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. May be involved in pancreatic homeostasis. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (By similarity). 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 RECQL4. Present in skeletal muscle and liver (at protein level). Broadly expressed, with highest levels in skeletal muscle and heart. Expressed in acinar cells of the pancreas. In testes, expressed primarily in spermatogonia. Expressed in limb buds at 9.5-11.5 dpc. In models of cancer cachexia, induced in muscle during the progression of 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). Mice are viable and fertile, but show a decreased mass of skeletal muscle and adipose tissue. They have exocrine pancreatic insufficiency with impaired stimulus-secretion coupling and increased susceptibiliy to pancreatic injury. 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. Belongs to the UBR1 family. Contaminating sequence. Potential poly-A sequence.