Universal Evolutionary Trace

The structure and function of proteins underlie most aspects of biology and their mutational perturbations often cause disease. A central question is which protein residue positions are important and cluster to form functional sites.

As a solution to this question, the Evolutionary Trace (ET) computes the relative rank of functional and structural importance among protein homologs sequence positions. The rank is lower if sequence positions vary among evolutionarily closer homologs and higher if the positions vary among evolutionarily distant homologs. Thus, ET uses evolutionary distances as a proxy for functional distances to correlate genotype variations with phenotype, or fitness, variations. This approach identifies functional determinants, predicts function, guides the mutational redesign of functional and allosteric specificity, and interprets the action of coding sequence variations in proteins, people, and populations.

The UET (Universal Evolutionary Trace) database offers pre-computed ET analyses for the protein structure databank, and on-the-fly analysis of any UNIPROT or amino acid sequence in FASTA format. Additionally, ET results map to a structure through a JSmol display to identify functionally important regions.

Step 1: Choose the input method

Not sure how to use this service?

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You may upload your own multiple sequence alignment using the Advanced Options section in the next step(s).

Important note: The services and data in this website are intended for research purposes only, not for clinical and diagnostic use.

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Please cite the following reference for the UET server

Lua RC, Wilson SJ, Konecki DM, et al. UET: a database of evolutionarily-predicted functional determinants of protein sequences that cluster as functional sites in protein structures. Nucleic Acids Res. 2016;44(D1):D308-D312. doi: 10.1093/nar/gkv1279 PMID: 26590254.

Also consider citing the following references for Evolutionary Trace (ET):

Lichtarge O, Bourne HR, Cohen FE. An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol. 1996 Mar 29;257(2):342-58. doi: 10.1006/jmbi.1996.0167 PMID: 8609628.

Mihalek I, Res I, Lichtarge O. A family of evolution-entropy hybrid methods for ranking protein residues by importance. J Mol Biol. 2004 Mar 5;336(5):1265-82. doi: 10.1016/j.jmb.2003.12.078 PMID: 15037084.