UET: a database of evolutionarily-predicted functional determinants of protein sequences that cluster as functional sites in protein structures

作者: Rhonald C. Lua , Stephen J. Wilson , Daniel M. Konecki , Angela D. Wilkins , Eric Venner

DOI: 10.1093/NAR/GKV1279

关键词: BiologyDatabaseSequence (medicine)Protein structureOpen reading frameFunction (biology)PhenotypePeptide sequenceProtein sequencingCoding region

摘要: The structure and function of proteins underlie most aspects biology their mutational perturbations often cause disease. To identify the molecular determinants as well targets for drugs, it is central to characterize important residues how they cluster form functional sites. Evolutionary Trace (ET) achieves this by ranking structural importance protein sequence positions. ET uses evolutionary distances estimate correlates genotype variations with those in fitness phenotype. Thus, ranks are worse positions that vary among evolutionarily closer homologs but better mostly distant homologs. This approach identifies determinants, predicts function, guides redesign allosteric specificity, interprets action coding proteins, people populations. Now, UET database offers pre-computed analyses databank, on-the-fly analysis any sequence. A web interface retrieves rankings maps results a functionally regions. integrates several ways viewing on or can be found at http://mammoth.bcm.tmc.edu/uet/.

参考文章(37)
Angela Wilkins, Serkan Erdin, Rhonald Lua, Olivier Lichtarge, Evolutionary trace for prediction and redesign of protein functional sites. Methods of Molecular Biology. ,vol. 819, pp. 29- 42 ,(2012) , 10.1007/978-1-61779-465-0_3
Sean M. Peterson, Thomas F. Pack, Angela D. Wilkins, Nikhil M. Urs, Daniel J. Urban, Caroline E. Bass, Olivier Lichtarge, Marc G. Caron, Elucidation of G-protein and β-arrestin functional selectivity at the dopamine D2 receptor Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 7097- 7102 ,(2015) , 10.1073/PNAS.1502742112
A. D. Wilkins, R. Lua, S. Erdin, R. M. Ward, O. Lichtarge, Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation Protein Science. ,vol. 19, pp. 1296- 1311 ,(2010) , 10.1002/PRO.406
Panagiotis Katsonis, Amanda Koire, Stephen Joseph Wilson, Teng-Kuei Hsu, Rhonald C. Lua, Angela Dawn Wilkins, Olivier Lichtarge, Single nucleotide variations: Biological impact and theoretical interpretation Protein Science. ,vol. 23, pp. 1650- 1666 ,(2014) , 10.1002/PRO.2552
Hye Jin Kang, Angela D. Wilkins, Olivier Lichtarge, Theodore G. Wensel, Determinants of endogenous ligand specificity divergence among metabotropic glutamate receptors. Journal of Biological Chemistry. ,vol. 290, pp. 2870- 2878 ,(2015) , 10.1074/JBC.M114.622233
David M. Neskey, Abdullah A. Osman, Thomas J. Ow, Panagiotis Katsonis, Thomas McDonald, Stephanie C. Hicks, Teng-Kuei Hsu, Curtis R. Pickering, Alexandra Ward, Ameeta Patel, John S. Yordy, Heath D. Skinner, Uma Giri, Daisuke Sano, Michael D. Story, Beth M. Beadle, Adel K. El-Naggar, Merrill S. Kies, William N. William, Carlos Caulin, Mitchell Frederick, Marek Kimmel, Jeffrey N. Myers, Olivier Lichtarge, Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer Cancer Research. ,vol. 75, pp. 1527- 1536 ,(2015) , 10.1158/0008-5472.CAN-14-2735
Tim Clackson, Mark H. Ultsch, James A. Wells, Abraham M. de Vos, Structural and functional analysis of the 1:1 growth hormone:receptor complex reveals the molecular basis for receptor affinity. Journal of Molecular Biology. ,vol. 277, pp. 1111- 1128 ,(1998) , 10.1006/JMBI.1998.1669
T. Gaj, A. C. Mercer, C. A. Gersbach, R. M. Gordley, C. F. Barbas, Structure-guided reprogramming of serine recombinase DNA sequence specificity Proceedings of the National Academy of Sciences of the United States of America. ,vol. 108, pp. 498- 503 ,(2011) , 10.1073/PNAS.1014214108
L. Oliveira, A. C. M. Paiva, G. Vriend, Correlated Mutation Analyses on Very Large Sequence Families ChemBioChem. ,vol. 3, pp. 1010- 1017 ,(2002) , 10.1002/1439-7633(20021004)3:10<1010::AID-CBIC1010>3.0.CO;2-T