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Literature summary extracted from

  • van de Weijer, M.L.; Schuren, A.B.C.; van den Boomen, D.J.H.; Mulder, A.; Claas, F.H.J.; Lehner, P.J.; Lebbink, R.J.; Wiertz, E.J.H.J.
    Multiple E2 ubiquitin-conjugating enzymes regulate human cytomegalovirus US2-mediated immunoreceptor downregulation (2017), J. Cell Sci., 130, 2883-2892 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
2.3.2.23 additional information lentiviral CRISPR/Cas9 library targeting of all known human E2 enzymes is used to assess their involvement in US2-mediated HLA-I downregulation. CRISPR gRNAs targeting UBE2D3 induce rescue of eGFP-HLA-A2 expression in US2-expressing cell. The anti-UBE2D3 gRNAs also increase the levels of endogenous HLA-A3 in these US2-expressing cells Homo sapiens
2.3.2.23 additional information lentiviral CRISPR/Cas9 library targeting of all known human E2 enzymes is used to assess their involvement in US2-mediated HLA-I downregulation. Generation of a UBE2G2-null cell line. CRISPR gRNAs targeting UBE2G2 induce rescue of eGFP-HLA-A2 expression in US2-expressing cell. Expression of gRNAs targeting UBE2G2 induce the strongest rescue of eGFP-HLA-A2. The anti-UBE2G2 gRNAs also increase the levels of endogenous HLA-A3 in these US2-expressing cells. By contrast, targeting the UBE2G2 homologue UBE2G1 with CRISPR gRNAs does not affect eGFP-HLA-A2 expressions. Removal of UBE2G2 in causes a growth defect, but is not lethal. HLA-I levels are increased in UBE2G2-null cells compared to control cells, and US2 protein levels are increased, likely due to the stabilization of the US2 ERAD complex in the absence of UBE2G2 Homo sapiens
2.3.2.23 additional information lentiviral CRISPR/Cas9 library targeting of all known human E2 enzymes is used to assess their involvement in US2-mediated HLA-I downregulation. Generation of a UBE2J2-null cell line. The strong increase inHLA-I degradation upon UBE2J2 knockout is not caused by increased US2 levels. UBE2J2 depletion increases TRC8 expression levels in the presence of US2, and in this way, enhances US2-mediated HLA-I downregulation Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.23 Homo sapiens P60604
-
-
2.3.2.23 Homo sapiens P61077
-
-
2.3.2.23 Homo sapiens Q8N2K1
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.23 promonocytic leukemia cell line
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Homo sapiens
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2.3.2.23 U-937 cell
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Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.23 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

EC Number Synonyms Comment Organism
2.3.2.23 UBE2D3
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Homo sapiens
2.3.2.23 UBE2G2
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Homo sapiens
2.3.2.23 UBE2J2
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Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.2.23 malfunction UBE2J2 depletion increases TRC8 expression levels in the presence of US2, and in this way, enhances US2-mediated HLA-I downregulation Homo sapiens
2.3.2.23 metabolism misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol and degraded by the ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), the viral US2 protein targets HLA class I molecules (HLA-I) for degradation via ERAD to avoid elimination by the immune system. US2-mediated degradation of HLA-I serves as a paradigm of ERAD and has facilitated the identification of TRC8 (also known as RNF139) as an E3 ubiquitin ligase. Identification of multiple E2 enzymes that are involved in the US2-mediated HLA-I downregulation process, of which UBE2G2 is crucial for the degradation of various immunoreceptors. UBE2G2 affects US2-mediated degradation of HLA-I Homo sapiens
2.3.2.23 metabolism misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol and degraded by the ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), the viral US2 protein targets HLA class I molecules (HLA-I) for degradation via ERAD to avoid elimination by the immune system. US2-mediated degradation of HLA-I serves as a paradigm of ERAD and has facilitated the identification of TRC8 (also known as RNF139) as an E3 ubiquitin ligase. Identification of multiple E2 enzymes that are involved in the US2-mediated HLA-I downregulation process. UBE2D3 affects US2-mediated degradation of HLA-I Homo sapiens
2.3.2.23 metabolism misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol and degraded by the ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), the viral US2 protein targets HLA class I molecules (HLA-I) for degradation via ERAD to avoid elimination by the immune system. US2-mediated degradation of HLA-I serves as a paradigm of ERAD and has facilitated the identification of TRC8 (also known as RNF139) as an E3 ubiquitin ligase. Identification of multiple E2 enzymes that are involved in the US2-mediated HLA-I downregulation process. UBE2J2 counteracts US2-mediated HLA-I downregulation, UBE2J2 counteracts US2-induced ERAD by downregulating TRC8 expression Homo sapiens
2.3.2.23 physiological function the E2 ubiquitin-conjugating enzyme UBE2G2 is broadly involved in regulating the downregulation of immunoreceptors targeted by HCMV US2. The E2 ubiquitin conjugating enzyme UBE2G2 to be essential for US2-mediated HLA-I downregulation Homo sapiens
2.3.2.23 physiological function the E2 ubiquitin-conjugating enzyme UBE2J2 is broadly involved in regulating the downregulation of immunoreceptors targeted by HCMV US2 Homo sapiens