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Related Experiment Videos

Sequence conserved for subcellular localization.

Rajesh Nair1, Burkhard Rost

  • 1Columbia University Bioinformatics Center (CUBIC), Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.

Protein Science : a Publication of the Protein Society
|November 21, 2002
PubMed
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Protein sequence similarity accurately predicts subcellular localization, even with low sequence identity. Bioinformatics tools can improve predictions by fine-tuning thresholds for inferring protein function and location.

Area of Science:

  • Computational Biology
  • Bioinformatics
  • Proteomics

Background:

  • Inferring protein function and structure from sequence similarity becomes challenging as sequences diverge.
  • Automated genome annotation thresholds vary depending on the specific protein function being transferred via homology.

Purpose of the Study:

  • To conduct the first large-scale analysis of the relationship between sequence similarity and protein subcellular localization.
  • To evaluate the accuracy of different sequence similarity measures in predicting protein localization.

Main Methods:

  • Analyzed the correlation between sequence similarity (identity and alignment length) and subcellular localization across large protein datasets.
  • Compared the performance of HSSP distance and BLAST expectation values for predicting localization.

Related Experiment Videos

  • Fine-tuned prediction thresholds to improve accuracy.
  • Main Results:

    • Subcellular localization is generally more conserved than anticipated, with short motifs capable of altering native compartments.
    • Sequence conservation of localization is consistent across different cellular compartments and comparable to structure and enzymatic activity conservation.
    • HSSP distance accurately distinguished between identical and different localizations; BLAST expectation values were superior only in specific low-similarity ranges.

    Conclusions:

    • Protein sequence similarity is a reliable indicator of subcellular localization, with a sharp transition between conserved and non-conserved regions.
    • Fine-tuning thresholds can enhance the accuracy of inferring protein localization through homology.
    • The findings were validated across the SWISS-PROT database and five fully sequenced eukaryotes.