E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation By similarity. Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Plays an essential role in extraembryonic development. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes.Michelle J. Henderson, J. Biol. Chem., Dec 2006; 281: 39990 - 40000. Lisa N. Kinch, Protein Sci., Feb 2005; 14: 360 - 367. Michelle J. Henderson, J. Biol. Chem., Jul 2002; 277: 26468 - 26478. Darren N. Saunders, Mol. Cell. Biol., Aug 2004; 24: 7225 - 7