ArticleThe Journal of biological chemistry2014
Phosphorylation of the antiviral protein interferon-inducible transmembrane protein 3 (IFITM3) dually regulates its endocytosis and ubiquitination.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 142 citations in OpenAlex.
- Article
- IFITM1 and IFITM3 cooperate to restrict virus entry in endolysosomes.Journal of virology · 2026Article
- Interferon-induced transmembrane proteins in cancer and virus biology: a membrane perspective.mBio · 2026Review
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- Interferon-induced transmembrane proteins: membrane gatekeepers of fusion and infection.Frontiers in cellular and infection microbiology · 2026Review
- IFITM3 at the viral fusion-pore checkpoint: membrane energetics and entry-route-dependent outcomes.Frontiers in immunology · 2026Review
- IFITM1 and IFITM3 cooperate to restrict virus entry in endolysosomes.bioRxiv : the preprint server for biology · 2025Article
- Review
- IFITM2 Modulates Endocytosis Maintaining Neural Stem Cells in Developing Neocortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Attenuation of IFITM proteins' antiviral activity through sequestration into intraluminal vesicles of late endosomes.Frontiers in immunology · 2025Article
- Alternative splicing expands the antiviral IFITM repertoire in Chinese rufous horseshoe bats.PLoS pathogens · 2024Article
- Review
- The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies.Viruses · 2024Review
- Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs.Pathogens (Basel, Switzerland) · 2024Review
- FOXP3Nature communications · 2024Article
- Functional characterization of endocytic signals in the SynDIG/PRRT family members SynDIG1 and SynDIG4 in heterologous cells and neurons.Frontiers in cellular neuroscience · 2024Article
- Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.Frontiers in cellular and infection microbiology · 2024Article
- The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81.Emerging microbes & infections · 2023Article
- Discovery and Characterization of IFITMViruses · 2023Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans. IFITM3 localizes to endolysosomes where it prevents virus fusion, although mechanisms controlling its trafficking to this cellular compartment are not fully understood. We determined that both mouse and human IFITM3 are phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr(20)) and that mouse IFITM3 is also phosphorylated on the non-conserved Tyr(27). Phosphorylation led to a cellular redistribution of IFITM3, including plasma membrane accumulation. Mutation of Tyr(20) caused a similar redistribution of IFITM3 and resulted in decreased antiviral activity against influenza virus, whereas Tyr(27) mutation of mouse IFITM3 showed minimal effects on localization or activity. Using FYN knockout cells, we also found that IFITM3 phosphorylation is not a requirement for its antiviral activity. Together, these results indicate that Tyr(20) is part of an endocytosis signal that can be blocked by phosphorylation or by mutation of this residue. Further mutagenesis narrowed this endocytosis-controlling region to four residues conforming to a YXXΦ (where X is any amino acid and Φ is Val, Leu, or Ile) endocytic motif that, when transferred to CD4, resulted in its internalization from the cell surface. Additionally, we found that phosphorylation of IFITM3 by FYN and mutagenesis of Tyr(20) both resulted in decreased IFITM3 ubiquitination. Overall, these results suggest that modification of Tyr(20) may serve in a cellular checkpoint controlling IFITM3 trafficking and degradation and demonstrate the complexity of posttranslational regulation of IFITM3.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.