RT Journal A1 Binkley, Jonathan A1 Karra, Kalpana A1 Kirby, Andrew A1 Hosobuchi, Midori A1 Stone, Eric A. A1 Sidow, Arend T1 ProPhylER: A curated online resource for protein function and structure based on evolutionary constraint analyses JF Genome Research JO Genome Research YR 2010 FD January 01 VO 20 IS 1 SP 142 OP 154 DO 10.1101/gr.097121.109 UL http://genome.cshlp.org/content/20/1/142.abstract AB ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated proteome resource that uses comparative sequence analysis to predict constraint and mutation impact for eukaryotic proteins. Its purpose is to inform any research program for which protein function and structure are relevant, by the predictive power of evolutionary constraint analyses. ProPhylER currently has nearly 9000 clusters of related proteins, including more than 200,000 sequences. It serves data via two interfaces. The “ProPhylER Interface” displays predictive analyses in sequence space; the “CrystalPainter” maps evolutionary constraints onto solved protein structures. Here we summarize ProPhylER's data content and analysis pipeline, demonstrate the use of ProPhylER's interfaces, and evaluate ProPhylER's unique regional analysis of evolutionary constraint. The high accuracy of ProPhylER's regional analysis complements the high resolution of its single-site analysis to effectively guide and inform structure–function investigations and predict the impact of polymorphisms.