Gene Symbol: Ifitm3
Description: interferon induced transmembrane protein 3
Alias: 1110004C05Rik, Cd225, Cdw217, DSPA2b, Fgls, IP15, mil-1, interferon-induced transmembrane protein 3, dispanin subfamily A member 2b, fragilis protein, ifitm-like protein 1, interferon-inducible protein 15
Species: mouse
Products:     Ifitm3

Top Publications

  1. Huang I, Bailey C, Weyer J, Radoshitzky S, Becker M, Chiang J, et al. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog. 2011;7:e1001258 pubmed publisher
    ..of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1...
  2. Saitou M, Barton S, Surani M. A molecular programme for the specification of germ cell fate in mice. Nature. 2002;418:293-300 pubmed
    ..The stella positive nascent germ cells exhibit repression of homeobox genes, which may explain their escape from a somatic cell fate and the retention of pluripotency. ..
  3. Tanaka S, Yamaguchi Y, Tsoi B, Lickert H, Tam P. IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion. Dev Cell. 2005;9:745-56 pubmed
    ..In contrast, Ifitm3, which is expressed in migratory PGCs, is sufficient to confer autonomous PGC-like homing properties to somatic ..
  4. Wee Y, Roundy K, Weis J, Weis J. Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function. Innate Immun. 2012;18:834-45 pubmed publisher
    ..Co-immunoprecipitation of Ifitm3 with Atp6v0b demonstrated a direct interaction between the Ifitm proteins and the v-ATPase...
  5. Wakim L, Gupta N, Mintern J, Villadangos J. Enhanced survival of lung tissue-resident memory CD8? T cells during infection with influenza virus due to selective expression of IFITM3. Nat Immunol. 2013;14:238-45 pubmed publisher
    ..we found that lung T(RM) cells selectively maintained expression of the interferon-induced transmembrane protein IFITM3, a protein that confers broad resistance to viral infection...
  6. Yount J, Karssemeijer R, Hang H. S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3 (IFITM3)-mediated resistance to influenza virus. J Biol Chem. 2012;287:19631-41 pubmed publisher
    The interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that inhibits infection by influenza virus and many other pathogenic viruses...
  7. Brass A, Huang I, Benita Y, John S, Krishnan M, Feeley E, et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009;139:1243-54 pubmed publisher
    ..Collectively this work identifies a family of antiviral restriction factors that mediate cellular innate immunity to at least three major human pathogens...
  8. Bailey C, Huang I, Kam C, Farzan M. Ifitm3 limits the severity of acute influenza in mice. PLoS Pathog. 2012;8:e1002909 pubmed publisher
    ..We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus...
  9. Everitt A, Clare S, Pertel T, John S, Wash R, Smith S, et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012;484:519-23 pubmed publisher
    ..Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo...

More Information


  1. Lange U, Saitou M, Western P, Barton S, Surani M. The fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice. BMC Dev Biol. 2003;3:1 pubmed
    ..Furthermore, its evolutionary conservation suggests that it probably plays a critical role in all mammals. Detailed analysis of these genes may also elucidate the role of interferons as signalling molecules during development. ..
  2. Chesarino N, McMichael T, Hach J, Yount J. Phosphorylation of the antiviral protein interferon-inducible transmembrane protein 3 (IFITM3) dually regulates its endocytosis and ubiquitination. J Biol Chem. 2014;289:11986-92 pubmed publisher
    Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans...
  3. Lange U, Adams D, Lee C, Barton S, Schneider R, Bradley A, et al. Normal germ line establishment in mice carrying a deletion of the Ifitm/Fragilis gene family cluster. Mol Cell Biol. 2008;28:4688-96 pubmed publisher
    ..Recently, Ifitm1 and Ifitm3 have been suggested to mediate migration of early primordial germ cells (PGCs), a process that is little ..
  4. Ibi D, Nagai T, Nakajima A, Mizoguchi H, Kawase T, Tsuboi D, et al. Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice. Glia. 2013;61:679-93 pubmed publisher
    Interferon-induced transmembrane protein 3 (IFITM3) ıplays a crucial role in the antiviral responses of Type I interferons (IFNs)...
  5. Yamada K. [Neurodevelopmental impairment following neonatal immune challenge in mice]. Nihon Yakurigaku Zasshi. 2013;142:221-5 pubmed
  6. Lin T, Chin C, Everitt A, Clare S, Perreira J, Savidis G, et al. Amphotericin B increases influenza A virus infection by preventing IFITM3-mediated restriction. Cell Rep. 2013;5:895-908 pubmed publisher
    ..Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication...
  7. Han D, Tapia N, Joo J, Greber B, Arauzo Bravo M, Bernemann C, et al. Epiblast stem cell subpopulations represent mouse embryos of distinct pregastrulation stages. Cell. 2010;143:617-27 pubmed publisher
    ..Our findings suggest that the rare ability of EpiSCs to contribute to chimeras is due to the presence of the minor EpiSC fraction representing the early epiblast. ..
  8. Bailey C, Kondur H, Huang I, Farzan M. Interferon-induced transmembrane protein 3 is a type II transmembrane protein. J Biol Chem. 2013;288:32184-93 pubmed publisher
    ..Here we determined the topology of murine Ifitm3. We found that the N terminus of Ifitm3 could be stained by antibodies at the cell surface but that this ..
  9. Hara K, Kanai Azuma M, Uemura M, Shitara H, Taya C, Yonekawa H, et al. Evidence for crucial role of hindgut expansion in directing proper migration of primordial germ cells in mouse early embryogenesis. Dev Biol. 2009;330:427-39 pubmed publisher
    ..Therefore, these data indicate that hindgut morphogenic movement is crucial for directing PGC movement toward the embryonic gut side, but not for their relocation from the mesoderm into the endoderm. ..
  10. Sennett R, Wang Z, Rezza A, Grisanti L, Roitershtein N, Sicchio C, et al. An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin. Dev Cell. 2015;34:577-91 pubmed publisher
    ..Finally, we share all data in an interactive, searchable companion website. Our study provides an overarching view of signaling within the entire embryonic skin and captures a molecular snapshot of HF progenitors and their niche. ..
  11. Ohinata Y, Payer B, O Carroll D, Ancelin K, Ono Y, Sano M, et al. Blimp1 is a critical determinant of the germ cell lineage in mice. Nature. 2005;436:207-13 pubmed
    ..Furthermore, our genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors. ..
  12. Ropolo A, Tomasini R, Grasso D, Dusetti N, Cerquetti M, Iovanna J, et al. Cloning of IP15, a pancreatitis-induced gene whose expression inhibits cell growth. Biochem Biophys Res Commun. 2004;319:1001-9 pubmed
    We describe the cloning and expression of the mouse gene interferon-inducible-protein 15 (IP15), whose activation is related to the acute phase of experimental pancreatitis...
  13. Feng W, Leach S, Tipney H, Phang T, Geraci M, Spritz R, et al. Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences. PLoS ONE. 2009;4:e8066 pubmed publisher
    ..Overall, our studies provide a valuable resource for probing orofacial development and a robust dataset for bioinformatic analysis of spatial and temporal gene expression changes during embryogenesis. ..
  14. Jia R, Ding S, Pan Q, Liu S, Qiao W, Liang C. The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity. PLoS ONE. 2015;10:e0118794 pubmed publisher
    ..The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization. ..
  15. Bosman E, Lawson K, Debruyn J, Beek L, Francis A, Schoonjans L, et al. Smad5 determines murine amnion fate through the control of bone morphogenetic protein expression and signalling levels. Development. 2006;133:3399-409 pubmed
    ..These results support a model in which loss of Smad5 results paradoxically in gain of Bmp function defects in the amnion. ..
  16. de Sousa Lopes S, Roelen B, Monteiro R, Emmens R, Lin H, Li E, et al. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev. 2004;18:1838-49 pubmed
    ..We propose a model in which direct signaling to proximal epiblast is supplemented by an obligatory indirect BMP-dependent signal via the VE. ..
  17. Maeda C, Sato S, Hattori N, Tanaka S, Yagi S, Shiota K. DNA hypomethylation circuit of the mouse oocyte-specific histone H1foo gene in female germ cell lineage. Biol Reprod. 2008;78:816-21 pubmed publisher
    ..5, in mature oocytes, and after fertilization, in E3.5 blastocysts. In comparison, male germ cells acquired methylation beyond E18.5. These data demonstrate a continuously unmethylated circuit at the H1foo locus in the female germline. ..
  18. Zhong J, Cui X, Shi Y, Guo S, Liu Y, Liu F, et al. [Effects of jin chai antiviral capsule on IFITM3 expression in mice]. Yao Xue Xue Bao. 2012;47:904-8 pubmed
    ..and Western blot technique were used to detect the virus load and the interferoninducible transmembrane protein3 (IFITM3) in lung of mice at the 1st day, 3rd day, 5th day and 7th day after affected...
  19. Tanaka S, Yamaguchi Y, Steiner K, Nakano T, Nishinakamura R, Kwan K, et al. Loss of Lhx1 activity impacts on the localization of primordial germ cells in the mouse. Dev Dyn. 2010;239:2851-9 pubmed publisher
    ..Lhx1 therefore may influence the localization of PGCs by modulating Ifitm1-mediated repulsive activity. ..
  20. Matsui Y, Okamura D. Mechanisms of germ-cell specification in mouse embryos. Bioessays. 2005;27:136-43 pubmed
    ..This raises the possibility that ES cells, as well as, possibly, pluripotential cells in preimplantation embryos, are more closely related to the PGC precursors than pluripotential cells after implantation. ..
  21. Bialecka M, Young T, Chuva de Sousa Lopes S, ten Berge D, Sanders A, Beck F, et al. Cdx2 contributes to the expansion of the early primordial germ cell population in the mouse. Dev Biol. 2012;371:227-34 pubmed publisher
    ..Since PGC residence within the posterior growth zone is a mouse-specific feature, our data suggest that mouse PGCs opportunistically became dependent on the axial progenitor niche. ..
  22. Sun J, Ting M, Ishii M, Maxson R. Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse. Dev Biol. 2016;417:11-24 pubmed publisher
    ..We also noted a reduction in the expression of Wnt5a and an increase in the expression in Bmp4 in such tissues in Msx1(-/-);Msx2(-/-) mutants, both known effectors of PGC development. ..
  23. Stacey M, Clare S, Clement M, Marsden M, Abdul Karim J, Kane L, et al. The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis. J Clin Invest. 2017;127:1463-1474 pubmed publisher
    The antiviral restriction factor IFN-induced transmembrane protein 3 (IFITM3) inhibits cell entry of a number of viruses, and genetic diversity within IFITM3 determines susceptibility to viral disease in humans...
  24. Li S, Fu B, Wang L, Dorf M. ZMPSTE24 Is Downstream Effector of Interferon-Induced Transmembrane Antiviral Activity. DNA Cell Biol. 2017;36:513-517 pubmed publisher
    ..In vivo studies with zmpste24-deficient mice demonstrate the importance of ZMPSTE24 for antiviral defense. ..
  25. Li D, Peng Z, Tang H, Wei P, Kong X, Yan D, et al. KLF4-mediated negative regulation of IFITM3 expression plays a critical role in colon cancer pathogenesis. Clin Cancer Res. 2011;17:3558-68 pubmed publisher
    b>IFITM3, an IFN-inducible gene, is overexpressed in human colorectal cancer...
  26. Tanaka S, Matsui Y. Developmentally regulated expression of mil-1 and mil-2, mouse interferon-induced transmembrane protein like genes, during formation and differentiation of primordial germ cells. Mech Dev. 2002;119 Suppl 1:S261-7 pubmed
    ..5-7.5 days post coitum. In migrating PGCs, mil-1 expression was continuously observed and mil-2 expression was first detected during germ cell differentiation. ..
  27. Everitt A, Clare S, McDonald J, Kane L, Harcourt K, Ahras M, et al. Defining the range of pathogens susceptible to Ifitm3 restriction using a knockout mouse model. PLoS ONE. 2013;8:e80723 pubmed publisher
    ..We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model...
  28. Chang S, Park H, Dong C. Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem. 2006;281:35603-7 pubmed
    ..Our study not only for the first time reveals an immediate signaling mechanism downstream of an IL-17 family receptor but also has implications in therapeutic treatment of various immune diseases. ..
  29. Ben Haim N, Lu C, Guzman Ayala M, Pescatore L, Mesnard D, Bischofberger M, et al. The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4. Dev Cell. 2006;11:313-23 pubmed
    ..Based on mathematical modeling, we discuss how these sequential loops control cell fate. ..
  30. Smith R, Young J, Weis J, Weis J. Expression of the mouse fragilis gene products in immune cells and association with receptor signaling complexes. Genes Immun. 2006;7:113-21 pubmed
    ..The mouse functional equivalent to human Leu-13 may not be single gene product, but instead may require the contribution of multiple fragilis proteins. ..
  31. Tanaka S, Nagamatsu G, Tokitake Y, Kasa M, Tam P, Matsui Y. Regulation of expression of mouse interferon-induced transmembrane protein like gene-3, Ifitm3 (mil-1, fragilis), in germ cells. Dev Dyn. 2004;230:651-9 pubmed
    Mouse interferon-induced transmembrane protein (IFITM) gene, Ifitm3 (previously known as mil-1 and fragilis), is expressed in primordial germ cells (PGCs), in their precursors, and in germ cells of the fetal gonads (Saitou et al...
  32. Saitou M, Payer B, Lange U, Erhardt S, Barton S, Surani M. Specification of germ cell fate in mice. Philos Trans R Soc Lond B Biol Sci. 2003;358:1363-70 pubmed
    ..While these molecules are also detected in mature oocytes as maternally inherited factors, their early role is to regulate development and maintain pluripotency, and they do not serve the role of classical germline determinants. ..
  33. Mikedis M, Downs K. Widespread but tissue-specific patterns of interferon-induced transmembrane protein 3 (IFITM3, FRAGILIS, MIL-1) in the mouse gastrula. Gene Expr Patterns. 2013;13:225-39 pubmed publisher
    Interferon-induced transmembrane protein 3 (IFITM3; FRAGILIS; MIL-1) is part of a larger family of important small interferon-induced transmembrane genes and proteins involved in early development, cell adhesion, and cell proliferation, ..
  34. Yu M, Qi W, Huang Z, Zhang K, Ye J, Liu R, et al. Expression profile and histological distribution of IFITM1 and IFITM3 during H9N2 avian influenza virus infection in BALB/c mice. Med Microbiol Immunol. 2015;204:505-14 pubmed publisher
    ..Here, we investigated the expression patterns and tissue distribution of IFITM1 and IFITM3 in BALB/c mice by infection with H9N2 AIV strains with only a PB2 residue 627 difference...
  35. Savidis G, Perreira J, Portmann J, Meraner P, Guo Z, Green S, et al. The IFITMs Inhibit Zika Virus Replication. Cell Rep. 2016;15:2323-30 pubmed publisher
    ..Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle...
  36. Poddar S, Hyde J, Gorman M, Farzan M, Diamond M. The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses. J Virol. 2016;90:8780-94 pubmed publisher
    ..b>IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, ..