E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:14585983, PubMed:31268597, PubMed:30872531). 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 (PubMed:14585983, PubMed:31268597, PubMed:30872531). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (PubMed:14585983, PubMed:20080676). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (By similarity). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (PubMed:28708824). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (PubMed:28806172). Catalyzes ubiquitination and degradation of the N-terminal part of Nlrp1b following Nlrp1b activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:31268597, PubMed:30872531). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2 (PubMed:14585983, PubMed:20080676). Interacts with RECQL4 (By similarity). Interacts with Tex19.1 and Tex19.2; does not lead to Tex19.1 degradation and stabilizes it (PubMed:21103378). Interacts with L1RE1 (PubMed:28806172). Interacts with CASP8 (By similarity). Interacts with ATXN3 (By similarity). Interacts with UBE2O (PubMed:31268597). Associated with chromatin during meiosis. Highly expressed in skeletal muscle. Also expressed in heart, kidney and testis. Expressed in acinar cells of the pancreas. In testes, expressed primarily in spermatocytes. Expressed in cerebellum (PubMed:28806172). In models of cancer cachexia, induced specifically at the onset and during the progression of muscle wasting. The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif. The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides (By similarity). Male mice are viable but not fertile, due to massive apoptosis of spermatocytes. They have a reduction of testis weight of 68% and no detectable sperm in their epididymis. The seminiferous tubules contain reduced numbers of post-meiotic round, elongated spermatids and accumulation of pyknotic and zygotene-like nuclei. Female mice show severe prenatal lethality, but the rare surviving are fertile. Fibroblast cells display spontaneous chromosome instability and fragility (PubMed:14585983, PubMed:16488448, PubMed:28708824). UBR1 and UBR2 double knockout embryos die at midgestation, with defects in neurogenesis and cardiovascular development. These defects included reduced proliferation as well as precocious migration and differentiation of neural progenitor cells (PubMed:16606826). Belongs to the UBR1 family. Extended N-terminus. Truncated N-terminus. Intron retention.