Literature summary for 2.3.2.24 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 .

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Cloned(Commentary)

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

Protein Variants

Protein Variants	Comment	Organism
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

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
nucleus	-	Homo sapiens	5634	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
[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

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9C0C9	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
osteosarcoma cell	-	Homo sapiens	-
U2-OS cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
[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	-	?
[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	-	?

Synonyms

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

General Information

General Information	Comment	Organism
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
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
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

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Release 2023.1 (January 2023)