Search Results
Overview
| Uniprot ID | Q14258 |
|---|---|
| Protein Name | E3 ubiquitin/ISG15 ligase TRIM25 |
| Gene Name | TRIM25 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 237 | VRMTANRKVEQLQQE |
| 335 | ELNHKLIKGIHQSTI |
| 391 | SKEEKKSKKPPPVPA |
| 392 | KEEKKSKKPPPVPAL |
| 402 | PVPALPSKLPTFGAP |
| 425 | AGLEAAAKATSSHPN |
| 439 | NSTSLKAKVLETFLA |
| 573 | EKTLPSTKATRVGVL |
Function
Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase (PubMed:16352599). Involved in innate immune defense against viruses by mediating ubiquitination of RIGI and IFIH1 (PubMed:17392790, PubMed:29357390, PubMed:30193849, PubMed:31710640, PubMed:33849980, PubMed:36045682, PubMed:40719442). Mediates 'Lys-63'-linked polyubiquitination of the RIGI 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 (PubMed:17392790, PubMed:23950712). Mediates 'Lys-63'-linked polyubiquitination of IFIH1 (PubMed:30193849). Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway (PubMed:16352599, PubMed:17069755). Mediates estrogen action in various target organs (PubMed:22452784). Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (By similarity). Plays an essential role in the antiviral activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the replication of certain viruses. Mechanistically, mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1 that is required for its optimal binding to target mRNA (PubMed:28060952, PubMed:28202764). Also mediates the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (PubMed:36067236). Participates in autophagy suppression by ubiquitinating and degrading p62/SQSTM1 (PubMed:40542578)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0010494 | cytoplasmic stress granule |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005654 | nucleoplasm |
| Molecular Function | GO:0045296 | cadherin binding |
| Molecular Function | GO:0016874 | ligase activity |
| Molecular Function | GO:0039552 | RIG-I binding |
| Molecular Function | GO:0003723 | RNA binding |
| Molecular Function | GO:0003713 | transcription coactivator activity |
| Molecular Function | GO:0061630 | ubiquitin protein ligase activity |
| Molecular Function | GO:0004842 | ubiquitin-protein transferase activity |
| Molecular Function | GO:0008270 | zinc ion binding |
| Biological Process | GO:0140374 | antiviral innate immune response |
| Biological Process | GO:0002753 | cytoplasmic pattern recognition receptor signaling pathway |
| Biological Process | GO:0036503 | ERAD pathway |
| Biological Process | GO:0046597 | host-mediated suppression of symbiont invasion |
| Biological Process | GO:0045087 | innate immune response |
| Biological Process | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction |
| Biological Process | GO:0070936 | protein K48-linked ubiquitination |
| Biological Process | GO:0006513 | protein monoubiquitination |
| Biological Process | GO:0032880 | regulation of protein localization |
| Biological Process | GO:0046596 | regulation of viral entry into host cell |
| Biological Process | GO:0043627 | response to estrogen |
| Biological Process | GO:0006979 | response to oxidative stress |
| Biological Process | GO:0033280 | response to vitamin D |
| Biological Process | GO:0044790 | suppression of viral release by host |
| Biological Process | GO:0006511 | ubiquitin-dependent protein catabolic process |
| Biological Process | GO:0019076 | viral release from host cell |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.