Interferon-induced transmembrane protein 1 is aprotein that in humans is encoded by theIFITM1gene.[3][4] IFITM1 has also recently been designatedCD225 (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.[5] While the mouse Ifitm genes locate on chromosome 7 and 16 and have six members: Ifitm1,Ifitm2,Ifitm3,Ifitm5,Ifitm6 andIfitm7.
The IFITM1 gene is located on the Watson (plus) strand of the short arm ofchromosome 11 (11p15.5) and is 3,956 bases in length. The encoded protein has 125amino acids (molecular weight 13.964kDa).
It is an intrinsic membrane protein and is predicted to cross the membrane several times.
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.[6] 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.[7] 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.[8]
IFITM proteins have been identified as cell-autonomous proteins that suppress the early stages ofviral replication.[9] Knockout ofIFITM3 increasedinfluenza A virus replication, and overexpression of IFITM3 inhibits influenza virus A replication.[10] 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 inhibitviral membrane and cellularendosomal orlysosomalvesicle membrane fusion by modifying their lipid components or fluidity. IFITM proteins block the hemifusion stage of entry,[9] an intermediate stage in which portions the outer membranes of the target cell and the viral envelope mix prior to completion of fusion.[12] 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 proteinsvesicle associated membrane protein A (VAPA) andoxysterol binding protein (OSBP) to induce intracellular cholesterol accumulation, which in turn blocks viral membrane and vesicle membrane fusion.[13]
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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.PMID14667819.
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.PMID15808405.
