{"doi":"10.7554/elife.82951","title":"Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function","abstract":"Improving muscle function has great potential to improve the quality of life. To identify novel regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains, and integrated the data with previously acquired genomics and >300 molecular/phenotypic traits via quantitative trait loci mapping and correlation network analysis. These data identified thousands of associations between protein abundance and phenotypes and can be accessed online (https://muscle.coffeeprot.com/) to identify regulators of muscle function. We used this resource to prioritize targets for a functional genomic screen in human bioengineered skeletal muscle. This identified several negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation. We show UFMylation is up-regulated in a mouse model of amyotrophic lateral sclerosis, a disease that involves muscle atrophy. Furthermore, in vivo knockdown of UFMylation increased contraction force, implicating its role as a negative regulator of skeletal muscle function.","journal":"eLife","year":2022,"id":253929,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.919,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":900023,"name":"Ronnie Blazev","orcid":"0000-0002-2509-3907","position":1,"is_corresponding":false},{"id":900024,"name":"Richard J. Mills","orcid":"0000-0001-9735-2595","position":2,"is_corresponding":false},{"id":900025,"name":"Yaan‐Kit Ng","orcid":"0000-0002-8032-4931","position":3,"is_corresponding":false},{"id":900026,"name":"Kevin I. Watt","orcid":"0000-0001-7475-4487","position":4,"is_corresponding":false},{"id":900419,"name":"Daryn Chau","orcid":null,"position":5,"is_corresponding":false},{"id":763369,"name":"Paul Gregorevic","orcid":"0000-0002-7418-8945","position":6,"is_corresponding":false},{"id":900027,"name":"Peter J. Crouch","orcid":"0000-0002-7777-4747","position":7,"is_corresponding":false},{"id":900028,"name":"James B. Hilton","orcid":"0000-0002-2657-3566","position":8,"is_corresponding":false},{"id":457600,"name":"Leszek Lisowski","orcid":"0000-0002-4772-8651","position":9,"is_corresponding":false},{"id":897609,"name":"Peixiang Zhang","orcid":"0000-0003-1015-6431","position":10,"is_corresponding":false},{"id":242287,"name":"Karen Reue","orcid":"0000-0002-7487-2624","position":11,"is_corresponding":false},{"id":15457,"name":"Aldons J. Lusis","orcid":"0000-0001-9013-0228","position":12,"is_corresponding":false},{"id":35690,"name":"James E. Hudson","orcid":"0000-0003-0832-9356","position":13,"is_corresponding":false},{"id":688076,"name":"David E. James","orcid":"0000-0001-5946-5257","position":14,"is_corresponding":false},{"id":236691,"name":"Marcus Seldin","orcid":"0000-0001-8026-4759","position":15,"is_corresponding":false},{"id":308201,"name":"Benjamin L. Parker","orcid":"0000-0003-1818-2183","position":16,"is_corresponding":false},{"id":782400,"name":"Jeffrey Molendijk","orcid":"0000-0001-6575-504X","position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"36472367","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}