Protein Variants | Comment | Organism |
---|---|---|
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 |
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 |
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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P60604 | - |
- |
Homo sapiens | P61077 | - |
- |
Homo sapiens | Q8N2K1 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
promonocytic leukemia cell line | - |
Homo sapiens | - |
U-937 cell | - |
Homo sapiens | - |
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 | Comment | Organism |
---|---|---|
UBE2D3 | - |
Homo sapiens |
UBE2G2 | - |
Homo sapiens |
UBE2J2 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | UBE2J2 depletion increases TRC8 expression levels in the presence of US2, and in this way, enhances US2-mediated HLA-I downregulation | Homo sapiens |
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 |
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 |
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 |
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 |
physiological function | the E2 ubiquitin-conjugating enzyme UBE2J2 is broadly involved in regulating the downregulation of immunoreceptors targeted by HCMV US2 | Homo sapiens |