chicken, Xenopus, and zebrafish.

Main Results:

  • The rat Shisa gene (Tmem46) was identified and located on chromosome 15p12, encoding a type I transmembrane protein.
  • High amino-acid identity was observed between rat Shisa and its mammalian orthologs (mouse, human).
  • Conserved domains (extracellular Cys-rich, C-terminal cytoplasmic) were identified, though promoter regions showed less conservation, suggesting functional divergence.

Conclusions:

  • This is the first report detailing the rat Shisa gene and its molecular evolution.
  • Functional divergence of human SHISA from Xenopus shisa is predicted due to evolutionary changes in both protein and promoter regions.
  • Understanding Shisa evolution provides insights into WNT and FGF pathway regulation in different species.

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