Reactome: A Curated Pathway Database

ZNRF3 ubiquitinates FZD to promote its downregulation

Stable Identifier
R-HSA-4641253
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

ZNRF3 has been shown to ubiquitinate FZD4 in vivo, and inhibition of ZNRF3/RNF43 increases the protein levels of LRP6 and FZD8 at the cell surface (Hao et al, 2012; Jiang et al, 2013). Degradation of FZD and LRP is abrogated upon treatment of cells with bafilomycin A1 but not with MG132, suggesting that degradation of the receptors occurs in the lysosome. Consistent with this, mutational analysis suggests that FZD4 is multi-monoubiquitinated (Mukai et al, 2010).

Literature References
Participants
Participant Of
This entity is regulated by:
Title Physical Entity Activity
ubiquitin protein ligase activity of N4GlycoAsn-PalmS-WNT3A:FZD:LRP5/6:ZNRF3/RNF43 [plasma membrane] N4GlycoAsn-PalmS-WNT3A:FZD:LRP5/6:ZNRF3/RNF43 [plasma membrane] ubiquitin protein ligase activity (0061630)
Orthologous Events