UBR5 (Ubiquitin protein ligase E3 component n-recognin 5; also HYD and EDD) is a 280-30kD member of the HECT E3 family of ubiquitin (Ub)protein ligases. It is ubiquitously expressed, and found in both the cytoplasm and nucleus of cells. In addition to ubiquination, UBR5 is functionally diverse. In the cytoplasm, it interacts with, and stabilizes APC, thereby increasing its concentration. In the nucleus (of smooth muscle cells), it stabilizes myocardin, a transcription factor that activates smooth muscle-specific genes. Perhaps its best known function involves DNA checkpoint activation. Following DNA damage, UBR5 promotes the phosphorylation of CHK2, which arrests the cell cycle at G2/M. Human UBR5 is 2799aa in length and contains a Ub-associated domain (aa180-215), two NLS’s (aa502-517 and 630-635), one UBR-type zinc finger region (aa1177-1244), a PABC region (aa2377-2454) and a HECT domain with a Ub-binding Cys residue (aa2462-2799). Over (aa1-227), human UBR5 shares 98% aa identity with mouse UBR5.