Biology:IFITM1
 Generic protein structure example |
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 humans and mice.[4] In the absence of interferon stimulation, IFITM proteins can express broadly in tissues and cell lines. In humans, IFITM1, 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]
Biochemistry
The gene is induced by interferon and the protein forms part of the signaling pathway.
Antiviral function of IFITM proteins
IFITM proteins have been identified as cell-autonomous proteins that suppress the early stages of viral replication.[7] Knockout of IFITM3 increased influenza A virus replication, and overexpression of IFITM3 inhibits influenza virus A replication.[8] In addition to replication competent influenza A virus, IFITM proteins were able to inhibit retrovirus based pseudotyped 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 infection with other enveloped viruses 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 lentiviruses (Human Immunodeficiency Virus (HIV)).[9] However, IFITM proteins did not affect alphavirus, arenavirus, or murine leukaemia virus infection.
IFITM proteins inhibit viral membrane and cellular endosomal or lysosomal vesicle membrane fusion by modifying their lipid components or fluidity. IFITM proteins block the hemifusion stage of entry,[7] an intermediate stage in which portions the outer membranes of the target cell and the viral envelope mix prior to completion of fusion.[10] Furthermore, IFITM proteins reduced membrane fluidity and affected membrane curvature to restrict viral membrane fusion with the cellular membrane.[7] In addition, IFITM3 interacted with the cellular cholesterol regulatory proteins vesicle associated membrane protein A (VAPA) and oxysterol binding protein (OSBP) to induce intracellular cholesterol accumulation, which in turn blocks viral membrane and vesicle membrane fusion.[11]
References
- ↑ "Expression cloning of an interferon-inducible 17-kDa membrane protein implicated in the control of cell growth". J Biol Chem 270 (40): 23860–6. Nov 1995. doi:10.1074/jbc.270.40.23860. PMID 7559564.
- ↑ "Entrez Gene: IFITM1 interferon induced transmembrane protein 1 (9-27)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8519.
- ↑ "Evolution of vertebrate interferon inducible transmembrane proteins". BMC Genomics 13: 155. 2012. doi:10.1186/1471-2164-13-155. PMID 22537233.
- ↑ "Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3". Nat. Chem. Biol. 6 (8): 610–4. August 2010. doi:10.1038/nchembio.405. PMID 20601941.
- ↑ "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. December 2005. doi:10.1016/j.devcel.2005.10.010. PMID 16326387.
- ↑ "Molecular analysis of a human interferon-inducible gene family". Eur. J. Biochem. 199 (2): 417–23. July 1991. doi:10.1111/j.1432-1033.1991.tb16139.x. PMID 1906403.
- ↑ 7.0 7.1 7.2 "IFITM proteins restrict viral membrane hemifusion". PLOS Pathog. 9 (1): e1003124. January 2013. doi:10.1371/journal.ppat.1003124. PMID 23358889.
- ↑ "IFITM3 inhibits influenza A virus infection by preventing cytosolic entry". PLOS Pathog. 7 (10): e1002337. October 2011. doi:10.1371/journal.ppat.1002337. PMID 22046135.
- ↑ "The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus". Cell 139 (7): 1243–54. December 2009. doi:10.1016/j.cell.2009.12.017. PMID 20064371.
- ↑ Harrison, Stephen C (July 2008). "Viral membrane fusion". Nat Struct Mol Biol 15 (7): 690–8. doi:10.1038/nsmb.1456. PMID 18596815.
- ↑ "The Antiviral Effector IFITM3 Disrupts Intracellular Cholesterol Homeostasis to Block Viral Entry". Cell Host Microbe 13 (4): 452–64. April 2013. doi:10.1016/j.chom.2013.03.006. PMID 23601107.
Further reading
- "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. 1992. doi:10.4049/jimmunol.149.9.2841. PMID 1383329.
- "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. 1990. doi:10.4049/jimmunol.145.7.2207. PMID 2398277.
- "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. 1989. doi:10.1073/pnas.86.3.840. PMID 2492664. Bibcode: 1989PNAS...86..840R.
- "Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha- and gamma-interferons.". Eur. J. Biochem. 153 (2): 367–71. 1986. doi:10.1111/j.1432-1033.1985.tb09312.x. PMID 3935435.
- "Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.". Cell 38 (3): 745–55. 1984. doi:10.1016/0092-8674(84)90270-8. PMID 6548414.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Involvement of LEU13 in interferon-induced refractoriness of human RSa cells to cell killing by X rays.". Radiat. Res. 160 (3): 302–8. 2003. doi:10.1667/RR3039. PMID 12926988. Bibcode: 2003RadR..160..302K.
- "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. 2004. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Expression of IFITM1 in chronic myeloid leukemia patients.". Leuk. Res. 29 (3): 283–6. 2005. doi:10.1016/j.leukres.2004.07.007. PMID 15661263.
- "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. 2005. doi:10.1016/j.canlet.2004.08.022. PMID 15808405.
- "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
External links
- IFITM1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
 |  |
