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Literature summary extracted from

  • Chen, S.; Yang, J.; Zhang, Y.; Duan, C.; Liu, Q.; Huang, Z.; Xu, Y.; Zhou, L.; Xu, G.
    Ubiquitin-conjugating enzyme UBE2O regulates cellular clock function by promoting the degradation of the transcription factor BMAL1 (2018), J. Biol. Chem., 293, 11296-11309 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.2.24 gene UBE2O, recombinant expression of Strep-tagged UBE2O in HEK-293 cells, coexpression with FLAG-tagged BMAL1 transcription factor Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.2.24 additional information UBE2O knockdown in U2-O2 cells. UBE2O knockdown elevates the amplitude of the circadian clock in human osteosarcoma U2OS cells. Full-length UBE2O and the CR2 truncation rescue the effect of UBE2O knockdown on the BMAL1 protein level Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.2.24 cytosol
-
 Homo sapiens 5829
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2.3.2.24 nucleus
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 Homo sapiens 5634
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Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [BMAL1]-L-lysine Homo sapiens mapping of the BMAL1-interacting domain in UBE2O [E1 ubiquitin-activating enzyme]-L-cysteine + [BMAL1]-N6-monoubiquitinyl-L-lysine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.24 Homo sapiens Q9C0C9
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-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.24 osteosarcoma cell
-
 Homo sapiens
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2.3.2.24 U2-OS cell
-
 Homo sapiens
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Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [BMAL1]-L-lysine mapping of the BMAL1-interacting domain in UBE2O Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [BMAL1]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [BMAL1]-L-lysine polyubiquitination of hydrocarbon receptor nuclear translocator-like protein 1 (Arntl or Bmal1). The critical Cys residue in the CR2 domain of UBE2O is responsible for BMAL1 ubiquitination Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [BMAL1]-N6-monoubiquitinyl-L-lysine
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 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.2.24 E2/E3 hybrid enzyme
-
 Homo sapiens
2.3.2.24 UBE2O
-
 Homo sapiens
2.3.2.24 ubiquitin-conjugating enzyme E2 O
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.2.24 malfunction UBE2O knockdown elevates the amplitude of the circadian clock in human osteosarcoma U2OS cells. Full-length UBE2O and the CR2 truncation rescue the effect of UBE2O knockdown on the BMAL1 protein level Homo sapiens
2.3.2.24 metabolism UBE2O is a critical regulator in the ubiquitin-proteasome system, which modulates BMAL1 transcriptional activity and circadian function by promoting BMAL1 ubiquitination and degradation under normal physiological conditions. UBE2O regulates BMAL1 protein level and stability Homo sapiens
2.3.2.24 physiological function dysregulation of the circadian rhythm is associated with many diseases, including diabetes, obesity, and cancer. Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Arntl or Bmal1) is the only clock gene whose loss disrupts circadian locomotor behavior in constant darkness. BMAL1 transcription factor levels are affected by proteasomal inhibition and by several enzymes in the ubiquitin-proteasome system. Specific interaction between BMAL1 and ubiquitin-conjugating enzyme E2 O (UBE2O), an E3-independent E2 ubiquitin-conjugating enzyme (i.e. hybrid E2/E3 enzyme) is detetcted, UBE2O expression reduces BMAL1 levels by promoting its ubiquitination and degradation. UBE2O expression/knockdown diminishes/increases, respectively, BMAL1-mediated transcriptional activity but does not affect BMAL1 gene expression. The conserved region 2 (CR2) in UBE2O significantly enhances BMAL1 ubiquitination and decreases BMAL1 protein levels. The CR2 domain alone can enhance BMAL1 ubiquitination and its protein level Homo sapiens