title: Sequence conserved for subcellular localization.
abstract: The more proteins diverged in sequence, the more difficult it becomes for bioinformatics to infer similarities of protein function and structure from sequence. The precise thresholds used in automated genome annotations depend on the particular aspect of protein function transferred by homology. Here, we presented the first large-scale analysis of the relation between sequence similarity and identity in subcellular localization. Three results stood out: (1) The subcellular compartment is generally more conserved than what might have been expected given that short sequence motifs like nuclear localization signals can alter the native compartment; (2) the sequence conservation of localization is similar between different compartments; and (3) it is similar to the conservation of structure and enzymatic activity. In particular, we found the transition between the regions of conserved and nonconserved localization to be very sharp, although the thresholds for conservation were less well defined than for structure and enzymatic activity. We found that a simple measure for sequence similarity accounting for pairwise sequence identity and alignment length, the HSSP distance, distinguished accurately between protein pairs of identical and different localizations. In fact, BLAST expectation values outperformed the HSSP distance only for alignments in the subtwilight zone. We succeeded in slightly improving the accuracy of inferring localization through homology by fine tuning the thresholds. Finally, we applied our results to the entire SWISS-PROT database and five entirely sequenced eukaryotes.
authors.affiliation: Columbia University Bioinformatics Center (CUBIC), Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Nair
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rost
mesh_terms: D000595:Amino Acid Sequence; D002477:Cells / Q000166:cytology / Q000378:metabolism*; D019295:Computational Biology; D017124:Conserved Sequence; D030562:Databases, Protein; D021382:Protein Sorting Signals; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D021382:Protein Sorting Signals; D011506:Proteins