K11-linked deubiquitinase activity

Definition

Target type: molecularfunction

Hydrolysis of a ubiquitin unit from a ubiquitinated protein linked via the Lys11 residue of ubiquitin. [PMID:26412298]

K11-linked deubiquitinase activity is a specialized enzymatic function that specifically removes ubiquitin chains from proteins, targeting the K11 linkage type. Ubiquitination is a crucial post-translational modification that plays a critical role in diverse cellular processes, including protein degradation, signal transduction, DNA repair, and immune responses. K11-linked ubiquitin chains, characterized by the covalent linkage of ubiquitin molecules through their lysine 11 residue, often serve as regulatory signals, directing protein fate and function.

K11-linked deubiquitinases (K11 DUBs) are a subset of DUBs that possess the ability to selectively cleave these K11 chains, thus influencing the downstream cellular responses. Their precise molecular function involves the following steps:

1. **Substrate Recognition:** K11 DUBs recognize and bind to their specific substrates, often targeting proteins containing K11-linked ubiquitin chains. This recognition is achieved through complex interactions between the DUB and the substrate, involving both protein-protein and protein-ubiquitin interactions.
2. **Ubiquitin Chain Cleavage:** Once bound, the K11 DUB utilizes its catalytic domain to hydrolyze the isopeptide bond linking the K11 residue of one ubiquitin molecule to the lysine residue of another. This process effectively breaks the K11-linked ubiquitin chain, releasing free ubiquitin monomers and the deubiquitinated substrate.
3. **Regulation of Substrate Activity:** Deubiquitination by K11 DUBs can alter the activity of their substrates in various ways:
- **Degradation Inhibition:** By removing K11 ubiquitin chains, K11 DUBs can prevent the targeted protein from being degraded by the proteasome, thus preserving its function.
- **Signal Transduction Modulation:** K11-linked ubiquitin chains can act as signaling modules, and their removal by K11 DUBs can alter downstream signaling pathways.
- **Protein Trafficking Control:** K11 DUBs can regulate the localization and trafficking of proteins by influencing their ubiquitin-dependent interactions with other cellular components.

The precise biological consequences of K11 DUB activity depend on the specific enzyme involved and the nature of its substrates. These enzymes play critical roles in maintaining cellular homeostasis, regulating signaling pathways, and controlling protein turnover. Dysregulation of K11 DUB activity has been implicated in various human diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.'
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Proteins (1)

Compounds (1)