IFITM3

Interferon-induced transmembrane protein 3 (IFITM3) is a protein that in humans is encoded by the IFITM3 gene.[5][6][7] It plays a critical role in the immune system's defense against Swine Flu, where heightened levels of IFITM3 keep viral levels low, and the removal of IFITM3 allows the virus to multiply unchecked.[8] This observation has been further advanced by a recent study from Paul Kellam's lab that shows that a single nucleotide polymorphism in the human IFITM3 gene purported to increase influenza susceptibility is overrepresented in people hospitalised with pandemic H1N1.[9] The prevalence of this mutation is thought to be approximately 1/400 in European populations.[9][10]

IFITM3
Identifiers
Aliases	IFITM3, 1-8U, DSPA2b, IP15, interferon induced transmembrane protein 3
External IDs	OMIM: 605579 MGI: 1913391 HomoloGene: 136199 GeneCards: IFITM3
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.5 Start 319,676 bp[1] End 327,537 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F5 Start 141,009,586 bp[2] End 141,010,770 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • integral component of membrane • endosome • membrane • late endosome membrane • cell membrane • lysosomal membrane • lysosome • macromolecular complex Biological process • negative regulation of viral entry into host cell • response to interferon-gamma • immune system process • response to virus • response to interferon-beta • response to biotic stimulus • negative regulation of viral genome replication • type I interferon signaling pathway • immune response • response to interferon-alpha • innate immune system • negative regulation of viral transcription • defense response to virus Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10410	66141
Ensembl	ENSG00000142089	ENSMUSG00000025492
UniProt	Q01628	Q9CQW9
RefSeq (mRNA)	NM_021034	NM_025378
RefSeq (protein)	NP_066362	NP_079654
Location (UCSC)	Chr 11: 0.32 – 0.33 Mb	Chr 7: 141.01 – 141.01 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Model organisms

Ifitm3 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Salmonella infection	Normal[11]
Citrobacter infection	Normal[12]
All tests and analysis from[13][14]

Model organisms have been used in the study of IFITM3 function. A conditional knockout mouse line, called Ifitm3^tm1Masu[15][16] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty four tests were carried out on mutant mice, but no significant abnormalities were observed.[13] However, challenge with influenza A virus indicated that these mice display increased viral susceptibility.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000142089 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025492 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lewin AR, Reid LE, McMahon M, Stark GR, Kerr IM (Aug 1991). "Molecular analysis of a human interferon-inducible gene family". Eur J Biochem. 199 (2): 417–423. doi:10.1111/j.1432-1033.1991.tb16139.x. PMID 1906403.
6. Tanaka SS, Yamaguchi YL, Tsoi B, Lickert H, Tam PP (Dec 2005). "IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion". Dev Cell. 9 (6): 745–756. doi:10.1016/j.devcel.2005.10.010. PMID 16326387.
7. "Entrez Gene: IFITM3 interferon induced transmembrane protein 3 (1-8U)".
8. "Natural swine flu defence found".
9. Everitt A.R.; et al. (March 2012). "IFITM3 restricts the morbidity and mortality associated with influenza". Nature. 484 (7395): 519–23. doi:10.1038/nature10921. PMC 3648786. PMID 22446628.
10. "Gene flaw linked to serious flu risk".
11. "Salmonella infection data for Ifitm3". Wellcome Trust Sanger Institute.
12. "Citrobacter infection data for Ifitm3". Wellcome Trust Sanger Institute.
13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. "International Knockout Mouse Consortium".
16. "Mouse Genome Informatics".
17. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
18. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
19. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Vaarala MH, Porvari K, Kyllönen A, Vihko P (2000). "Differentially expressed genes in two LNCaP prostate cancer cell lines reflecting changes during prostate cancer progression". Lab. Invest. 80 (8): 1259–1268. doi:10.1038/labinvest.3780134. PMID 10950117.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–292. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• 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): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• 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): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–D418. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.