E3 ubiquitin/ISG15 ligase TRIM25 (TRIM25)
The protein contains 630 amino acids for an estimated molecular weight of 70973 Da.
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 DDX58 and IFIH1 (PubMed:17392790, PubMed:30193849). 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 (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). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs7212260 | |
| dbSNP:rs205498 |
Biological Process
Cellular response to leukemia inhibitory factor
Defense response to virus
Innate immune response
Interferon-gamma-mediated signaling pathway
Negative regulation of type I interferon production
Negative regulation of viral entry into host cell
Negative regulation of viral release from host cell
Positive regulation of DNA-binding transcription factor activity
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of NF-kappaB transcription factor activity
Protein monoubiquitination
Regulation of protein localization
Regulation of viral entry into host cell
Regulation of viral release from host cell
Response to estrogen
Response to vitamin D
Translesion synthesis
Ubiquitin-dependent ERAD pathway
Ubiquitin-dependent protein catabolic process
Viral process
The reference OMIM entry for this protein is 600453
Tripartite motif-containing protein 25; trim25
Zinc finger protein 147; znf147
Estrogen-responsive finger protein; efp
CLONING
The human estrogen-responsive finger protein, a member of the RING finger protein family, was isolated by Inoue et al. (1993) from a human placenta cDNA library using an estrogen receptor-binding fragment containing an estrogen-responsive element. Since this estrogen-responsive finger protein is induced by estrogen via an estrogen-responsive element (ERE) in the 3-prime untranslated region of the gene, it is an attractive candidate for the correlation between estradiol levels and breast/ovarian cancer risk.MAPPING
By fluorescence in situ hybridization, Inoue et al. (1995) demonstrated that the human EFP gene, also called ZNF147, is located on 17q23.1 and that mouse Efp is located at 11C. Law et al. (1995) demonstrated that the ZNF147 gene is located within a YAC contig containing the myeloperoxidase (MPO; 606989) gene. Approximately 300 kb separate the 2 loci. This result was confirmed by fluorescence in situ hybridization, which again showed that the EFP gene is located at 17q23.1 and refined the assignment of the location of MPO to the same site. At the same time, they mapped the homologous gene in the mouse to chromosome 11 near the Mpo gene.GENE FUNCTION
Urano et al. (2002) demonstrated that EFP is a RING-finger-dependent ubiquitin ligase (E3) that targets proteolysis of 14-3-3-sigma (601290), a negative cell cycle regulator that causes G2 arrest. Urano et al. (2002) demonstrated that tumor growth of breast cancer MCF7 cells implanted in female athymic mice is reduced by treatment with antisense Efp oligonucleotide. Efp-overexpressing MCF7 cells in ovariectomized athymic mice generated tumors in the absence of estrogen. Loss of Efp function in mouse embryonic fibroblasts resulted in an accumulation of 14-3-3-sigma, which was responsible for reduced cell growth. Urano et al. (2002) concluded that their data provide an insight into the cell cycle machinery and tumorigenesis of breast cancer by identifying 14-3-3-sigma as a target for proteolysis by EFP, leading to cell proliferation. Gack et al. (2007) reported that the N-terminal caspase recruitment domains (CARDs) of RIGI (609631) undergo robust ubiquitination induced by TRIM25 in mammalian cells. The C-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIGI; this interaction effectively delivers the lys63-linked ubiquitin moiety to the N-terminal CARDs of RIGI, resulting in a marked increase in RIGI downstream signaling activity. The lys172 residue of RIGI is critical for efficient TRIM25-mediated ubiquitination and for MAVS (609676) binding, as well as the ability of RIGI to induce antiviral signal transduction. Gene targeting demonstrated that TRIM25 is essential not only for RIGI ubiquitination but also for RIGI-mediated interferon-beta (see 147640) production and antiviral activity in response to RNA virus infection. Thus, Gack et al. (2007) demonstrated that TRIM25 E3 ubiquitin ligase induces the lys63-linked ubiquitination of RIGI, which is crucial for the cytosolic RIGI signaling pathway to elicit host antiviral innate immunity. Dengue virus (see 614371) may become more virulent or show greater outbreak potential in a population exposed to new viral strains. Manokaran et al. (2015) identified a determinant of fitness in a new clade (PR-2B) of Dengue virus serotype-2 (DENV-2) that became dominant during a 1994 epidemic in Puerto Rico and replaced an endemic clade (PR-1) of DENV-2. PR-2B DENV-2 showed increased leve ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600453 was added.
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).