cysteine-type deubiquitinase activity

Definition

Target type: molecularfunction

An thiol-dependent isopeptidase activity that cleaves ubiquitin from a target protein to which it is conjugated. [GOC:jh2, PMID:30783221]

Cysteine-type deubiquitinases (DUBs) are a diverse family of proteases that specifically cleave ubiquitin from target proteins. They play crucial roles in regulating a wide range of cellular processes, including protein degradation, signal transduction, DNA repair, and immune response.

DUBs utilize a catalytic cysteine residue within their active site to perform the deubiquitination reaction. The mechanism involves the following steps:

1. **Substrate binding:** The DUB recognizes and binds to a ubiquitin chain attached to a target protein. This interaction is typically mediated by specific protein-protein interactions between the DUB and the ubiquitin chain.

2. **Nucleophilic attack:** The catalytic cysteine residue in the DUB's active site attacks the isopeptide bond linking the ubiquitin moiety to the target protein. This attack results in the formation of a covalent thioester intermediate between the ubiquitin and the DUB.

3. **Hydrolysis:** Water molecule attacks the thioester intermediate, leading to the release of free ubiquitin and the regeneration of the active DUB.

The deubiquitination activity of DUBs can have a profound impact on cellular signaling. By removing ubiquitin chains from target proteins, DUBs can:

- **Reverse the effects of ubiquitination:** Ubiquitination often serves as a signal for protein degradation or alters protein localization and activity. DUBs can counteract these effects, leading to the stabilization or reactivation of target proteins.

- **Modulate protein-protein interactions:** Ubiquitin chains can mediate protein-protein interactions, and DUBs can disrupt these interactions by removing the ubiquitin modifications.

- **Control signaling cascades:** DUBs can regulate the activity of signaling proteins by removing ubiquitin modifications that affect their stability, localization, or interactions with other proteins.

The dysregulation of DUB activity has been implicated in various human diseases, including cancer, neurodegenerative disorders, and immune disorders. Therefore, DUBs are emerging as promising targets for drug development.'
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Proteins (28)

Compounds (33)