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Literature summary for 2.3.2.23 extracted from

  • Tan, J.M.E.; Cook, E.C.L.; van den Berg, M.; Scheij, S.; Zelcer, N.; Loregger, A.
    Differential use of E2 ubiquitin conjugating enzymes for regulated degradation of the rate-limiting enzymes HMGCR and SQLE in cholesterol biosynthesis (2019), Atherosclerosis, 281, 137-142 .
    View publication on PubMed

Protein Variants

Protein Variants Comment Organism
C94S site-directed mutagenesis, a catalytically inactive mutant Homo sapiens
additional information enzyme knockout by UBE2J2 siRNA in Hep-G2 cells. HEK293T cells lacking the E2 ubiquitin-conjugating enzymes UBE2J1, UBE2J2, and UBE2G2 are generated using a limited CRISPR/Cas9-based library. Hap1 cells lacking UBE2J2 are generated by CRISPR/Cas9-mediated genome editing Homo sapiens
additional information HEK293T cells lacking the E2 ubiquitin-conjugating enzymes UBE2J1, UBE2J2 and UBE2G2 are generated using a limited CRISPR/Cas9-based library Homo sapiens
additional information HEK293T cells lacking the E2 ubiquitin-conjugating enzymes UBE2J1, UBE2J2, and UBE2G2 are generated using a limited CRISPR/Cas9-based library Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine Homo sapiens
-
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P60604
-
-
Homo sapiens Q8N2K1
-
-
Homo sapiens Q9Y385
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HAP-1 cell
-
Homo sapiens
-
HEK-293T cell
-
Homo sapiens
-
Hep-G2 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
-
Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
-
?

Synonyms

Synonyms Comment Organism
UBE2G2
-
Homo sapiens
Ube2J1
-
Homo sapiens
UBE2J2
-
Homo sapiens

General Information

General Information Comment Organism
malfunction in UBE2G2 knockout cells, sterol-stimulated degradation of squalene monooxygenase (SQLE) is partly attenuated, but that of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is abolished Homo sapiens
malfunction in UBE2J1 knockout cells, sterol-stimulated degradation of squalene monooxygenase (SQLE) and of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) are unaffected Homo sapiens
malfunction in UBE2J2 knockout cells, sterol-stimulated degradation of squalene monooxygenase (SQLE), but not that of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is largely attenuated. RNAi-mediated silencing of UBE2J2 expression in HepG2 cells also attenuates sterol-stimulated degradation of SQLE in a proteasome-dependent manner Homo sapiens
physiological function MARCH6, an E3 ubiquitin ligase, specifically promotes cholesterol-stimulated ubiquitylation and subsequent proteasomal degradation of squalene monooxygenase (SQLE), but not of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). The sterol-dependent degradation machinery makes use of distinct E2 ubiquitin conjugating enzymes Homo sapiens
physiological function UBE2J2 is a new regulator of cellular cholesterol homeostasis in mammalian cells. MARCH6, an E3 ubiquitin ligase, specifically promotes cholesterol-stimulated ubiquitylation and subsequent proteasomal degradation of squalene monooxygenase (SQLE), but not of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). The sterol-dependent degradation machinery makes use of distinct E2 ubiquitin conjugating enzymes. The ability of UBE2J2 to support SQLE degradation critically depends on its enzymatic activity. UBE2J2 as an important partner of MARCH6 in cholesterol-stimulated degradation of SQLE, thereby contributing to the complex regulation of cellular cholesterol homeostasis Homo sapiens