E3 ubiquitin-protein ligase UBR2 (UBR2)

E3 ubiquitin-protein ligase UBR2 (UBR2) is an enzyme that mediates the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins, a key step in targeting proteins for degradation by the ubiquitin-proteasome system[1][5]. UBR2 is a RING-type E3 ligase that participates in the N-end rule pathway, which recognizes proteins with destabilizing N-terminal residues (N-degrons) and marks them for rapid proteasomal degradation[1][5]. Structurally, UBR2 contains a conserved UBR box domain responsible for recognizing target degrons[5]. UBR2 plays a crucial role in maintaining cellular protein quality control, regulating cell death, and is involved in biological processes such as spermatogenesis[4]. Overexpression of UBR2 has been observed in certain cancers, where it protects cells from caspase-independent cell death, thereby contributing to tumor cell survival and resistance to therapy[4]. There are currently no known drugs specifically targeting UBR2 in clinical use.

Other names

C6orf133KIAA0349N-recognin-2RING-type E3 ubiquitin transferase UBR2Ubiquitin-protein ligase E3-alpha-2Ubiquitin-protein ligase E3-alpha-IIbA49A4.1dJ392M17.3dJ242G1.1

Promotes ubiquitination of protein substrates with destabilizing N-terminal residues, targeting them for proteasomal degradation (N-end rule pathway)[1][5]. Regulates cell death pathways and contributes to resistance to caspase-independent cell death, especially in cancer contexts[4].