|Interferon induced transmembrane protein 1|
|Symbols||; 9-27; CD225; DSPA2a; IFI17; LEU13|
|RNA expression pattern|
Interferon-induced transmembrane protein 1 is a protein that in humans is encoded by the IFITM1 gene. 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. While the mouse Ifitm genes locate on chromosome 7 and 16 and have six members: Ifitm1, Ifitm2, Ifitm3, Ifitm5, Ifitm6 and Ifitm7.
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. 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. 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.
The gene is induced by interferon and the protein forms part of the signaling pathway.
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. 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 family. These virus include flaviviruses (dengue virus and West Nile virus), filoviruses (Marburg virus and Ebola virus) coronaviruses (SARS coronavirus) and lentivirus (Human immunodeficiency virus). 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. 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.
- 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.
- "Entrez Gene: IFITM1 interferon induced transmembrane protein 1 (9-27)".
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. PMID 23601107.
- Bradbury LE, Kansas GS, Levy S, et al. (1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules.". J. Immunol. 149 (9): 2841–50. PMID 1383329.
- Takahashi S, Doss C, Levy S, Levy R (1990). "TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen.". J. Immunol. 145 (7): 2207–13. PMID 2398277.
- Reid LE, Brasnett AH, Gilbert CS, et al. (1989). "A single DNA response element can confer inducibility by both alpha- and gamma-interferons.". Proc. Natl. Acad. Sci. U.S.A. 86 (3): 840–4. doi:10.1073/pnas.86.3.840. PMC 286573. PMID 2492664.
- Kelly JM, Gilbert CS, Stark GR, Kerr IM (1986). "Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha- and gamma-interferons.". Eur. J. Biochem. 153 (2): 367–71. doi:10.1111/j.1432-1033.1985.tb09312.x. PMID 3935435.
- Friedman RL, Manly SP, McMahon M, et al. (1984). "Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.". Cell 38 (3): 745–55. doi:10.1016/0092-8674(84)90270-8. PMID 6548414.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kita K, Sugaya S, Zhai L, et al. (2003). "Involvement of LEU13 in interferon-induced refractoriness of human RSa cells to cell killing by X rays.". Radiat. Res. 160 (3): 302–8. doi:10.1667/RR3039. PMID 12926988.
- Lehner B, Semple JI, Brown SE, et al. (2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region.". Genomics 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Akyerli CB, Beksac M, Holko M, et al. (2005). "Expression of IFITM1 in chronic myeloid leukemia patients.". Leuk. Res. 29 (3): 283–6. doi:10.1016/j.leukres.2004.07.007. PMID 15661263.
- Yang Y, Lee JH, Kim KY, et al. (2005). "The interferon-inducible 9-27 gene modulates the susceptibility to natural killer cells and the invasiveness of gastric cancer cells.". Cancer Lett. 221 (2): 191–200. doi:10.1016/j.canlet.2004.08.022. PMID 15808405.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.