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The specific interaction between E3 ubiquitin ligases and substrates (ESIs) precisely regulates Ub chain assembly, directing substrates toward different fates like degradation or signaling. In 2022, we released UbiBrowser 2.0, containing known\/predicted ESIs and deubiquitinase\u2013substrate interactions from 39 species. To address the urgent need for in-depth analysis of Ub chain functions, we updated UbiBrowser to v3.0 (http:\/\/ubibrowser.ncpsb.org.cn). This upgrade integrates a comprehensive framework linking ESIs, Ub chain types, and cellular effects. This includes 776 experimentally verified ESI\u2013Ub chain type associations, covering 8 Ub chain types and 15 cellular effects categories, more precisely characterizing human ESIs, and expanding the collection of known ESIs in UbiBrowser to 4300 unique pairs. Furthermore, building upon the original functionalities, the website introduces novel Ub chain-centric modules: (i) Ub Chain-Centric Interaction Explorer: integrates network graphs, tables, and evidence to display the relationships among ESIs, chain types, and cellular effects; (ii) Ub Chain-Centric Interaction Browser: provides bidirectional browsing of E3s\/substrates based on a Ub chain type classification tree. UbiBrowser 3.0 will facilitate a deeper understanding of the complex regulatory mechanisms of ubiquitination and support hypothesis generation on Ub chain type-dependent regulation of substrate fate and protein function.<\/jats:p>","DOI":"10.1093\/nar\/gkag962","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:17:21Z","timestamp":1790425041000},"source":"Crossref","is-referenced-by-count":0,"title":["UbiBrowser 3.0: towards comprehensively characterizing human ubiquitin ligase\u2013substrate interactions by incorporating ubiquitin chain information"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7142-3071","authenticated-orcid":false,"given":"Yingjie","family":"Qu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Academy of Military Medical Sciences , Beijing 102206 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