TRIM25

Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.[5][6]

TRIM25
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTRIM25, EFP, RNF147, Z147, ZNF147, tripartite motif containing 25
External IDsOMIM: 600453 MGI: 102749 HomoloGene: 48325 GeneCards: TRIM25
EC number2.3.2.27
Orthologs
SpeciesHumanMouse
Entrez

7706

217069

Ensembl

ENSG00000121060

ENSMUSG00000000275

UniProt

Q14258

Q61510

RefSeq (mRNA)

NM_005082

NM_009546

RefSeq (protein)

NP_005073

NP_033572

Location (UCSC)Chr 17: 56.84 – 56.91 MbChr 11: 88.89 – 88.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.[7] 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.[6]

Domain Architecture

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.[8] The SPRY domain is required for substrate recruitment.[9] 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.[10]

TRIM25 functions

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.[11]

Viral escape

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.[12] Without this ubiquitination, there won’t be IFN production.

References

  1. GRCh38: Ensembl release 89: ENSG00000121060 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000000275 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. "Entrez Gene: TRIM25 tripartite motif-containing 25".
  7. 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 4012390. PMID 24015671.
  8. Haik KG (Jul 1985). "Visual difficulties from video display terminals". Southern Medical Journal. 78 (7): 887–8. doi:10.1097/00007611-198507000-00031. PMID 4012390.
  9. 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.
  10. 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. PMID 25702035. S2CID 11475584.
  11. 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 2575490. PMID 18948594.
  12. 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 2737813. PMID 19454348.

Further reading


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