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Available structures
PDB Ortholog search: PDBe RCSB
Aliases TRIM25, EFP, RNF147, Z147, ZNF147, tripartite motif containing 25
External IDs MGI: 102749 HomoloGene: 48325 GeneCards: TRIM25
EC number
RNA expression pattern
PBB GE TRIM25 206911 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 17: 56.89 – 56.91 Mb Chr 11: 89 – 89.02 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.[3][4]


The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primarily function as ubiquitin ligases that regulate the innate response to infection.[5] TRIM25 localizes to the cytoplasm. The presence of potential DNA-binding and dimerization-transactivation domains suggests that this protein may act as a transcription factor, similar to several other members of the TRIM family. Expression of the gene is upregulated in response to estrogen, and it is thought to mediate estrogen actions in breast cancer as a primary response gene.[4]

Domain Architecture[edit]

TRIM25 has an N-terminal RING domain, followed by a B-box type 1 domain, a B-box type 2 domain, a coiled-coil domain (CCD) and a C-terminal SPRY domain. The RING domain coordinates two zinc atoms and is essential for recruiting ubiquitin-conjugating enzymes. The function of the B-box domains is unknown. The CCD domain has been implicated in multimerization and other protein-protein interactions.[6] The SPRY domain is required for substrate recruitment.[7] The NMR chemical shifts for backbone of the PRYSPRY domain of TRIM25 is assigned based on triple-resonance experiments using uniformly isotopic labeled protein and the secondary structure of the domain PRYSPRY domain of TRIM25 predicted based on the NMR assignments.[8]

TRIM25 functions[edit]

TRIM25 plays a key role in the RIG-I signaling pathway. RIG-I is a cytosolic pattern recognition receptor that senses viral RNA. Following RNA recognition, the caspase recruitment domain (CARD) of RIG-I undergoes K(63)-linked ubiquitination by TRIM25. The RING and SPRY domains of TRIM25 mediate its interaction with RIG-I. IFN production then follows by an intracellular signaling pathway involving IRF3.[9]

Viral escape[edit]

To avoid IFN production, the non structural protein (NS1) of influenza will interact with CCD domain of TRIM25 to block RIG-I ubiquitination. Some studies have shown that a deletion of the CCD domain of TRIM25 prevents the binding of NS1.[10] Without this ubiquitination, there won’t be IFN production.


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Inoue S, Orimo A, Matsuda Y, Inazawa J, Emi M, Nakamura Y, Hori T, Muramatsu M (Jan 1995). "Chromosome mapping of human (ZNF147) and mouse genes for estrogen-responsive finger protein (efp), a member of the RING finger family". Genomics. 25 (2): 581–3. doi:10.1016/0888-7543(95)80064-S. PMID 7789997. 
  4. ^ a b "Entrez Gene: TRIM25 tripartite motif-containing 25". 
  5. ^ D'Cruz AA, Kershaw NJ, Chiang JJ, Wang MK, Nicola NA, Babon JJ, Gack MU, Nicholson SE (2013). "Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of antiviral signalling". The Biochemical Journal. 456 (2): 231–40. doi:10.1042/BJ20121425. PMC 4012390Freely accessible. PMID 24015671. 
  6. ^ Haik KG (Jul 1985). "Visual difficulties from video display terminals". Southern Medical Journal. 78 (7): 887–8. doi:10.1097/00007611-198507000-00031. 
  7. ^ Pilka L, Trávník P, Dvorák M, Tesarík J, Ventruba P, Krejcí K, Soska J (Aug 1985). "[Delivery after intrauterine embryo transfer obtained by fertilization and oocyte culture in vitro]". Ceskoslovenská Gynekologie. 50 (7): 452–9. PMID 4042170. 
  8. ^ Kong, Chen; Penumutchu, Srinivasa R.; Hung, Kuo-wei; Huang, Huiying; Lin, Tianwei; Yu, Chin (2015-02-22). "Backbone resonance assignments of the PRYSPRY domain of TRIM25". Biomolecular NMR Assignments. 9 (2): 313–315. doi:10.1007/s12104-015-9599-x. ISSN 1874-2718. 
  9. ^ Gack MU, Kirchhofer A, Shin YC, Inn KS, Liang C, Cui S, Myong S, Ha T, Hopfner KP, Jung JU (Oct 2008). "Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction". Proceedings of the National Academy of Sciences of the United States of America. 105 (43): 16743–8. doi:10.1073/pnas.0804947105. PMC 2575490Freely accessible. PMID 18948594. 
  10. ^ Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, García-Sastre A (May 2009). "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I". Cell Host & Microbe. 5 (5): 439–49. doi:10.1016/j.chom.2009.04.006. PMC 2737813Freely accessible. PMID 19454348. 

Further reading[edit]

  • Horie K, Urano T, Ikeda K, Inoue S (Jun 2003). "Estrogen-responsive RING finger protein controls breast cancer growth". The Journal of Steroid Biochemistry and Molecular Biology. 85 (2-5): 101–4. doi:10.1016/S0960-0760(03)00209-7. PMID 12943693. 
  • Inoue S, Orimo A, Hosoi T, Kondo S, Toyoshima H, Kondo T, Ikegami A, Ouchi Y, Orimo H, Muramatsu M (Dec 1993). "Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein". Proceedings of the National Academy of Sciences of the United States of America. 90 (23): 11117–21. doi:10.1073/pnas.90.23.11117. PMC 47933Freely accessible. PMID 8248217. 
  • Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
  • Ikeda K, Inoue S, Orimo A, Sano M, Watanabe T, Tsutsumi K, Muramatsu M (Jul 1997). "Multiple regulatory elements and binding proteins of the 5'-flanking region of the human estrogen-responsive finger protein (efp) gene". Biochemical and Biophysical Research Communications. 236 (3): 765–71. doi:10.1006/bbrc.1997.7046. PMID 9245730. 
  • Ikeda K, Orimo A, Higashi Y, Muramatsu M, Inoue S (Apr 2000). "Efp as a primary estrogen-responsive gene in human breast cancer". FEBS Letters. 472 (1): 9–13. doi:10.1016/S0014-5793(00)01421-6. PMID 10781795. 
  • Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–51. doi:10.1093/emboj/20.9.2140. PMC 125245Freely accessible. PMID 11331580. 
  • Urano T, Saito T, Tsukui T, Fujita M, Hosoi T, Muramatsu M, Ouchi Y, Inoue S (Jun 2002). "Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth". Nature. 417 (6891): 871–5. doi:10.1038/nature00826. PMID 12075357. 
  • Shimada N, Suzuki T, Inoue S, Kato K, Imatani A, Sekine H, Ohara S, Shimosegawa T, Sasano H (Apr 2004). "Systemic distribution of estrogen-responsive finger protein (Efp) in human tissues". Molecular and Cellular Endocrinology. 218 (1-2): 147–53. doi:10.1016/j.mce.2003.12.008. PMID 15130519. 
  • Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (Jan 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455. 
  • Suzuki T, Urano T, Tsukui T, Horie-Inoue K, Moriya T, Ishida T, Muramatsu M, Ouchi Y, Sasano H, Inoue S (Sep 2005). "Estrogen-responsive finger protein as a new potential biomarker for breast cancer". Clinical Cancer Research. 11 (17): 6148–54. doi:10.1158/1078-0432.CCR-05-0040. PMID 16144914. 
  • Nakayama H, Sano T, Motegi A, Oyama T, Nakajima T (Nov 2005). "Increasing 14-3-3 sigma expression with declining estrogen receptor alpha and estrogen-responsive finger protein expression defines malignant progression of endometrial carcinoma". Pathology International. 55 (11): 707–15. doi:10.1111/j.1440-1827.2005.01900.x. PMID 16271083. 
  • Nakasato N, Ikeda K, Urano T, Horie-Inoue K, Takeda S, Inoue S (Dec 2006). "A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated with ISG15". Biochemical and Biophysical Research Communications. 351 (2): 540–6. doi:10.1016/j.bbrc.2006.10.061. PMID 17069755. 
  • Nakajima A, Maruyama S, Bohgaki M, Miyajima N, Tsukiyama T, Sakuragi N, Hatakeyama S (May 2007). "Ligand-dependent transcription of estrogen receptor alpha is mediated by the ubiquitin ligase EFP". Biochemical and Biophysical Research Communications. 357 (1): 245–51. doi:10.1016/j.bbrc.2007.03.134. PMID 17418098.