{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T21:19:15Z","timestamp":1789334355228,"version":"build-2803163510"},"reference-count":65,"publisher":"Life Science Alliance, LLC","issue":"7","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12016\/1"],"award-info":[{"award-number":["MC_UU_12016\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"crossref","award":["PJT 180438"],"award-info":[{"award-number":["PJT 180438"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009945","name":"Merck KGaA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>\n                    The NEK1 kinase controls ciliogenesis, mitosis, and DNA repair, and\n                    <jats:italic>NEK1<\/jats:italic>\n                    mutations cause human diseases including axial spondylometaphyseal dysplasia and amyotrophic lateral sclerosis.\n                    <jats:italic>C21ORF2<\/jats:italic>\n                    mutations cause a similar pattern of human diseases, suggesting close functional links with\n                    <jats:italic>NEK1<\/jats:italic>\n                    . Here, we report that endogenous NEK1 and C21ORF2 form a tight complex in human cells. A C21ORF2 interaction domain \u201cCID\u201d at the C-terminus of NEK1 is necessary for its association with C21ORF2 in cells, and pathogenic mutations in this region disrupt the complex. AlphaFold modelling predicts an extended binding interface between a leucine-rich repeat domain in C21ORF2 and the NEK1\u2013CID, and our model may explain why pathogenic mutations perturb the complex. We show that NEK1 mutations that inhibit kinase activity or weaken its association with C21ORF2 severely compromise ciliogenesis, and that C21ORF2, like NEK1 is required for homologous recombination. These data enhance our understanding of how the NEK1 kinase is regulated, and they shed light on NEK1\u2013C21ORF2\u2013associated diseases.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202201740","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T15:55:17Z","timestamp":1684166117000},"page":"e202201740","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Functional characterization of C21ORF2 association with the NEK1 kinase mutated in human in diseases"],"prefix":"10.26508","volume":"6","author":[{"given":"Mateusz","family":"Gregorczyk","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5668-8452","authenticated-orcid":true,"given":"Graziana","family":"Pastore","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tannenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada"},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Genetics, University of Toronto","place":[", Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Carroll","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Streubel","sequence":"additional","affiliation":[{"name":"German Cancer Research Centre (DKFZ), Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany"},{"name":"DKFZ-ZMBH Alliance, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan","family":"Munro","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tannenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada"},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Genetics, University of Toronto","place":[", Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-7671","authenticated-orcid":true,"given":"Pawel","family":"Lis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6011-8647","authenticated-orcid":true,"given":"Sven","family":"Lange","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Lamoliatte","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-183X","authenticated-orcid":true,"given":"Thomas","family":"Macartney","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-0612","authenticated-orcid":true,"given":"Rachel","family":"Toth","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Brown","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7164-4098","authenticated-orcid":true,"given":"James","family":"Hastie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gislene","family":"Pereira","sequence":"additional","affiliation":[{"name":"German Cancer Research Centre (DKFZ), Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany"},{"name":"DKFZ-ZMBH Alliance, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-8635","authenticated-orcid":true,"given":"Daniel","family":"Durocher","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tannenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada"},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Genetics, University of Toronto","place":[", Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-8303","authenticated-orcid":true,"given":"John","family":"Rouse","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Protein Phosphorylation and Ubiquitylation Unit, Wellcome Trust Biocentre, University of Dundee","place":[", Dundee, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"2023082309435490000_6.7.e202201740.1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.75.3.983"},{"key":"2023082309435490000_6.7.e202201740.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-021920-092410"},{"key":"2023082309435490000_6.7.e202201740.3","doi-asserted-by":"publisher","DOI":"10.1097\/wco.0000000000001093"},{"key":"2023082309435490000_6.7.e202201740.4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww033"},{"key":"2023082309435490000_6.7.e202201740.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185780"},{"key":"2023082309435490000_6.7.e202201740.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.01.007"},{"key":"2023082309435490000_6.7.e202201740.7","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1648"},{"key":"2023082309435490000_6.7.e202201740.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.01.009"},{"key":"2023082309435490000_6.7.e202201740.9","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-5"},{"key":"2023082309435490000_6.7.e202201740.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2012.01.020"},{"key":"2023082309435490000_6.7.e202201740.11","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-014-0063-5"},{"key":"2023082309435490000_6.7.e202201740.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa3650"},{"key":"2023082309435490000_6.7.e202201740.13","doi-asserted-by":"publisher","DOI":"10.1038\/242009a0"},{"key":"2023082309435490000_6.7.e202201740.14","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.1162925"},{"key":"2023082309435490000_6.7.e202201740.15","doi-asserted-by":"publisher","DOI":"10.1101\/2022.04.01.486731"},{"key":"2023082309435490000_6.7.e202201740.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2019.05.006"},{"key":"2023082309435490000_6.7.e202201740.17","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0487-0"},{"key":"2023082309435490000_6.7.e202201740.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature02061"},{"key":"2023082309435490000_6.7.e202201740.19","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.4567"},{"key":"2023082309435490000_6.7.e202201740.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"2023082309435490000_6.7.e202201740.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3626"},{"key":"2023082309435490000_6.7.e202201740.22","first-page":"1","volume-title":"In Memoires de l'Academie Imperiale des Sciences de St-Petersbourg VII","volume":"11","author":"Kowalevsky","year":"1867"},{"key":"2023082309435490000_6.7.e202201740.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.12.5519"},{"key":"2023082309435490000_6.7.e202201740.24","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-07-0596"},{"key":"2023082309435490000_6.7.e202201740.25","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05435.x"},{"key":"2023082309435490000_6.7.e202201740.26","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12529"},{"key":"2023082309435490000_6.7.e202201740.27","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv362"},{"key":"2023082309435490000_6.7.e202201740.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.09.057"},{"key":"2023082309435490000_6.7.e202201740.29","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005080824"},{"key":"2023082309435490000_6.7.e202201740.30","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12550"},{"key":"2023082309435490000_6.7.e202201740.31","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38215"},{"key":"2023082309435490000_6.7.e202201740.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05325-w"},{"key":"2023082309435490000_6.7.e202201740.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01488-1"},{"key":"2023082309435490000_6.7.e202201740.34","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300016049"},{"key":"2023082309435490000_6.7.e202201740.35","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-129-1_16"},{"key":"2023082309435490000_6.7.e202201740.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.08.021"},{"key":"2023082309435490000_6.7.e202201740.37","doi-asserted-by":"publisher","DOI":"10.1186\/1747-1028-2-25"},{"key":"2023082309435490000_6.7.e202201740.38","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.96.4.1155"},{"key":"2023082309435490000_6.7.e202201740.39","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.7025261"},{"key":"2023082309435490000_6.7.e202201740.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1038"},{"key":"2023082309435490000_6.7.e202201740.41","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.20.2633"},{"key":"2023082309435490000_6.7.e202201740.42","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.833051"},{"key":"2023082309435490000_6.7.e202201740.43","doi-asserted-by":"publisher","DOI":"10.1101\/gad.331850.119"},{"key":"2023082309435490000_6.7.e202201740.44","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.040705.141236"},{"key":"2023082309435490000_6.7.e202201740.45","first-page":"821","article-title":"Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans","volume":"4","author":"Schultz","year":"1993","journal-title":"Cell Growth Differ"},{"key":"2023082309435490000_6.7.e202201740.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.03.036"},{"key":"2023082309435490000_6.7.e202201740.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.06.022"},{"key":"2023082309435490000_6.7.e202201740.48","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.3.2.207"},{"key":"2023082309435490000_6.7.e202201740.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.04.032"},{"key":"2023082309435490000_6.7.e202201740.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.12.004"},{"key":"2023082309435490000_6.7.e202201740.51","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(75)90269-7"},{"key":"2023082309435490000_6.7.e202201740.52","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00732"},{"key":"2023082309435490000_6.7.e202201740.53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.217"},{"key":"2023082309435490000_6.7.e202201740.54","doi-asserted-by":"publisher","DOI":"10.7554\/elife.44635"},{"key":"2023082309435490000_6.7.e202201740.55","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3622"},{"key":"2023082309435490000_6.7.e202201740.56","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V10122534"},{"key":"2023082309435490000_6.7.e202201740.57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150555"},{"key":"2023082309435490000_6.7.e202201740.58","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.157"},{"key":"2023082309435490000_6.7.e202201740.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101491"},{"key":"2023082309435490000_6.7.e202201740.60","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3201"},{"key":"2023082309435490000_6.7.e202201740.61","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00008"},{"key":"2023082309435490000_6.7.e202201740.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.12.027"},{"key":"2023082309435490000_6.7.e202201740.63","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.TM118.000372"},{"key":"2023082309435490000_6.7.e202201740.64","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-05037-6"},{"key":"2023082309435490000_6.7.e202201740.65","doi-asserted-by":"publisher","DOI":"10.1007\/bf02975837"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202201740","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:07:32Z","timestamp":1704877652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202201740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,15]]},"references-count":65,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,5,15]]},"published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.26508\/lsa.202201740"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202201740","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,15]]}}}