Target type: molecularfunction
An metal-dependent isopeptidase activity that cleaves ubiquitin from a target protein to which it is conjugated. [PMID:19489724]
Metal-dependent deubiquitinase activity is a crucial enzymatic process that plays a significant role in regulating protein degradation and various cellular signaling pathways. Deubiquitinases (DUBs) are a family of proteases that specifically remove ubiquitin (Ub) moieties from target proteins. This removal of ubiquitin chains, known as deubiquitination, is a dynamic and reversible process that counteracts the ubiquitination pathway, which typically leads to protein degradation by the proteasome.
Metal-dependent deubiquitinases, as their name suggests, rely on metal ions, usually zinc, for their catalytic activity. These metal ions are typically coordinated within the active site of the enzyme, where they facilitate the hydrolysis of the isopeptide bond between ubiquitin and its target protein. This hydrolysis reaction cleaves the ubiquitin chain, leading to the release of free ubiquitin and the deubiquitinated target protein.
The molecular function of metal-dependent deubiquitinase activity is multifaceted and crucial for maintaining cellular homeostasis:
1. **Protein Degradation Control:** Deubiquitination by metal-dependent DUBs can prevent the proteasomal degradation of target proteins, thereby regulating their abundance and function. This is essential for maintaining the stability of essential proteins and controlling cellular processes.
2. **Signaling Pathway Regulation:** Deubiquitination can modulate protein-protein interactions, influencing the activation or inactivation of signaling pathways. For example, by removing ubiquitin from signaling proteins, DUBs can activate or inhibit downstream signaling cascades.
3. **Cellular Processes Modulation:** Metal-dependent deubiquitinase activity is involved in a wide range of cellular processes, including DNA repair, transcription regulation, cell cycle control, and immune responses. These processes rely on precise regulation of protein stability and signaling, which is achieved through the dynamic interplay of ubiquitination and deubiquitination.
4. **Disease Pathogenesis:** Dysregulation of metal-dependent deubiquitinase activity can contribute to various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. Mutations or aberrant expression of DUBs can disrupt protein degradation, signaling pathways, and cellular homeostasis, leading to disease development.
In summary, metal-dependent deubiquitinase activity is a vital molecular process that governs protein stability, signaling pathways, and a wide range of cellular processes. By regulating ubiquitin levels and modifying protein fates, metal-dependent DUBs play a critical role in maintaining cellular homeostasis and ensuring proper cellular function. Their dysregulation is associated with various diseases, highlighting the importance of understanding and targeting these enzymes for therapeutic purposes.'
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Protein | Definition | Taxonomy |
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COP9 signalosome complex subunit 5 | A COP9 signalosome complex subunit 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92905] | Homo sapiens (human) |
26S proteasome non-ATPase regulatory subunit 7 | A 26S proteasome non-ATPase regulatory subunit 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P51665] | Homo sapiens (human) |
26S proteasome non-ATPase regulatory subunit 14 | A 26S proteasome non-ATPase regulatory subunit 14 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00487] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
oxyquinoline | Oxyquinoline: An antiseptic with mild fungistatic, bacteriostatic, anthelmintic, and amebicidal action. It is also used as a reagent and metal chelator, as a carrier for radio-indium for diagnostic purposes, and its halogenated derivatives are used in addition as topical anti-infective agents and oral antiamebics. quinolin-8-ol : A monohydroxyquinoline that is quinoline substituted by a hydroxy group at position 8. Its fungicidal properties are used for the control of grey mould on vines and tomatoes. | monohydroxyquinoline | antibacterial agent; antifungal agrochemical; antiseptic drug; iron chelator |
8-aminoquinoline | |||
8-methylquinoline | methylquinoline | ||
8-mercaptoquinoline | 8-mercaptoquinoline: structure given in first source | ||
bortezomib | amino acid amide; L-phenylalanine derivative; pyrazines | antineoplastic agent; antiprotozoal drug; protease inhibitor; proteasome inhibitor | |
carfilzomib | epoxide; morpholines; tetrapeptide | antineoplastic agent; proteasome inhibitor | |
belactosin a | belactosin A: isolated from Streptomyces; structure in first source |