Page last updated: 2024-10-24

ubiquitin ligase activator activity

Definition

Target type: molecularfunction

Binds to and increases the activity of a ubiquitin ligase. [GOC:dph, PMID:25619242]

Ubiquitin ligase activator activity is a molecular function that plays a critical role in the ubiquitin-proteasome system (UPS). The UPS is a cellular pathway responsible for protein degradation, a process crucial for maintaining cellular homeostasis and regulating various cellular processes. Ubiquitin ligase activator activity is specifically involved in the activation of ubiquitin ligases, enzymes that attach ubiquitin molecules to target proteins. This attachment, called ubiquitination, marks proteins for degradation by the proteasome.

Ubiquitin ligase activators, also known as E1 enzymes, act as the first step in the ubiquitination cascade. They activate ubiquitin by attaching it to a cysteine residue in their active site. This activation involves a two-step process:
1. The E1 enzyme first binds to ubiquitin, utilizing ATP hydrolysis for energy.
2. The activated ubiquitin is then transferred to the active site cysteine residue of the E1 enzyme, forming a thioester bond.

The activated ubiquitin molecule is then transferred to a second enzyme, called an E2 enzyme (ubiquitin-conjugating enzyme). E2 enzymes facilitate the transfer of ubiquitin to the target protein. Finally, E3 ubiquitin ligases (ubiquitin-protein ligases), which recognize specific protein substrates, bind to both the E2-ubiquitin complex and the target protein, facilitating the transfer of ubiquitin to the target protein.

Ubiquitin ligase activator activity is therefore essential for the proper functioning of the UPS. By activating ubiquitin ligases, E1 enzymes regulate the degradation of a vast array of proteins, including misfolded proteins, damaged proteins, and regulatory proteins. This regulation is crucial for maintaining cellular homeostasis, controlling cell cycle progression, signal transduction, and various other cellular processes.

Disruptions in ubiquitin ligase activator activity can lead to various diseases, including cancer, neurodegenerative diseases, and immunodeficiency disorders. For example, mutations in E1 enzymes have been linked to cancer development, while deficiencies in E1 activity can contribute to neurodegenerative diseases like Parkinson's disease.

Overall, ubiquitin ligase activator activity represents a critical molecular function in the UPS, playing a vital role in protein degradation and regulating diverse cellular processes.'
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Proteins (4)

ProteinDefinitionTaxonomy
Cell division cycle protein 20 homologA cell division cycle protein 20 homolog that is encoded in the genome of human. [PMID:11030144, PMID:20624902, PRO:KER]Homo sapiens (human)
RanBP-type and C3HC4-type zinc finger-containing protein 1A RanBP-type and C3HC4-type zinc finger-containing protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9BYM8]Homo sapiens (human)
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1A peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13526]Homo sapiens (human)
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENA phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN that is encoded in the genome of human. [PRO:PD, UniProtKB:P60484]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
juglonejuglone : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone in which the hydrogen at position 5 has been replaced by a hydroxy group. A plant-derived 1,4-naphthoquinone with confirmed antibacterial and antitumor activities.

juglone: structure
hydroxy-1,4-naphthoquinonegeroprotector;
herbicide;
reactive oxygen species generator
cycloheximidecycloheximide : A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus.

Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
antibiotic fungicide;
cyclic ketone;
dicarboximide;
piperidine antibiotic;
piperidones;
secondary alcohol
anticoronaviral agent;
bacterial metabolite;
ferroptosis inhibitor;
neuroprotective agent;
protein synthesis inhibitor
gliotoxingliotoxin : A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi.

Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.
dipeptide;
organic disulfide;
organic heterotetracyclic compound;
pyrazinoindole
antifungal agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor;
immunosuppressive agent;
mycotoxin;
proteasome inhibitor
1,4-naphthoquinone1,4-naphthoquinone : The parent structure of the family of 1,4-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 4 of the naphthalene ring. Derivatives have pharmacological properties.

naphthoquinone : A polycyclic aromatic ketone metabolite of naphthalene.
1,4-naphthoquinones
glycyrrhetinic acidcyclic terpene ketone;
hydroxy monocarboxylic acid;
pentacyclic triterpenoid
immunomodulator;
plant metabolite
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
propazolepropazole: RN given refers to parent cpd; structurebenzimidazoles
celastrolmonocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory drug;
antineoplastic agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
Hsp90 inhibitor;
metabolite
tretinoinall-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry.

retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).

Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
retinoic acid;
vitamin A
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
AP-1 antagonist;
human metabolite;
keratolytic drug;
retinoic acid receptor agonist;
retinoid X receptor agonist;
signalling molecule
apcinapcin: inhibits the anaphase-promoting complex; structure in first source
acetyl-11-ketoboswellic acidacetyl-11-ketoboswellic acid: a 5-lipoxygenase inhibitor; structure given in first sourcetriterpenoid