{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gregorczyk M"],"funding":["Medical Research Council","Merck KGaA","Motor Neurone Disease Association","Canadian Institutes for Health Research"],"pagination":["e202201740"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10185812"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(7)"],"pubmed_abstract":["The NEK1 kinase controls ciliogenesis, mitosis, and DNA repair, and <i>NEK1</i> mutations cause human diseases including axial spondylometaphyseal dysplasia and amyotrophic lateral sclerosis. <i>C21ORF2</i> mutations cause a similar pattern of human diseases, suggesting close functional links with <i>NEK1</i> Here, we report that endogenous NEK1 and C21ORF2 form a tight complex in human cells. A C21ORF2 interaction domain \"CID\" 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-CID, and our model may explain why pathogenic mutations perturb the complex. We show that NEK1 mutations "],"journal":["Life science alliance"],"pubmed_title":["Functional characterization of C21ORF2 association with the NEK1 kinase mutated in human in diseases."],"pmcid":["PMC10185812"],"funding_grant_id":["Rouse/Apr20/877-791","PJT 180438","MC_UU_00018/5","MC_UU_12016/1"],"pubmed_authors":["Gregorczyk M","Pereira G","Hastie J","Lis P","Toth R","Brown F","Pastore G","Munoz I","Lange S","Streubel J","Munro M","Rouse J","Lamoliatte F","Carroll T","Macartney T","Durocher D"],"additional_accession":[]},"is_claimable":false,"name":"Functional characterization of C21ORF2 association with the NEK1 kinase mutated in human in diseases.","description":"The NEK1 kinase controls ciliogenesis, mitosis, and DNA repair, and <i>NEK1</i> mutations cause human diseases including axial spondylometaphyseal dysplasia and amyotrophic lateral sclerosis. <i>C21ORF2</i> mutations cause a similar pattern of human diseases, suggesting close functional links with <i>NEK1</i> Here, we report that endogenous NEK1 and C21ORF2 form a tight complex in human cells. A C21ORF2 interaction domain \"CID\" 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-CID, and our model may explain why pathogenic mutations perturb the complex. We show that NEK1 mutations ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jul","modification":"2026-07-15T01:42:32.4Z","creation":"2025-04-05T21:10:48.999Z"},"accession":"S-EPMC10185812","cross_references":{"pubmed":["37188479"],"doi":["10.26508/lsa.202201740"]}}