{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:26:26Z","timestamp":1775766386372,"version":"3.50.1"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T00:00:00Z","timestamp":1392249600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003470","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T21:47:50Z","timestamp":1392328070000},"page":"e1003470","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":66,"title":["The Structural Pathway of Interleukin 1 (IL-1) Initiated Signaling Reveals Mechanisms of Oncogenic Mutations and SNPs in Inflammation and Cancer"],"prefix":"10.1371","volume":"10","author":[{"given":"Saliha Ece","family":"Acuner Ozbabacan","sequence":"first","affiliation":[]},{"given":"Attila","family":"Gursoy","sequence":"additional","affiliation":[]},{"given":"Ruth","family":"Nussinov","sequence":"additional","affiliation":[]},{"given":"Ozlem","family":"Keskin","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2014,2,13]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1471-4906(01)02034-8","article-title":"Annotating genes with potential roles in the immune system: six new members of the IL-1 family","volume":"22","author":"E Dunn","year":"2001","journal-title":"Trends Immunol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"5411","DOI":"10.4049\/jimmunol.178.9.5411","article-title":"Cloning IL-1 and the birth of a new era in cytokine biology","volume":"178","author":"TT Pizarro","year":"2007","journal-title":"J Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S1471-4906(01)02040-3","article-title":"A new nomenclature for IL-1-family genes","volume":"22","author":"JE Sims","year":"2001","journal-title":"Trends Immunol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.immunol.021908.132715","article-title":"The inflammasomes: guardians of the body","volume":"27","author":"F Martinon","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1001\/archderm.144.3.392","article-title":"Autoinflammatory diseases: clinical and genetic advances","volume":"144","author":"S Farasat","year":"2008","journal-title":"Arch Dermatol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095","article-title":"Biologic basis for interleukin-1 in disease","volume":"87","author":"CA Dinarello","year":"1996","journal-title":"Blood"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"CA Dinarello","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"ref8","first-page":"cm1","article-title":"Interleukin-1 (IL-1) pathway","volume":"3","author":"A Weber","year":"2010","journal-title":"Sci Signal"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"13757","DOI":"10.1074\/jbc.270.23.13757","article-title":"Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex","volume":"270","author":"SA Greenfeder","year":"1995","journal-title":"J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1074\/mcp.M600455-MCP200","article-title":"Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components","volume":"6","author":"C Brikos","year":"2007","journal-title":"Mol Cell Proteomics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1073\/pnas.082100399","article-title":"IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase","volume":"99","author":"S Li","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/ni.1606","article-title":"Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2","volume":"9","author":"T Kawagoe","year":"2008","journal-title":"Nat Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/383443a0","article-title":"TRAF6 is a signal transducer for interleukin-1","volume":"383","author":"Z Cao","year":"1996","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1126\/science.271.5252.1128","article-title":"IRAK: a kinase associated with the interleukin-1 receptor","volume":"271","author":"Z Cao","year":"1996","journal-title":"Science"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/35065000","article-title":"Mammalian MAP kinase signalling cascades","volume":"410","author":"L Chang","year":"2001","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1038\/sj.onc.1210410","article-title":"Role of mitogen-activated protein kinase kinase 4 in cancer","volume":"26","author":"AJ Whitmarsh","year":"2007","journal-title":"Oncogene"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrc2694","article-title":"Signal integration by JNK and p38 MAPK pathways in cancer development","volume":"9","author":"EF Wagner","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1128\/MCB.05562-11","article-title":"Map2k4 functions as a tumor suppressor in lung adenocarcinoma and inhibits tumor cell invasion by decreasing peroxisome proliferator-activated receptor gamma2 expression","volume":"31","author":"YH Ahn","year":"2011","journal-title":"Mol Cell Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nature05610","article-title":"Patterns of somatic mutation in human cancer genomes","volume":"446","author":"C Greenman","year":"2007","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1126\/science.1164368","article-title":"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses","volume":"321","author":"S Jones","year":"2008","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s100380170086","article-title":"The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors","volume":"46","author":"S Yoshida","year":"2001","journal-title":"J Hum Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/nrc1503","article-title":"Targeting the mitogen-activated protein kinase cascade to treat cancer","volume":"4","author":"JS Sebolt-Leopold","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature04870","article-title":"Nuclear factor-kappaB in cancer development and progression","volume":"441","author":"M Karin","year":"2006","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"A Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.critrevonc.2008.07.021","article-title":"Infections and cancer: established associations and new hypotheses","volume":"70","author":"C de Martel","year":"2009","journal-title":"Crit Rev Oncol Hematol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"SI Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nmeth.2289","article-title":"Interactome3D: adding structural details to protein networks","volume":"10","author":"R Mosca","year":"2013","journal-title":"Nat Methods"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nbt.2106","article-title":"Three-dimensional reconstruction of protein networks provides insight into human genetic disease","volume":"30","author":"X Wang","year":"2012","journal-title":"Nat Biotechnol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/ng.462","article-title":"Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels","volume":"41","author":"JC Chambers","year":"2009","journal-title":"Nat Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1093\/nar\/gkr407","article-title":"Predicting the functional impact of protein mutations: application to cancer genomics","volume":"39","author":"B Reva","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/embor.2011.261","article-title":"Large-scale mapping of human protein interactome using structural complexes","volume":"13","author":"M Tyagi","year":"2012","journal-title":"EMBO Rep"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nature11503","article-title":"Structure-based prediction of protein-protein interactions on a genome-wide scale","volume":"490","author":"QC Zhang","year":"2012","journal-title":"Nature"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2006 0015","DOI":"10.1038\/msb4100057","article-title":"A comprehensive map of the toll-like receptor signaling network","volume":"2","author":"K Oda","year":"2006","journal-title":"Mol Syst Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/nar\/gkg089","article-title":"TRANSPATH: an integrated database on signal transduction and a tool for array analysis","volume":"31","author":"M Krull","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1107\/S0907444902003451","article-title":"The Protein Data Bank","volume":"58","author":"HM Berman","year":"2002","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jsb.2012.02.002","article-title":"Enriching the human apoptosis pathway by predicting the structures of protein-protein complexes","volume":"179","author":"SE Acuner Ozbabacan","year":"2012","journal-title":"J Struct Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1093\/bioinformatics\/bti443","article-title":"Prediction of protein-protein interactions by combining structure and sequence conservation in protein interfaces","volume":"21","author":"AS Aytuna","year":"2005","journal-title":"Bioinformatics"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"W331","DOI":"10.1093\/nar\/gki585","article-title":"PRISM: protein interactions by structural matching","volume":"33","author":"U Ogmen","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/nprot.2011.367","article-title":"Predicting protein-protein interactions on a proteome scale by matching evolutionary and structural similarities at interfaces using PRISM","volume":"6","author":"N Tuncbag","year":"2011","journal-title":"Nat Protoc"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/humu.21656","article-title":"Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs","volume":"33","author":"A David","year":"2012","journal-title":"Hum Mutat"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"32662","DOI":"10.1074\/jbc.M304229200","article-title":"A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates","volume":"278","author":"DT Ho","year":"2003","journal-title":"J Biol Chem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"ra74","DOI":"10.1126\/scisignal.2003004","article-title":"Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove","volume":"5","author":"A Garai","year":"2012","journal-title":"Sci Signal"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"16988","DOI":"10.1074\/jbc.274.24.16988","article-title":"Phosphorylation of MAP kinases by MAP\/ERK involves multiple regions of MAP kinases","volume":"274","author":"JL Wilsbacher","year":"1999","journal-title":"J Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"5038","DOI":"10.1038\/sj.onc.1205593","article-title":"Elevated JNK activation contributes to the pathogenesis of human brain tumors","volume":"21","author":"MA Antonyak","year":"2002","journal-title":"Oncogene"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1002\/humu.22145","article-title":"Oncogenic potential is related to activating effect of cancer single and double somatic mutations in receptor tyrosine kinases","volume":"33","author":"K Hashimoto","year":"2012","journal-title":"Hum Mutat"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/protein\/6.5.535","article-title":"Structure-Function Analysis of Human Il-1-Alpha - Identification of Residues Required for Binding to the Human Type-I Il-1 Receptor","volume":"6","author":"E Labriolatompkins","year":"1993","journal-title":"Protein Engineering"},{"key":"ref48","first-page":"Unit 10 11","article-title":"The Catalogue of Somatic Mutations in Cancer (COSMIC)","volume":"Chapter 10","author":"SA Forbes","year":"2008","journal-title":"Curr Protoc Hum Genet"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkq929","article-title":"COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer","volume":"39","author":"SA Forbes","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1530\/rep.1.01121","article-title":"Increased expression of interleukin-1 receptor type 1 in active endometriotic lesions","volume":"133","author":"C Lawson","year":"2007","journal-title":"Reproduction"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"D465","DOI":"10.1093\/nar\/gkq1091","article-title":"ModBase, a database of annotated comparative protein structure models, and associated resources","volume":"39","author":"U Pieper","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1021\/pr2009143","article-title":"Human proteome-scale structural modeling of E2\u2013E3 interactions exploiting interface motifs","volume":"11","author":"G Kar","year":"2011","journal-title":"Journal of proteome research"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1021\/ci300072q","article-title":"A strategy based on protein-protein interface motifs may help in identifying drug off-targets","volume":"52","author":"HB Engin","year":"2012","journal-title":"J Chem Inf Model"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1021\/pr400006k","article-title":"Exploiting conformational ensembles in modeling protein-protein interactions on the proteome scale","volume":"12","author":"G Kuzu","year":"2013","journal-title":"Journal of proteome research"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jmb.2008.04.071","article-title":"Architectures and functional coverage of protein-protein interfaces","volume":"381","author":"N Tuncbag","year":"2008","journal-title":"J Mol Biol"},{"key":"ref56","unstructured":"Hubbard SJ, Thornton JM (1993) \u2018NACCESS\u2019. Computer Program, Department of Biochemistry and Molecular Biology, University College, London."},{"key":"ref57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/prot.10628","article-title":"A method for simultaneous alignment of multiple protein structures","volume":"56","author":"M Shatsky","year":"2004","journal-title":"Proteins"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/prot.22668","article-title":"FiberDock: Flexible induced-fit backbone refinement in molecular docking","volume":"78","author":"E Mashiach","year":"2009","journal-title":"Proteins"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"W457","DOI":"10.1093\/nar\/gkq373","article-title":"FiberDock: a web server for flexible induced-fit backbone refinement in molecular docking","volume":"38","author":"E Mashiach","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/prot.21495","article-title":"FireDock: fast interaction refinement in molecular docking","volume":"69","author":"N Andrusier","year":"2007","journal-title":"Proteins"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"D829","DOI":"10.1093\/nar\/gkr929","article-title":"HotRegion: a database of predicted hot spot clusters","volume":"40","author":"E Cukuroglu","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1093\/bioinformatics\/btp242","article-title":"LS-SNP\/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures","volume":"25","author":"M Ryan","year":"2009","journal-title":"Bioinformatics"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1093\/bioinformatics\/btr254","article-title":"A graphical interface for the FoldX forcefield","volume":"27","author":"J Van Durme","year":"2011","journal-title":"Bioinformatics"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/prot.10104","article-title":"Increasing the precision of comparative models with YASARA NOVA\u2013a self-parameterizing force field","volume":"47","author":"E Krieger","year":"2002","journal-title":"Proteins"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T13:19:33Z","timestamp":1688995173000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003470"}},"subtitle":[],"editor":[{"given":"Yu","family":"Xia","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2014,2,13]]},"references-count":64,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,2,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003470","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,13]]}}}