{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["van Gerwen J"],"funding":["Wellcome Trust","NIGMS NIH HHS","Biotechnology and Biological Sciences Research Council"],"pubmed_abstract":["Protein ubiquitination regulates cell biology through diverse avenues, from quality control-linked protein degradation to signaling functions such as modulating protein-protein interactions and enzyme activation. Mass spectrometry-based proteomics has allowed proteome-scale quantification of hundreds of thousands of ubiquitination sites (ubi-sites), however the functional importance and regulatory roles of most ubi-sites remain undefined. Here, we assembled a human reference ubiquitinome of 108,341 ubi-sites by harmonizing public proteomics data. We identified a core subset of ubi-sites under evolutionary constraint through alignment of ubiquitin proteomics data from six non-human species, and determined ultra-conserved ubi-sites recurring at regulatory hotspots within protein domains. Per"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.10.08.681129"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12632403"],"repository":["biostudies-literature"],"pubmed_title":["The functional landscape of the human ubiquitinome."],"pmcid":["PMC12632403"],"funding_grant_id":["223745/Z/21/Z","R35 GM148339","BB/Y513829/1","DP2 GM119132","R01 GM136994","BB/S017054/1"],"pubmed_authors":["Studer R","Lang K","Fottner M","Carrano AC","Troemel ER","van Gerwen J","Beltrao P","Bakowski MA","Bennett EJ","Harper JW","Strumillo M","Wang S","Martin MJ","Jones AR","Barrio-Hernandez I","Schnacke P","Busby B","Vizcaino JA","Boswell E"],"additional_accession":[]},"is_claimable":false,"name":"The functional landscape of the human ubiquitinome.","description":"Protein ubiquitination regulates cell biology through diverse avenues, from quality control-linked protein degradation to signaling functions such as modulating protein-protein interactions and enzyme activation. Mass spectrometry-based proteomics has allowed proteome-scale quantification of hundreds of thousands of ubiquitination sites (ubi-sites), however the functional importance and regulatory roles of most ubi-sites remain undefined. Here, we assembled a human reference ubiquitinome of 108,341 ubi-sites by harmonizing public proteomics data. We identified a core subset of ubi-sites under evolutionary constraint through alignment of ubiquitin proteomics data from six non-human species, and determined ultra-conserved ubi-sites recurring at regulatory hotspots within protein domains. Per","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-07-02T03:14:15.756Z","creation":"2026-07-02T03:08:54.852Z"},"accession":"S-EPMC12632403","cross_references":{"pubmed":["41279051"],"doi":["10.1101/2025.10.08.681129"]}}