USP5

Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter. Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains. Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein. Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1. Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels. Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3. Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4. Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination. May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity)..

Function from UniProtKB (P45974), read 2026-09-23. CC BY 4.0.