Functions as an ubiquitin ligase protein, and regulates Notch signaling (PubMed:35782979, PubMed:40127622). By promoting the ubiquitination and subsequent degradation of target proteins, it can block activation of the Notch signaling pathway, potentially acting as a tumor suppressor in human cancers (PubMed:31854042, PubMed:35782979, PubMed:40127622). {ECO:0000269|PubMed:31854042, ECO:0000269|PubMed:35782979, ECO:0000269|PubMed:40127622}. [Isoform 3]: Involved in the angiogenic EPHB4 kinase degradation in cancer cell. . This is the function of DTX3 (deltex E3 ubiquitin ligase 3, Ensembl gene identifier ENSG00000178498).