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Interferon-induced transmembrane protein 1 is a protein that in humans is encoded by the IFITM1 gene.[1][2] IFITM1 has also recently been designated CD225 (cluster of differentiation 225). This protein has several additional names: fragilis (human homolog of the mouse protein), IFI17 [interferon-induced protein 17], 9-27 [Interferon-inducible protein 9-27] and Leu13.

IFITM1 is a member of the IFITM family (Interferon-induced transmembrane protein) which is encoded by IFITM genes. The human IFITM genes locate on chromosome 11 and have four members: IFITM1, IFITM2, IFITM3 and IFITM5.[3] While the mouse Ifitm genes locate on chromosome 7 and 16 and have six members: Ifitm1, Ifitm2, Ifitm3, Ifitm5, Ifitm6 and Ifitm7.

Molecular biology

The IFITM1 gene is located on the Watson (plus) strand of the short arm of chromosome 11 (11p15.5) and is 3,956 bases in length. The encoded protein has 125 amino acids (molecular weight 13.964 kDa).

It is an intrinsic membrane protein and is predicted to cross the membrane several times.

Structure and function

IFITM proteins have a short N-terminal and C-terminal domain, two transmembrane domains (TM1 and TM2) and a short cytoplasmic domain. The first transmembrane domain (TM1) and the cytoplasmic domain are conserved among different IFITM proteins in human and mouse.[4] In the absence of interferon stimulation, IFITM proteins can express broadly in tissues and cell lines. In human, ITITM1, IFITM2 and IFITM3 are able to express in different tissues and cells while the expression of IFITM5 is limited to osteoblasts.[5] The type I and II interferon induce IFITM proteins expression significantly. IFITM proteins are involved in the physiological process of immune response signaling, germ cell maturation and development.[6]


The gene is induced by interferon and the protein forms part of the signaling pathway.

Antiviral function of IFITM proteins

By using genomic screening for cellular factors which are involved in influenza A virus life cycle such as entry, replication and release, IFITM proteins have been identified as antiviral restriction factors for influenza A virus replication. Knockout IFITM3 increased influenza virus A replication and overexpression IFITM3 inhibits influenza virus A replication.[7] In addition to replication competent influenza A virus, IFITM proteins were able to inhibit retrovirus based psedotyped influenza A virus, indicating that IFITM protein inhibit influenza A virus at the early step of life cycle, may occur in the entry and fusion steps.

IFITM proteins also are able to inhibit several other enveloped viruses infection that belong to different virus families. These virus include flaviviruses (dengue virus and West Nile virus), filoviruses (Marburg virus and Ebola virus) coronaviruses (SARS coronavirus) and lentivirus (Human immunodeficiency virus).[8] However, IFITM proteins did not affect alphaviruses, arenaviruses and murine leukaemia virus infection.

Potential mechanisms.IFITM proteins inhibit viral membrane and cellular endosomal or lyso¬somal vesicles membrane fusion by modify lipid components or fluidity. IFITM proteins blocked the creation of hemifusion between viral membrane and cellular membrane. Furthermore, IFITM proteins reduced membrane fluidity and affected membrane curvature to restrict viral membrane fusion with the cellular membrane.[9] In addition, IFITM3 interacted with the cellular cholesterol regulatory proteins Vesicle-membrane-protein-associated protein A (VAPA) and oxysterol-binding protein (OSBP) to induce intracellular cholesterol accumulation, which in turn blocked viral membrane and vesicles membrane fusion.[10]


  1. Deblandre GA, Marinx OP, Evans SS, Majjaj S, Leo O, Caput D, Huez GA, Wathelet MG (Nov 1995). "Expression cloning of an interferon-inducible 17-kDa membrane protein implicated in the control of cell growth". J Biol Chem. 270 (40): 23860–6. doi:10.1074/jbc.270.40.23860. PMID 7559564.
  2. "Entrez Gene: IFITM1 interferon induced transmembrane protein 1 (9-27)".
  3. Hickford D, Frankenberg S, Shaw G, Renfree MB (2012). "Evolution of vertebrate interferon inducible transmembrane proteins". BMC Genomics. 13: 155. doi:10.1186/1471-2164-13-155. PMC 3424830. PMID 22537233.
  4. Yount JS, Moltedo B, Yang YY, Charron G, Moran TM, López CB, Hang HC (August 2010). "Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3". Nat. Chem. Biol. 6 (8): 610–4. doi:10.1038/nchembio.405. PMC 2928251. PMID 20601941.
  5. Tanaka SS, Yamaguchi YL, Tsoi B, Lickert H, Tam PP (December 2005). "IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion". Dev. Cell. 9 (6): 745–56. doi:10.1016/j.devcel.2005.10.010. PMID 16326387.
  6. Lewin AR, Reid LE, McMahon M, Stark GR, Kerr IM (July 1991). "Molecular analysis of a human interferon-inducible gene family". Eur. J. Biochem. 199 (2): 417–23. doi:10.1111/j.1432-1033.1991.tb16139.x. PMID 1906403.
  7. Feeley EM, Sims JS, John SP, Chin CR, Pertel T, Chen LM, Gaiha GD, Ryan BJ, Donis RO, Elledge SJ, Brass AL (October 2011). "IFITM3 inhibits influenza A virus infection by preventing cytosolic entry". PLoS Pathog. 7 (10): e1002337. doi:10.1371/journal.ppat.1002337. PMC 3203188. PMID 22046135.
  8. Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ (December 2009). "The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus". Cell. 139 (7): 1243–54. doi:10.1016/j.cell.2009.12.017. PMC 2824905. PMID 20064371.
  9. Li K, Markosyan RM, Zheng YM, Golfetto O, Bungart B, Li M, Ding S, He Y, Liang C, Lee JC, Gratton E, Cohen FS, Liu SL (January 2013). "IFITM proteins restrict viral membrane hemifusion". PLoS Pathog. 9 (1): e1003124. doi:10.1371/journal.ppat.1003124. PMC 3554583. PMID 23358889.
  10. Amini-Bavil-Olyaee S, Choi YJ, Lee JH, Shi M, Huang IC, Farzan M, Jung JU (April 2013). "The Antiviral Effector IFITM3 Disrupts Intracellular Cholesterol Homeostasis to Block Viral Entry". Cell Host Microbe. 13 (4): 452–64. doi:10.1016/j.chom.2013.03.006. PMC 3646482. PMID 23601107.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.