{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:36:46Z","timestamp":1772138206920,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":128,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board, India","doi-asserted-by":"crossref","award":["JBR\/2021\/000006"],"award-info":[{"award-number":["JBR\/2021\/000006"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Biotechnology, India","award":["BT\/PR40187\/BTIS\/137\/9\/2021"],"award-info":[{"award-number":["BT\/PR40187\/BTIS\/137\/9\/2021"]}]},{"name":"Institute of Bioinformatics and Applied Biotechnology, India","award":["IBAB\/MSCB\/182\/2022"],"award-info":[{"award-number":["IBAB\/MSCB\/182\/2022"]}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board, India","doi-asserted-by":"crossref","award":["JBR\/2021\/000006"],"award-info":[{"award-number":["JBR\/2021\/000006"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Biotechnology, India","award":["BT\/PR40187\/BTIS\/137\/9\/2021"],"award-info":[{"award-number":["BT\/PR40187\/BTIS\/137\/9\/2021"]}]},{"name":"Institute of Bioinformatics and Applied Biotechnology, India","award":["IBAB\/MSCB\/182\/2022"],"award-info":[{"award-number":["IBAB\/MSCB\/182\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite the vast amount of sequence data available, a significant disparity exists between the number of protein sequences identified and the relatively few structures that have been resolved. This disparity highlights the challenge in structural biology to bridge the gap between sequence information and 3D structural data, and the necessity for robust databases capable of linking distant homologs to known structures. Studies have indicated that there are a limited number of structural folds, despite the vast diversity of proteins. Hence, computational tools can enhance our ability to classify protein sequences, much before their structures are determined or their functions are characterized, thereby bridging the gap between sequence and structural data. GenDiS (Genomic Distribution of Superfamilies) is a repository with information on the genomic distribution of protein domain superfamilies, involving a one-time computational exercise to search for trusted homologs of protein domains of known structures against the vast sequence database. We have updated this database employing advanced bioinformatics tools, including DELTA-BLAST (domain enhanced lookup time accelerated BLAST) for initial detection of hits and HMMSCAN for validation, significantly improving the accuracy of domain identification. Using these tools, over 151 million sequence homologs for 2060 superfamilies [SCOPe (Structural Classification of Proteins extended)] were identified and 116 million out of them were validated as true positives. Through a case study on glycolysis-related enzymes, variations in domain architectures of these enzymes are explored, revealing evolutionary changes and functional diversity among these essential proteins. We present another case, LOG gene, where one can tune in and find significant mutations across the evolutionary lineage. The GenDiS database, GenDiS3, and the associated tools made available at https:\/\/caps.ncbs.res.in\/gendis3\/ offer a powerful resource for researchers in functional annotation and evolutionary studies.<\/jats:p>\n                  <jats:p>Database URL: https:\/\/caps.ncbs.res.in\/gendis3\/<\/jats:p>","DOI":"10.1093\/database\/baaf035","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T07:31:10Z","timestamp":1744270270000},"source":"Crossref","is-referenced-by-count":0,"title":["GenDiS3 database: census on the prevalence of protein domain superfamilies of known structure in the entire sequence database"],"prefix":"10.1093","volume":"2025","author":[{"given":"Sarthak","family":"Joshi","sequence":"first","affiliation":[{"name":"National Centre for Biological Sciences, Tata Institute of Fundamental Research , GKVK Campus, Bellary Road, Bangalore 560065,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailendu","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"Computational Biology, Insitute of Bioinformatics and Applied Biotechnology , Bangalore 560100,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhwani","family":"Kumar","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, Tata Institute of Fundamental Research , GKVK Campus, Bellary Road, Bangalore 560065,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adwait","family":"Joshi","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, Tata Institute of Fundamental Research , GKVK Campus, Bellary Road, Bangalore 560065,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meenakshi","family":"Iyer","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, Tata Institute of Fundamental Research , GKVK Campus, Bellary Road, Bangalore 560065,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-2367","authenticated-orcid":false,"given":"Ramanathan","family":"Sowdhamini","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, Tata Institute of Fundamental Research , GKVK Campus, Bellary Road, Bangalore 560065,","place":["India"]},{"name":"Computational Biology, Insitute of Bioinformatics and Applied Biotechnology , Bangalore 560100,","place":["India"]},{"name":"Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560012,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"2025092510514762200_R1","doi-asserted-by":"publisher","first-page":"D20","DOI":"10.1093\/nar\/gkab1112","article-title":"Database resources of the National Center for Biotechnology Information","volume":"50","author":"Sayers","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R2","doi-asserted-by":"publisher","first-page":"402","DOI":"10.2174\/138920209789177575","article-title":"Hidden Markov models and their applications in biological sequence analysis","volume":"10","author":"Yoon","year":"2009","journal-title":"Curr Genomics"},{"key":"2025092510514762200_R3","doi-asserted-by":"publisher","first-page":"3770","DOI":"10.1073\/pnas.0810767106","article-title":"Sequence context-specific profiles for homology searching","volume":"106","author":"Biegert","year":"2009","journal-title":"Proc Natl Acad Sci"},{"key":"2025092510514762200_R4","volume-title":"The Development of GenDiS V3.0: A Comprehensive Web Application for Organizing and Analyzing Protein Domain Superfamilies across Genomes","author":"Mohapatra","year":"2023"},{"key":"2025092510514762200_R5","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baz042","article-title":"GenDiS database update with improved approach and features to recognize homologous sequences of protein domain superfamilies","volume":"2019","author":"Iyer","year":"2019","journal-title":"Database"},{"key":"2025092510514762200_R6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002195","article-title":"Accelerated profile HMM searches","volume":"7","author":"Eddy","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"2025092510514762200_R7","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.mib.2005.10.014","article-title":"Unusual pathways and enzymes of central carbohydrate metabolism in Archaea","volume":"8","author":"Siebers","year":"2005","journal-title":"Curr Opin Microbiol"},{"key":"2025092510514762200_R8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-421","article-title":"BLAST+: architecture and applications","volume":"10","author":"Camacho","year":"2009","journal-title":"BMC Bioinf"},{"key":"2025092510514762200_R9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R10","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/357543a0","article-title":"One thousand families for the molecular biologist","volume":"357","author":"Chothia","year":"1992","journal-title":"Nature"},{"key":"2025092510514762200_R11","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/S0022-2836(05)80134-2","article-title":"SCOP: a structural classification of proteins database for the investigation of sequences and structures","volume":"247","author":"Murzin","year":"1995","journal-title":"J Mol Biol"},{"key":"2025092510514762200_R12","doi-asserted-by":"publisher","first-page":"D384","DOI":"10.1093\/nar\/gkac1096","article-title":"The conserved domain database in 2023","volume":"51","author":"Wang","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R13","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1677\/joe.1.05909","article-title":"Identification of \u03b1-enolase as a nuclear DNA-binding protein in the zona fasciculata but not the zona reticularis of the human adrenal cortex","volume":"184","author":"Wang","year":"2005","journal-title":"J Endocrinol"},{"key":"2025092510514762200_R14","doi-asserted-by":"publisher","first-page":"D252","DOI":"10.1093\/nar\/gki087","article-title":"GenDiS: genomic distribution of protein structural domain superfamilies","volume":"33","author":"Pugalenthi","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R15","doi-asserted-by":"publisher","first-page":"D553","DOI":"10.1093\/nar\/gkab1054","article-title":"SCOPe: improvements to the structural classification of proteins \u2013 extended database to facilitate variant interpretation and machine learning","volume":"50","author":"Chandonia","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R16","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/372631a0","article-title":"Protein superfamilles and domain superfolds","volume":"372","author":"Orengo","year":"1994","journal-title":"Nature"},{"key":"2025092510514762200_R17","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"Sievers","year":"2011","journal-title":"Mol Syst Biol"},{"key":"2025092510514762200_R18","doi-asserted-by":"publisher","first-page":"189D","DOI":"10.1093\/nar\/gkh034","article-title":"The ASTRAL compendium in 2004","volume":"32","author":"Chandonia","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R19","doi-asserted-by":"publisher","first-page":"D531","DOI":"10.1093\/nar\/gkr1096","article-title":"PASS2 version 4: an update to the database of structure-based sequence alignments of structural domain superfamilies","volume":"40","author":"Gandhimathi","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R20","doi-asserted-by":"publisher","first-page":"D418","DOI":"10.1093\/nar\/gkac993","article-title":"InterPro in 2022","volume":"51","author":"Paysan-Lafosse","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R21","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado1663","article-title":"Convergent evolution of plant prickles by repeated gene co-option over deep time","volume":"385","author":"Satterlee","year":"2024","journal-title":"Science"},{"key":"2025092510514762200_R22","doi-asserted-by":"publisher","first-page":"D266","DOI":"10.1093\/nar\/gkaa1079","article-title":"CATH: increased structural coverage of functional space","volume":"49","author":"Sillitoe","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R23","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R24","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J Mol Biol"},{"key":"2025092510514762200_R25","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.2-93.v2","article-title":"Improved performance of sequence search approaches in remote homology detection","volume":"2","author":"Joshi","year":"2014","journal-title":"F1000Research"},{"key":"2025092510514762200_R26","doi-asserted-by":"publisher","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: the protein families database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R27","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baac025","article-title":"PASS2.7: a database containing structure-based sequence alignments and associated features of protein domain superfamilies from SCOPe","volume":"2022","author":"Bhattacharyya","year":"2022","journal-title":"Database"},{"key":"2025092510514762200_R28","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-7-12","article-title":"Domain enhanced lookup time accelerated BLAST","volume":"7","author":"Boratyn","year":"2012","journal-title":"Biol Direct"},{"key":"2025092510514762200_R29","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2025092510514762200_R30","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baac025","article-title":"PASS2.7: a database containing structure-based sequence alignments and associated features of protein domain superfamilies from SCOPe","volume":"2022","author":"Bhattacharyya","year":"2022","journal-title":"Database"},{"key":"2025092510514762200_R31","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/S0969-2126(97)00260-8","article-title":"CATH \u2013 a hierarchic classification of protein domain structures","volume":"5","author":"Orengo","year":"1997","journal-title":"Structure"},{"key":"2025092510514762200_R32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/9781316761625","volume-title":"Prokaryotic Metabolism and Physiology","author":"Kim","year":"2019"},{"key":"2025092510514762200_R33","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1039\/C8MO00008E","article-title":"Genome-wide survey of remote homologues for protein domain superfamilies of known structure reveals unequal distribution across structural classes","volume":"14","author":"Iyer","year":"2018","journal-title":"Mol Omics"},{"key":"2025092510514762200_R34","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb25481j","article-title":"Tethering preferences of domain families co-occurring in multi-domain proteins","volume":"9","author":"Mohanty","year":"2013","journal-title":"Mol Biosyst"}],"container-title":["Database"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/database\/article-pdf\/doi\/10.1093\/database\/baaf035\/63136097\/baaf035.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/database\/article-pdf\/doi\/10.1093\/database\/baaf035\/63136097\/baaf035.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T14:51:54Z","timestamp":1758811914000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/database\/article\/doi\/10.1093\/database\/baaf035\/8127847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":34,"URL":"https:\/\/doi.org\/10.1093\/database\/baaf035","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.14.643262","asserted-by":"object"}]},"ISSN":["1758-0463"],"issn-type":[{"value":"1758-0463","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"baaf035"}}