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Herein, we identified UBC13 (UBE2N) as an E2 ubiquitin\u2010conjugating enzyme for RNF213 E3 ubiquitin ligase by yeast two\u2010hybrid screening with a fragment containing RNF213 RING domain as bait, and the immunocomplex of RNF213\u2010UBC13 was detected <jats:italic>in vivo<\/jats:italic>. Analysis of the ubiquitin chain on RNF213 by monitoring autoubiquitination showed that RNF213 was autoubiquitinated in a K63 chain fashion, but not in a K48 chain fashion. Finally, this RNF213 ubiquitination in a UBC13\u2010dependent manner was required for cell mobility and invasion activity for HUVEC cells in UBC13 knock\u2010down and ubiquitination\u2010dead RNF213 mutant expressing experiments. These findings demonstrated that RNF213 is a K63\u2010linked E3 ubiquitin ligase, and UBC13 is responsible for RNF213 dependent ubiquitination. The RNF213\u2010UBC13 axis may be associated with angiogenic activity and MMD.<\/jats:p>","DOI":"10.1096\/fba.2019-00092","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T09:45:10Z","timestamp":1611135910000},"page":"243-258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["UBC13 is an RNF213\u2010associated E2 ubiquitin\u2010conjugating enzyme, and Lysine 63\u2010linked ubiquitination by the RNF213\u2010UBC13 axis is responsible for angiogenic activity"],"prefix":"10.1096","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-3938","authenticated-orcid":false,"given":"Toshiyuki","family":"Habu","sequence":"first","affiliation":[{"name":"Department of Food Sciences and Nutrition School of Food Sciences and Nutrition Mukogawa Women\u2019s University Nishinomiya Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji 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