ID IFM3_HUMAN Reviewed; 133 AA.
AC Q01628; Q53Y76; Q96HK8; Q96J15;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 24-JUL-2024, entry version 187.
DE RecName: Full=Interferon-induced transmembrane protein 3 {ECO:0000305};
DE AltName: Full=Dispanin subfamily A member 2b;
DE Short=DSPA2b;
DE AltName: Full=Interferon-inducible protein 1-8U;
GN Name=IFITM3 {ECO:0000312|HGNC:HGNC:5414};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1906403; DOI=10.1111/j.1432-1033.1991.tb16139.x;
RA Lewin A.R., Reid L.E., McMahon M., Stark G.R., Kerr I.M.;
RT "Molecular analysis of a human interferon-inducible gene family.";
RL Eur. J. Biochem. 199:417-423(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN SUSCEPTIBILITY TO
RP SEVERE INFLUENZA INFECTION.
RX PubMed=22446628; DOI=10.1038/nature10921;
RA Everitt A.R., Clare S., Pertel T., John S.P., Wash R.S., Smith S.E.,
RA Chin C.R., Feeley E.M., Sims J.S., Adams D.J., Wise H.M., Kane L.,
RA Goulding D., Digard P., Anttila V., Baillie J.K., Walsh T.S., Hume D.A.,
RA Palotie A., Xue Y., Colonna V., Tyler-Smith C., Dunning J., Gordon S.B.,
RA Smyth R.L., Openshaw P.J., Dougan G., Brass A.L., Kellam P.;
RT "IFITM3 restricts the morbidity and mortality associated with influenza.";
RL Nature 484:519-523(2012).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-3.
RC TISSUE=Brain, Cervix, and Vascular endothelial cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION IN VIRAL RESISTANCE.
RX PubMed=20064371; DOI=10.1016/j.cell.2009.12.017;
RA Brass A.L., Huang I.C., Benita Y., John S.P., Krishnan M.N., Feeley E.M.,
RA Ryan B.J., Weyer J.L., van der Weyden L., Fikrig E., Adams D.J.,
RA Xavier R.J., Farzan M., Elledge S.J.;
RT "The IFITM proteins mediate cellular resistance to influenza A H1N1 virus,
RT West Nile virus, and dengue virus.";
RL Cell 139:1243-1254(2009).
RN [9]
RP FUNCTION.
RX PubMed=20534863; DOI=10.1128/jvi.02199-09;
RA Jiang D., Weidner J.M., Qing M., Pan X.B., Guo H., Xu C., Zhang X.,
RA Birk A., Chang J., Shi P.Y., Block T.M., Guo J.T.;
RT "Identification of five interferon-induced cellular proteins that inhibit
RT west nile virus and dengue virus infections.";
RL J. Virol. 84:8332-8341(2010).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INVOLVEMENT IN SUSCEPTIBILITY TO SEVERE
RP INFLUENZA INFECTION.
RX PubMed=20943977; DOI=10.1128/jvi.01328-10;
RA Weidner J.M., Jiang D., Pan X.B., Chang J., Block T.M., Guo J.T.;
RT "Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit
RT vesicular stomatitis virus infection via distinct mechanisms.";
RL J. Virol. 84:12646-12657(2010).
RN [11]
RP INTERACTION WITH SPP1.
RX PubMed=19901966; DOI=10.1038/onc.2009.379;
RA El-Tanani M.K., Jin D., Campbell F.C., Johnston P.G.;
RT "Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed
RT in vivo IFITM3 reduced OPN expression.";
RL Oncogene 29:752-762(2010).
RN [12]
RP PALMITOYLATION AT CYS-71; CYS-72 AND CYS-105.
RX PubMed=20601941; DOI=10.1038/nchembio.405;
RA Yount J.S., Moltedo B., Yang Y.Y., Charron G., Moran T.M., Lopez C.B.,
RA Hang H.C.;
RT "Palmitoylome profiling reveals S-palmitoylation-dependent antiviral
RT activity of IFITM3.";
RL Nat. Chem. Biol. 6:610-614(2010).
RN [13]
RP REVIEW.
RX PubMed=21166591; DOI=10.1089/jir.2010.0112;
RA Siegrist F., Ebeling M., Certa U.;
RT "The small interferon-induced transmembrane genes and proteins.";
RL J. Interferon Cytokine Res. 31:183-197(2011).
RN [14]
RP FUNCTION.
RX PubMed=21177806; DOI=10.1128/jvi.01531-10;
RA Lu J., Pan Q., Rong L., He W., Liu S.L., Liang C.;
RT "The IFITM proteins inhibit HIV-1 infection.";
RL J. Virol. 85:2126-2137(2011).
RN [15]
RP ERRATUM OF PUBMED:21177806.
RA Lu J., Pan Q., Rong L., He W., Liu S.L., Liang C.;
RL J. Virol. 85:4043-4043(2011).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22046135; DOI=10.1371/journal.ppat.1002337;
RA Feeley E.M., Sims J.S., John S.P., Chin C.R., Pertel T., Chen L.M.,
RA Gaiha G.D., Ryan B.J., Donis R.O., Elledge S.J., Brass A.L.;
RT "IFITM3 inhibits influenza A virus infection by preventing cytosolic
RT entry.";
RL PLoS Pathog. 7:E1002337-E1002337(2011).
RN [17]
RP FUNCTION.
RX PubMed=21253575; DOI=10.1371/journal.ppat.1001258;
RA Huang I.C., Bailey C.C., Weyer J.L., Radoshitzky S.R., Becker M.M.,
RA Chiang J.J., Brass A.L., Ahmed A.A., Chi X., Dong L., Longobardi L.E.,
RA Boltz D., Kuhn J.H., Elledge S.J., Bavari S., Denison M.R., Choe H.,
RA Farzan M.;
RT "Distinct patterns of IFITM-mediated restriction of filoviruses, SARS
RT coronavirus, and influenza A virus.";
RL PLoS Pathog. 7:E1001258-E1001258(2011).
RN [18]
RP UBIQUITINATION AT LYS-24; LYS-83; LYS-88 AND LYS-104, PALMITOYLATION,
RP TOPOLOGY, LACK OF GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=22511783; DOI=10.1074/jbc.m112.362095;
RA Yount J.S., Karssemeijer R.A., Hang H.C.;
RT "S-palmitoylation and ubiquitination differentially regulate interferon-
RT induced transmembrane protein 3 (IFITM3)-mediated resistance to influenza
RT virus.";
RL J. Biol. Chem. 287:19631-19641(2012).
RN [19]
RP FUNCTION.
RX PubMed=22479637; DOI=10.1371/journal.pone.0034508;
RA Chan Y.K., Huang I.C., Farzan M.;
RT "IFITM proteins restrict antibody-dependent enhancement of dengue virus
RT infection.";
RL PLoS ONE 7:E34508-E34508(2012).
RN [20]
RP GENE FAMILY.
RX PubMed=22363774; DOI=10.1371/journal.pone.0031961;
RA Sallman Almen M., Bringeland N., Fredriksson R., Schioth H.B.;
RT "The dispanins: a novel gene family of ancient origin that contains 14
RT human members.";
RL PLoS ONE 7:E31961-E31961(2012).
RN [21]
RP FUNCTION, AND INTERACTION WITH VAPA.
RX PubMed=23601107; DOI=10.1016/j.chom.2013.03.006;
RA Amini-Bavil-Olyaee S., Choi Y.J., Lee J.H., Shi M., Huang I.C., Farzan M.,
RA Jung J.U.;
RT "The antiviral effector IFITM3 disrupts intracellular cholesterol
RT homeostasis to block viral entry.";
RL Cell Host Microbe 13:452-464(2013).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-20, AND MUTAGENESIS
RP OF TYR-20; 71-CYS-CYS-72 AND CYS-105.
RX PubMed=26354436; DOI=10.1074/jbc.m115.657346;
RA Narayana S.K., Helbig K.J., McCartney E.M., Eyre N.S., Bull R.A.,
RA Eltahla A., Lloyd A.R., Beard M.R.;
RT "The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3
RT Inhibit Hepatitis C Virus Entry.";
RL J. Biol. Chem. 290:25946-25959(2015).
RN [23]
RP INTERACTION WITH BRI3, AND SUBCELLULAR LOCATION.
RX PubMed=30983867; DOI=10.3906/biy-1805-47;
RA Akiva I., Birguel Iyison N.;
RT "Identification of IFITM3 and MGAT1 as novel interaction partners of BRI3
RT by yeast two-hybrid screening.";
RL Turk. J. Biol. 42:463-470(2018).
RN [24]
RP FUNCTION.
RX PubMed=33239446; DOI=10.1073/pnas.2012197117;
RA Zang R., Case J.B., Yutuc E., Ma X., Shen S., Gomez Castro M.F., Liu Z.,
RA Zeng Q., Zhao H., Son J., Rothlauf P.W., Kreutzberger A.J.B., Hou G.,
RA Zhang H., Bose S., Wang X., Vahey M.D., Mani K., Griffiths W.J.,
RA Kirchhausen T., Fremont D.H., Guo H., Diwan A., Wang Y., Diamond M.S.,
RA Whelan S.P.J., Ding S.;
RT "Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking
RT membrane fusion.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:32105-32113(2020).
RN [25]
RP FUNCTION, MUTAGENESIS OF TYR-20; LEU-23; 59-VAL--MET-68; 61-SER--THR-65;
RP 71-CYS-CYS-72 AND CYS-105, AND SUBCELLULAR LOCATION.
RX PubMed=33270927; DOI=10.15252/embj.2020106501;
RA Shi G., Kenney A.D., Kudryashova E., Zani A., Zhang L., Lai K.K.,
RA Hall-Stoodley L., Robinson R.T., Kudryashov D.S., Compton A.A., Yount J.S.;
RT "Opposing activities of IFITM proteins in SARS-CoV-2 infection.";
RL EMBO J. 40:e106501-e106501(2021).
CC -!- FUNCTION: IFN-induced antiviral protein which disrupts intracellular
CC cholesterol homeostasis. Inhibits the entry of viruses to the host cell
CC cytoplasm by preventing viral fusion with cholesterol depleted
CC endosomes. May inactivate new enveloped viruses which buds out of the
CC infected cell, by letting them go out with a cholesterol depleted
CC membrane. Active against multiple viruses, including influenza A virus,
CC SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV),
CC Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human
CC immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and
CC vesicular stomatitis virus (VSV) (PubMed:26354436, PubMed:33239446,
CC PubMed:33270927). Can inhibit: influenza virus hemagglutinin protein-
CC mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-
CC CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-
CC mediated viral entry (PubMed:33270927). Plays a critical role in the
CC structural stability and function of vacuolar ATPase (v-ATPase).
CC Establishes physical contact with the v-ATPase of endosomes which is
CC critical for proper clathrin localization and is also required for the
CC function of the v-ATPase to lower the pH in phagocytic endosomes thus
CC establishing an antiviral state. In hepatocytes, IFITM proteins act in
CC a coordinated manner to restrict HCV infection by targeting the
CC endocytosed HCV virion for lysosomal degradation (PubMed:26354436).
CC IFITM2 and IFITM3 display anti-HCV activity that may complement the
CC anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry,
CC possibly in a coordinated manner by trapping the virion in the
CC endosomal pathway and targeting it for degradation at the lysosome
CC (PubMed:26354436). Exerts opposing activities on SARS-CoV-2, including
CC amphipathicity-dependent restriction of virus at endosomes and
CC amphipathicity-independent enhancement of infection at the plasma
CC membrane (PubMed:33270927). {ECO:0000269|PubMed:20064371,
CC ECO:0000269|PubMed:20534863, ECO:0000269|PubMed:20943977,
CC ECO:0000269|PubMed:21177806, ECO:0000269|PubMed:21253575,
CC ECO:0000269|PubMed:22046135, ECO:0000269|PubMed:22479637,
CC ECO:0000269|PubMed:23601107, ECO:0000269|PubMed:26354436,
CC ECO:0000269|PubMed:33239446, ECO:0000269|PubMed:33270927}.
CC -!- SUBUNIT: Interacts with ATP6V0B (By similarity). Interacts with CD81
CC (By similarity). Interacts with SPP1; the interaction reduces OPN
CC expression (PubMed:19901966). Interacts with VAPA (PubMed:23601107).
CC Interacts with BRI3 (isoforms 1 and 2); the interaction with isoform 2
CC is weaker than with isoform 1 (PubMed:30983867).
CC {ECO:0000250|UniProtKB:Q9CQW9, ECO:0000269|PubMed:19901966,
CC ECO:0000269|PubMed:23601107, ECO:0000269|PubMed:30983867}.
CC -!- INTERACTION:
CC Q01628; O95870: ABHD16A; NbExp=3; IntAct=EBI-7932862, EBI-348517;
CC Q01628; Q13520: AQP6; NbExp=3; IntAct=EBI-7932862, EBI-13059134;
CC Q01628; O95415: BRI3; NbExp=6; IntAct=EBI-7932862, EBI-2874789;
CC Q01628; P19397: CD53; NbExp=3; IntAct=EBI-7932862, EBI-6657396;
CC Q01628; Q9NXB9: ELOVL2; NbExp=3; IntAct=EBI-7932862, EBI-17206972;
CC Q01628; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-7932862, EBI-781551;
CC Q01628; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-7932862, EBI-18938272;
CC Q01628; O15552: FFAR2; NbExp=3; IntAct=EBI-7932862, EBI-2833872;
CC Q01628; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-7932862, EBI-3918971;
CC Q01628; Q9NZD1: GPRC5D; NbExp=3; IntAct=EBI-7932862, EBI-13067820;
CC Q01628; P43628: KIR2DL3; NbExp=3; IntAct=EBI-7932862, EBI-8632435;
CC Q01628; Q6UWN5: LYPD5; NbExp=3; IntAct=EBI-7932862, EBI-17200970;
CC Q01628; Q96HJ5: MS4A3; NbExp=3; IntAct=EBI-7932862, EBI-12806656;
CC Q01628; P43490: NAMPT; NbExp=3; IntAct=EBI-7932862, EBI-2829310;
CC Q01628; P35372-10: OPRM1; NbExp=3; IntAct=EBI-7932862, EBI-12807478;
CC Q01628; P60201-2: PLP1; NbExp=3; IntAct=EBI-7932862, EBI-12188331;
CC Q01628; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-7932862, EBI-7545592;
CC Q01628; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-7932862, EBI-10192441;
CC Q01628; O95470: SGPL1; NbExp=3; IntAct=EBI-7932862, EBI-1046170;
CC Q01628; Q14973: SLC10A1; NbExp=3; IntAct=EBI-7932862, EBI-3923031;
CC Q01628; Q12908: SLC10A2; NbExp=3; IntAct=EBI-7932862, EBI-18114847;
CC Q01628; O60669: SLC16A7; NbExp=3; IntAct=EBI-7932862, EBI-3921243;
CC Q01628; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-7932862, EBI-8638294;
CC Q01628; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-7932862, EBI-2548832;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20943977,
CC ECO:0000269|PubMed:22511783, ECO:0000269|PubMed:26354436}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:20943977,
CC ECO:0000269|PubMed:22511783}. Late endosome membrane
CC {ECO:0000269|PubMed:22046135}; Single-pass type II membrane protein
CC {ECO:0000305}. Early endosome membrane {ECO:0000269|PubMed:26354436,
CC ECO:0000269|PubMed:33270927}; Single-pass type II membrane protein.
CC Lysosome membrane {ECO:0000269|PubMed:22046135,
CC ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927}; Single-pass
CC type II membrane protein {ECO:0000305}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:30983867}. Note=Co-localizes with BRI3 isoform 1 at
CC the perinuclear region. {ECO:0000269|PubMed:30983867}.
CC -!- INDUCTION: By IFN-alpha and IFNG/IFN-gamma.
CC -!- PTM: Palmitoylation on membrane-proximal cysteines controls clustering
CC in membrane compartments and antiviral activity against influenza virus
CC and hepatitis C virus (HCV). Has no effect on anti-SARS-CoV-2 activity.
CC {ECO:0000269|PubMed:20601941, ECO:0000269|PubMed:22511783,
CC ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927}.
CC -!- PTM: Not glycosylated.
CC -!- PTM: Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages.
CC Ubiquitination negatively regulates antiviral activity. Lys-24 is the
CC most prevalent ubiquitination site. {ECO:0000269|PubMed:22511783}.
CC -!- PTM: Phosphorylation at Tyr-20 is required for endosomal and lysosomal
CC location. {ECO:0000269|PubMed:26354436}.
CC -!- POLYMORPHISM: Genetic variations in IFITM3 are responsible for
CC susceptibility to severe influenza virus infection [MIM:614680].
CC {ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:22446628}.
CC -!- SIMILARITY: Belongs to the CD225/Dispanin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X57352; CAA40626.1; -; mRNA.
DR EMBL; JQ610571; AFF60305.1; -; Genomic_DNA.
DR EMBL; JQ610572; AFF60306.1; -; Genomic_DNA.
DR EMBL; JQ610573; AFF60307.1; -; Genomic_DNA.
DR EMBL; JQ610574; AFF60308.1; -; Genomic_DNA.
DR EMBL; JQ610575; AFF60309.1; -; Genomic_DNA.
DR EMBL; JQ610576; AFF60310.1; -; Genomic_DNA.
DR EMBL; JQ610577; AFF60311.1; -; Genomic_DNA.
DR EMBL; JQ610578; AFF60312.1; -; Genomic_DNA.
DR EMBL; JQ610579; AFF60313.1; -; Genomic_DNA.
DR EMBL; JQ610580; AFF60314.1; -; Genomic_DNA.
DR EMBL; JQ610581; AFF60315.1; -; Genomic_DNA.
DR EMBL; JQ610582; AFF60316.1; -; Genomic_DNA.
DR EMBL; JQ610583; AFF60317.1; -; Genomic_DNA.
DR EMBL; JQ610585; AFF60319.1; -; Genomic_DNA.
DR EMBL; JQ610586; AFF60320.1; -; Genomic_DNA.
DR EMBL; JQ610587; AFF60321.1; -; Genomic_DNA.
DR EMBL; JQ610588; AFF60322.1; -; Genomic_DNA.
DR EMBL; JQ610589; AFF60323.1; -; Genomic_DNA.
DR EMBL; JQ610590; AFF60324.1; -; Genomic_DNA.
DR EMBL; JQ610591; AFF60325.1; -; Genomic_DNA.
DR EMBL; JQ610592; AFF60326.1; -; Genomic_DNA.
DR EMBL; JQ610593; AFF60327.1; -; Genomic_DNA.
DR EMBL; JQ610594; AFF60328.1; -; Genomic_DNA.
DR EMBL; JQ610595; AFF60329.1; -; Genomic_DNA.
DR EMBL; JQ610596; AFF60330.1; -; Genomic_DNA.
DR EMBL; JQ610597; AFF60331.1; -; Genomic_DNA.
DR EMBL; JQ610598; AFF60332.1; -; Genomic_DNA.
DR EMBL; JQ610599; AFF60333.1; -; Genomic_DNA.
DR EMBL; JQ610600; AFF60334.1; -; Genomic_DNA.
DR EMBL; JQ610601; AFF60335.1; -; Genomic_DNA.
DR EMBL; JQ610602; AFF60336.1; -; Genomic_DNA.
DR EMBL; JQ610603; AFF60337.1; -; Genomic_DNA.
DR EMBL; JQ610604; AFF60338.1; -; Genomic_DNA.
DR EMBL; JQ610605; AFF60339.1; -; Genomic_DNA.
DR EMBL; JQ610606; AFF60340.1; -; Genomic_DNA.
DR EMBL; JQ610607; AFF60341.1; -; Genomic_DNA.
DR EMBL; JQ610608; AFF60342.1; -; Genomic_DNA.
DR EMBL; JQ610609; AFF60343.1; -; Genomic_DNA.
DR EMBL; JQ610610; AFF60344.1; -; Genomic_DNA.
DR EMBL; JQ610611; AFF60345.1; -; Genomic_DNA.
DR EMBL; JQ610613; AFF60347.1; -; Genomic_DNA.
DR EMBL; JQ610614; AFF60348.1; -; Genomic_DNA.
DR EMBL; JQ610615; AFF60349.1; -; Genomic_DNA.
DR EMBL; JQ610616; AFF60350.1; -; Genomic_DNA.
DR EMBL; JQ610617; AFF60351.1; -; Genomic_DNA.
DR EMBL; JQ610618; AFF60352.1; -; Genomic_DNA.
DR EMBL; JQ610620; AFF60354.1; -; Genomic_DNA.
DR EMBL; JQ610621; AFF60355.1; -; Genomic_DNA.
DR EMBL; BT006892; AAP35538.1; -; mRNA.
DR EMBL; AK292173; BAF84862.1; -; mRNA.
DR EMBL; AC136475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH891444; EAW50866.1; -; Genomic_DNA.
DR EMBL; BC006794; AAH06794.1; -; mRNA.
DR EMBL; BC008417; AAH08417.1; -; mRNA.
DR EMBL; BC022439; AAH22439.1; -; mRNA.
DR EMBL; BC070243; AAH70243.1; -; mRNA.
DR CCDS; CCDS41585.1; -.
DR PIR; S17182; S17182.
DR RefSeq; NP_066362.2; NM_021034.2.
DR AlphaFoldDB; Q01628; -.
DR BioGRID; 115681; 561.
DR IntAct; Q01628; 30.
DR MINT; Q01628; -.
DR STRING; 9606.ENSP00000382707; -.
DR TCDB; 8.A.58.1.3; the dispanin (dispanin) family.
DR GlyGen; Q01628; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q01628; -.
DR PhosphoSitePlus; Q01628; -.
DR SwissPalm; Q01628; -.
DR BioMuta; IFITM3; -.
DR DMDM; 20178301; -.
DR jPOST; Q01628; -.
DR MassIVE; Q01628; -.
DR PaxDb; 9606-ENSP00000382707; -.
DR PeptideAtlas; Q01628; -.
DR ProteomicsDB; 57973; -.
DR Pumba; Q01628; -.
DR TopDownProteomics; Q01628; -.
DR Antibodypedia; 1023; 383 antibodies from 38 providers.
DR DNASU; 10410; -.
DR Ensembl; ENST00000399808.5; ENSP00000382707.4; ENSG00000142089.17.
DR GeneID; 10410; -.
DR KEGG; hsa:10410; -.
DR MANE-Select; ENST00000399808.5; ENSP00000382707.4; NM_021034.3; NP_066362.2.
DR UCSC; uc001lpa.3; human.
DR AGR; HGNC:5414; -.
DR CTD; 10410; -.
DR DisGeNET; 10410; -.
DR GeneCards; IFITM3; -.
DR HGNC; HGNC:5414; IFITM3.
DR HPA; ENSG00000142089; Low tissue specificity.
DR MalaCards; IFITM3; -.
DR MIM; 605579; gene.
DR MIM; 614680; phenotype.
DR neXtProt; NX_Q01628; -.
DR OpenTargets; ENSG00000142089; -.
DR PharmGKB; PA29655; -.
DR VEuPathDB; HostDB:ENSG00000142089; -.
DR eggNOG; ENOG502S9XK; Eukaryota.
DR GeneTree; ENSGT00950000182857; -.
DR InParanoid; Q01628; -.
DR OMA; HIVWSIC; -.
DR OrthoDB; 5322528at2759; -.
DR PhylomeDB; Q01628; -.
DR TreeFam; TF334894; -.
DR PathwayCommons; Q01628; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; Q01628; -.
DR SIGNOR; Q01628; -.
DR BioGRID-ORCS; 10410; 660 hits in 1125 CRISPR screens.
DR ChiTaRS; IFITM3; human.
DR GeneWiki; IFITM3; -.
DR GenomeRNAi; 10410; -.
DR Pharos; Q01628; Tbio.
DR PRO; PR:Q01628; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q01628; Protein.
DR Bgee; ENSG00000142089; Expressed in left uterine tube and 206 other cell types or tissues.
DR ExpressionAtlas; Q01628; baseline and differential.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0032897; P:negative regulation of viral transcription; IDA:UniProtKB.
DR GO; GO:0035455; P:response to interferon-alpha; IDA:UniProtKB.
DR GO; GO:0035456; P:response to interferon-beta; IDA:UniProtKB.
DR GO; GO:0034341; P:response to type II interferon; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IBA:GO_Central.
DR InterPro; IPR007593; CD225/Dispanin_fam.
DR InterPro; IPR051517; IFITM_antiviral_protein.
DR PANTHER; PTHR13999; INTERFERON INDUCIBLE TRANSMEMBRANE PROTEIN; 1.
DR PANTHER; PTHR13999:SF4; INTERFERON-INDUCED TRANSMEMBRANE PROTEIN 3; 1.
DR Pfam; PF04505; CD225; 1.
PE 1: Evidence at protein level;
KW Antiviral defense; Cell membrane; Cytoplasm; Endosome; Immunity;
KW Innate immunity; Isopeptide bond; Lipoprotein; Lysosome; Membrane;
KW Palmitate; Phosphoprotein; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..133
FT /note="Interferon-induced transmembrane protein 3"
FT /id="PRO_0000153729"
FT TOPO_DOM 1..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 129..133
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 60..93
FT /note="Interaction with SPP1"
FT /evidence="ECO:0000269|PubMed:19901966"
FT REGION 108..133
FT /note="Interaction with VAPA"
FT /evidence="ECO:0000269|PubMed:23601107"
FT MOD_RES 20
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26354436"
FT LIPID 71
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:20601941"
FT LIPID 72
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:20601941"
FT LIPID 105
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:20601941"
FT CROSSLNK 24
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22511783"
FT CROSSLNK 83
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22511783"
FT CROSSLNK 88
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22511783"
FT CROSSLNK 104
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22511783"
FT VARIANT 3
FT /note="H -> Q (in dbSNP:rs1136853)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_053810"
FT MUTAGEN 20
FT /note="Y->A: Loss of phosphorylation. Accumulates at the
FT plasma membrane. Increases anti-HCV properties. Loss of
FT anti-SARS-CoV-2 activity by enhancing Spike-mediated cell-
FT to-cell fusion."
FT /evidence="ECO:0000269|PubMed:26354436,
FT ECO:0000269|PubMed:33270927"
FT MUTAGEN 23
FT /note="L->Q: Accumulates at the plasma membrane. Loss of
FT anti-SARS-CoV-2 activity by enhancing Spike-mediated cell-
FT to-cell fusion."
FT /evidence="ECO:0000269|PubMed:33270927"
FT MUTAGEN 59..68
FT /note="Missing: Slightly enhances infection by SARS-CoV-2."
FT /evidence="ECO:0000269|PubMed:33270927"
FT MUTAGEN 61..65
FT /note="SLFNT->ALFAA: Decreases anti-SARS-CoV-2 activity."
FT /evidence="ECO:0000269|PubMed:33270927"
FT MUTAGEN 71..72
FT /note="CC->AA: Loss of anti-HCV activity. Only localizes at
FT the lysosome. No effect on SARS-CoV-2 infection; when
FT associated with A-105. Loss of anti-influenza A virus
FT activity; when associated with A-105."
FT /evidence="ECO:0000269|PubMed:26354436,
FT ECO:0000269|PubMed:33270927"
FT MUTAGEN 105
FT /note="C->A: Loss of anti-HCV activity. Only localizes at
FT the lysosome. No effect on SARS-CoV-2 infection; when
FT associated with 71-A-A-72. Loss of anti-influenza A virus
FT activity; when associated with 71-A-A-72."
FT /evidence="ECO:0000269|PubMed:26354436,
FT ECO:0000269|PubMed:33270927"
FT CONFLICT 2
FT /note="N -> S (in Ref. 1; CAA40626)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="A -> G (in Ref. 1; CAA40626)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 133 AA; 14632 MW; 9FFB2E4623F7A1DD CRC64;
MNHTVQTFFS PVNSGQPPNY EMLKEEHEVA VLGAPHNPAP PTSTVIHIRS ETSVPDHVVW
SLFNTLFMNP CCLGFIAFAY SVKSRDRKMV GDVTGAQAYA STAKCLNIWA LILGILMTIL
LIVIPVLIFQ AYG
//