Target type: molecularfunction
An isopeptidase activity that cleaves NEDD8 from a target protein to which it is conjugated. [GOC:mah, PMID:25628956]
DeNEDDylase activity refers to the enzymatic removal of the ubiquitin-like protein NEDD8 (Neural precursor cell expressed developmentally downregulated 8) from target proteins. This process, also known as deneddylation, plays a crucial role in regulating the activity of a diverse range of cellular processes. NEDD8 is conjugated to lysine residues on target proteins, a process termed NEDDylation. This modification can alter the activity, stability, or localization of the target protein. DeNEDDylation counteracts NEDDylation, effectively reversing the effects of NEDD8 conjugation.
DeNEDDylation is carried out by a family of enzymes known as NEDD8-specific proteases (DEN1, SENP1-SENP8, and COP9 signalosome). These enzymes recognize and bind to the NEDD8 moiety attached to the target protein. Through a complex enzymatic mechanism, they cleave the isopeptide bond between NEDD8 and the target protein, releasing NEDD8 and restoring the target protein to its unmodified state.
DeNEDDylation is essential for maintaining cellular homeostasis. It serves several key functions:
* **Regulation of protein activity:** DeNEDDylation can modulate the activity of target proteins by removing NEDD8, which can either activate or inhibit the protein's function. For example, deNEDDylation of the cullin-RING ligase (CRL) family of E3 ubiquitin ligases can activate their ubiquitin ligase activity, leading to the degradation of target proteins.
* **Control of protein stability:** NEDDylation can influence protein stability by regulating their susceptibility to proteasomal degradation. DeNEDDylation can prevent premature protein degradation, ensuring that proteins remain functional for the required duration.
* **Regulation of protein localization:** NEDDylation can affect protein localization by altering their interactions with cellular components. DeNEDDylation can reverse these changes, ensuring that proteins are directed to their correct cellular compartments.
In summary, deNEDDylase activity is a critical regulatory process that plays a vital role in cellular function. It controls the activity, stability, and localization of target proteins by removing NEDD8 from these proteins. This process is essential for maintaining cellular homeostasis and orchestrating a wide range of cellular processes.'
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Protein | Definition | Taxonomy |
---|---|---|
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) |
Ubiquitin carboxyl-terminal hydrolase isozyme L3 | A ubiquitin carboxyl-terminal hydrolase isozyme L3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P15374] | Homo sapiens (human) |
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) |
Ubiquitin carboxyl-terminal hydrolase isozyme L3 | A ubiquitin carboxyl-terminal hydrolase isozyme L3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P15374] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
vitamin k 3 | Vitamin K 3: A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo. | 1,4-naphthoquinones; vitamin K | angiogenesis inhibitor; antineoplastic agent; EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor; human urinary metabolite; nutraceutical |
8-mercaptoquinoline | 8-mercaptoquinoline: structure given in first source | ||
celastrol | monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory drug; antineoplastic agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Hsp90 inhibitor; metabolite | |
perifosine | ammonium betaine; phospholipid | EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor | |
4,5,6,7-tetrachloroindan-1,3-dione | 4,5,6,7-tetrachloroindan-1,3-dione: inhibits ubiquitin C-terminal hydrolase L1 | ||
9-deoxy-delta-9-prostaglandin d2 | 9-deoxy-delta-9-prostaglandin D2: has potent antineoplastic & weak smooth muscle contracting activities; structure given in first source prostaglandin J2 : A member of the class of prostaglandins J that consists of prosta-5,9,13-trien-1-oic acid substituted by an oxo group at position 11 and a hydroxy group at position 15 (the 5Z,13E,15S stereoisomer). | prostaglandins J | human metabolite |
acetyl isogambogic acid | acetyl isogambogic acid: structure in first source | ||
ldn 57444 | LDN 57444: inhibitor of ubiquitin C-terminal hydrolase-L1; structure in first source |