USP3

Domain

Both protease activity and an intact zinc finger are required for H2A monodeubiquitination.

Function

Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity. In response to DNA damage, deubiquitinates monoubiquitinated target proteins such as histone H2A and H2AX and thereby counteracts RNF168- and RNF8-mediated ubiquitination. In turn, participates in the recruitment of DNA damage repair factors to DNA break sites (PubMed:24196443). Required for proper progression through S phase and subsequent mitotic entry (PubMed:17980597). Acts as a positive regulator of TP53 by deubiquitinating and stabilizing it to promote normal cell proliferation and transformation (PubMed:28807825). Participates in establishing tolerance innate immune memory through non-transcriptional feedback. Mechanistically, negatively regulates TLR-induced NF-kappa-B signaling by targeting and removing the 'Lys-63'-linked polyubiquitin chains on MYD88 (PubMed:37971847). Negatively regulates the activation of type I interferon signaling by mediating 'Lys-63'-linked polyubiquitin chains on RIGI and IFIH1 (PubMed:24366338). Deubiquitinates also ASC/PYCARD, the central adapter mediating the assembly and activation of most inflammasomes, and thereby promotes inflammasome activation (PubMed:36050480).

Sequence Similarities

Belongs to the peptidase C19 family. USP3 subfamily.

Tissue Specificity

Expressed in all tissues examined, with strongest expression in pancreas.

Cellular localization

• Nucleus
• Cytoplasm
• Localizes preferentially with monoubiquitinated H2A to chromatin (PubMed:17980597). Upon NF-kappa-B signaling activation, exits the nucleus (PubMed:37971847).

Alternative names

Ubiquitin carboxyl-terminal hydrolase 3, Deubiquitinating enzyme 3, Ubiquitin thioesterase 3, Ubiquitin-specific-processing protease 3, USP3

Database links

swissprot:Q9Y6I4 entrezGene:9960 omim:604728 genbank:NM_006537