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UniProt functional annotation for Q61510 | ||
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| UniProt code: Q61510. |
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| Organism: | |
Mus musculus (Mouse). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus. |
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| Function: | |
Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of DDX58 and IFIH1 (By similarity). Mediates 'Lys-63'- linked polyubiquitination of the DDX58 N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection (By similarity). Mediates 'Lys-63'-linked polyubiquitination of IFIH1 (By similarity). Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs (By similarity). Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (By similarity). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (PubMed:29125140). {ECO:0000250|UniProtKB:Q14258, ECO:0000269|PubMed:29125140}. |
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| Catalytic activity: | |
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q14258}; |
| Catalytic activity: | |
Reaction=ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + [protein]-N-ISGyllysine.; EC=6.3.2.n3; Evidence={ECO:0000250|UniProtKB:Q14258}; |
| Pathway: | |
Protein modification; protein ubiquitination. |
| Subunit: | |
Interacts (via SPRY domain) with DDX58 (via CARD domain). Interacts with ZFHX3. Interacts with NLRP12; this interaction reduces the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked DDX58 activation. Interacts with the KHDC3/FILIA-OOEP/FLOPED scaffold complex and BLM at DNA replication forks (PubMed:29125140). {ECO:0000250|UniProtKB:Q14258, ECO:0000269|PubMed:29125140}. |
| Subcellular location: | |
Cytoplasm {ECO:0000250|UniProtKB:Q14258}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q14258}. Nucleus {ECO:0000269|PubMed:29125140}. Note=Localized to DNA replication forks. {ECO:0000269|PubMed:29125140}. |
| Tissue specificity: | |
Ubiquitous. {ECO:0000269|PubMed:7592654}. |
| Domain: | |
The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity. {ECO:0000250|UniProtKB:Q14258}. |
| Domain: | |
The C-terminal B30.2/SPRY domain interacts with the first N- terminal CARD domain of DDX58. {ECO:0000250|UniProtKB:Q14258}. |
| Ptm: | |
Auto-ISGylated. {ECO:0000250|UniProtKB:Q14258}. |
Annotations taken from UniProtKB at the EBI.