E3 ubiquitin-protein ligase ZNRF1 (ZNRF1)

E3 ubiquitin-protein ligase ZNRF1 is an enzyme containing both a zinc finger and a RING finger motif, functioning as a RING-type E3 ubiquitin ligase highly expressed in the nervous system and other tissues[1][5][7]. ZNRF1 catalyzes the transfer of ubiquitin to substrate proteins, marking them for degradation by the proteasome or modulating their signaling functions. In neurons, it localizes primarily to synaptic vesicle membranes and participates in regulating neuronal transmission, synaptic plasticity, and neurite outgrowth[1][2]. ZNRF1 is implicated in processes such as neural development, axonal degeneration, and the neuroimmune response, partly by modulating signaling molecules like AKT1, EGFR, and caveolin-1[5]. It controls inflammation by regulating degradation of caveolin-1 and modulates Toll-like receptor 4 (TLR4)-mediated immune signaling; loss or dysfunction of ZNRF1 can suppress pro-inflammatory cytokine production and protect against sepsis in animal models[3][5]. ZNRF1 may also play a role in Schwann cell differentiation and is upregulated following nerve injury, suggesting a role in nerve regeneration and degeneration[1][5]. No clinical drugs officially target ZNRF1, but its activity affects pathways relevant to neurodegeneration, inflammation, and cellular homeostasis.

Other names

ZNRF1zinc and ring finger 1NIN283E3 ubiquitin-protein ligase ZNRF1nerve injury-induced gene 283 proteinRING-type E3 ubiquitin transferase ZNRF1zinc/RING finger protein 1nerve injury gene 283FLJ14846DKFZp434E229

Ubiquitination of substrate proteins leading to their proteasomal degradation or altered cellular signaling