Ubiquitin-protein ligase E3 component n-recognin 1 (UBR1)

Ubiquitin-protein ligase E3 component n-recognin 1 (UBR1) is an E3 ubiquitin ligase that functions as a recognition component in the N-end rule pathway, a proteolytic system within the ubiquitin–proteasome system responsible for selective protein degradation[1][3][5]. UBR1 binds to substrate proteins bearing destabilizing N-terminal residues (N-degrons) and facilitates their polyubiquitination, targeting them for proteasomal degradation. This activity is crucial for protein quality control, including the clearance of unfolded or misfolded cytosolic proteins, and for regulating protein homeostasis[2][6]. UBR1 possesses RING-type and UBR-type zinc finger domains essential for its ligase activity[4]. Mutations in UBR1 are associated with Johanson–Blizzard syndrome, a rare genetic disorder characterized by multisystem involvement, especially exocrine pancreatic insufficiency, developmental delay, and growth abnormalities[1][3][6]. UBR1 also plays a role in metabolic regulation, such as negatively modulating the leucine-mTOR signaling pathway[3]. There are currently no approved drugs known to selectively target UBR1.

Other names

E3 ubiquitin-protein ligase UBR1N-recognin-1Ubiquitin-protein ligase E3-alpha-1Ubiquitin-protein ligase E3-alpha-IJBSE3a ligaseRING-type E3 ubiquitin transferase UBR1ubiquitin ligase E3 alpha-Iubiquitin-protein ligase E3-alpha

Substrate-specific ubiquitination via N-end rule pathway recognition. Catalyzes polyubiquitin chain formation on proteins with destabilizing N-terminal residues, targeting them for degradation.