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The GPCR database, GPCRdb serves &amp;gt;4\u00a0000 researchers every month and offers reference data, analysis of own or literature data, experiment design and dissemination of published datasets. Here, we describe new and updated GPCRdb resources with a particular focus on integration of sequence, structure and function. GPCRdb contains all human non-olfactory GPCRs (and &amp;gt;27\u00a0000 orthologs), G-proteins and arrestins. It includes over 2\u00a0000 drug and in-trial agents and nearly 200\u00a0000 ligands with activity and availability data. GPCRdb annotates all published GPCR structures (updated monthly), which are also offered in a refined version (with re-modeled missing\/distorted regions and reverted mutations) and provides structure models of all human non-olfactory receptors in inactive, intermediate and active states. Mutagenesis data in the GPCRdb spans natural genetic variants, GPCR-G protein interfaces, ligand sites and thermostabilising mutations. A new sequence signature tool for identification of functional residue determinants has been added and two data driven tools to design ligand site mutations and constructs for structure determination have been updated extending their coverage of receptors and modifications. The GPCRdb is available at https:\/\/gpcrdb.org.<\/jats:p>","DOI":"10.1093\/nar\/gkaa1080","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T03:27:05Z","timestamp":1603423625000},"page":"D335-D343","source":"Crossref","is-referenced-by-count":343,"title":["GPCRdb in 2021: integrating GPCR sequence, structure and function"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5514-6021","authenticated-orcid":false,"given":"Albert J","family":"Kooistra","sequence":"first","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"}]},{"given":"Stefan","family":"Mordalski","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"}]},{"given":"G\u00e1sp\u00e1r","family":"P\u00e1ndy-Szekeres","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"},{"name":"Medicinal Chemistry Research Group, Research Center for Natural Sciences, Budapest H-1117, Hungary"}]},{"given":"Mauricio","family":"Esguerra","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"}]},{"given":"Alibek","family":"Mamyrbekov","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"}]},{"given":"Christian","family":"Munk","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"}]},{"given":"Gy\u00f6rgy M","family":"Keser\u0171","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Research Group, Research Center for Natural Sciences, Budapest H-1117, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-7561","authenticated-orcid":false,"given":"David\u00a0E","family":"Gloriam","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark"}]}],"member":"286","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"2021010313131852900_B1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/1471-2164-8-338","article-title":"The G protein-coupled receptor subset of the rat genome","volume":"8","author":"Gloriam","year":"2007","journal-title":"BMC Genomics"},{"key":"2021010313131852900_B2","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"UniProt: a worldwide hub of protein knowledge","volume":"47","author":"UniProt, C.","year":"2019","journal-title":"Nucleic. 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