ID IFM2_HUMAN Reviewed; 132 AA.
AC Q01629; Q6FH82; Q96DA8;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 02-OCT-2024, entry version 175.
DE RecName: Full=Interferon-induced transmembrane protein 2 {ECO:0000305};
DE AltName: Full=Dispanin subfamily A member 2c;
DE Short=DSPA2c;
DE AltName: Full=Interferon-inducible protein 1-8D;
GN Name=IFITM2 {ECO:0000312|HGNC:HGNC:5413};
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], AND VARIANTS THR-41 AND VAL-121.
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 [LARGE SCALE MRNA], AND VARIANT ALA-33.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-33; THR-41 AND
RP VAL-121.
RC TISSUE=Lung;
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 [5]
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 [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=19544527; DOI=10.1002/ijc.24669;
RA Daniel-Carmi V., Makovitzki-Avraham E., Reuven E.M., Goldstein I.,
RA Zilkha N., Rotter V., Tzehoval E., Eisenbach L.;
RT "The human 1-8D gene (IFITM2) is a novel p53 independent pro-apoptotic
RT gene.";
RL Int. J. Cancer 125:2810-2819(2009).
RN [7]
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 [8]
RP FUNCTION.
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-19, PALMITOYLATION
RP AT CYS-70; CYS-71 AND CYS-104, INTERACTION WITH CD81, AND MUTAGENESIS OF
RP TYR-19; 70-CYS-CYS-71 AND CYS-104.
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 [18]
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 [19]
RP FUNCTION.
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).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-19, AND INDUCTION BY
RP IFNB1.
RX PubMed=33563656; DOI=10.1128/jvi.02422-20;
RA Winstone H., Lista M.J., Reid A.C., Bouton C., Pickering S., Galao R.P.,
RA Kerridge C., Doores K.J., Swanson C., Neil S.;
RT "The polybasic cleavage site in the SARS-CoV-2 spike modulates viral
RT sensitivity to Type I interferon and IFITM2.";
RL J. Virol. 0:0-0(2021).
CC -!- FUNCTION: IFN-induced antiviral protein which inhibits the entry of
CC viruses to the host cell cytoplasm, permitting endocytosis, but
CC preventing subsequent viral fusion and release of viral contents into
CC the cytosol (PubMed:26354436, PubMed:33563656). Active against multiple
CC viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and
CC SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus
CC (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-
CC 1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV)
CC (PubMed:26354436, PubMed:33239446, PubMed:33270927, PubMed:33563656).
CC Can inhibit: influenza virus hemagglutinin protein-mediated viral
CC entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-
CC 2 S protein-mediated viral entry and VSV G protein-mediated viral entry
CC (PubMed:33563656). Induces cell cycle arrest and mediates apoptosis by
CC caspase activation and in p53-independent manner. In hepatocytes, IFITM
CC proteins act in a coordinated manner to restrict HCV infection by
CC targeting the endocytosed HCV virion for lysosomal degradation
CC (PubMed:26354436). IFITM2 and IFITM3 display anti-HCV activity that may
CC complement the anti-HCV activity of IFITM1 by inhibiting the late
CC stages of HCV entry, possibly in a coordinated manner by trapping the
CC virion in the endosomal pathway and targeting it for degradation at the
CC lysosome (PubMed:26354436). {ECO:0000269|PubMed:19544527,
CC ECO:0000269|PubMed:20064371, ECO:0000269|PubMed:20534863,
CC ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:21177806,
CC ECO:0000269|PubMed:21253575, ECO:0000269|PubMed:22479637,
CC ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33239446,
CC ECO:0000269|PubMed:33270927, ECO:0000269|PubMed:33563656}.
CC -!- SUBUNIT: Interacts with CD81. {ECO:0000250|UniProtKB:Q99J93}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:33563656};
CC Single-pass type II membrane protein {ECO:0000305}. Lysosome membrane
CC {ECO:0000269|PubMed:26354436}; Single-pass type II membrane protein
CC {ECO:0000305}. Late endosome membrane {ECO:0000269|PubMed:26354436};
CC Single-pass type II membrane protein {ECO:0000305}.
CC -!- INDUCTION: By IFN-alpha, IFNB1/IFN-beta and IFNG/IFN-gamma. Down-
CC regulated by p53/TP53. {ECO:0000269|PubMed:19544527,
CC ECO:0000269|PubMed:33563656}.
CC -!- PTM: Palmitoylation on membrane-proximal cysteines controls clustering
CC in membrane compartments and antiviral activity.
CC {ECO:0000305|PubMed:26354436}.
CC -!- PTM: Phosphorylation at Tyr-19 is required for endosomal and lysosomal
CC location. {ECO:0000269|PubMed:26354436}.
CC -!- SIMILARITY: Belongs to the CD225/Dispanin family. {ECO:0000305}.
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DR EMBL; X57351; CAA40625.1; -; mRNA.
DR EMBL; CR541874; CAG46672.1; -; mRNA.
DR EMBL; AC136475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009696; AAH09696.1; -; mRNA.
DR CCDS; CCDS41583.1; -.
DR PIR; S17183; S17183.
DR RefSeq; NP_006426.2; NM_006435.2.
DR AlphaFoldDB; Q01629; -.
DR SMR; Q01629; -.
DR BioGRID; 115832; 8.
DR IntAct; Q01629; 6.
DR STRING; 9606.ENSP00000484689; -.
DR TCDB; 8.A.58.1.2; the dispanin (dispanin) family.
DR iPTMnet; Q01629; -.
DR PhosphoSitePlus; Q01629; -.
DR SwissPalm; Q01629; -.
DR BioMuta; IFITM2; -.
DR DMDM; 290457648; -.
DR jPOST; Q01629; -.
DR MassIVE; Q01629; -.
DR PaxDb; 9606-ENSP00000484689; -.
DR PeptideAtlas; Q01629; -.
DR ProteomicsDB; 57974; -.
DR Pumba; Q01629; -.
DR Antibodypedia; 22433; 316 antibodies from 25 providers.
DR DNASU; 10581; -.
DR Ensembl; ENST00000616316.3; ENSP00000484689.1; ENSG00000185201.18.
DR Ensembl; ENST00000680197.1; ENSP00000505840.1; ENSG00000185201.18.
DR GeneID; 10581; -.
DR KEGG; hsa:10581; -.
DR MANE-Select; ENST00000616316.3; ENSP00000484689.1; NM_006435.3; NP_006426.2.
DR UCSC; uc001lox.5; human.
DR AGR; HGNC:5413; -.
DR CTD; 10581; -.
DR DisGeNET; 10581; -.
DR GeneCards; IFITM2; -.
DR HGNC; HGNC:5413; IFITM2.
DR HPA; ENSG00000185201; Low tissue specificity.
DR MIM; 605578; gene.
DR neXtProt; NX_Q01629; -.
DR OpenTargets; ENSG00000185201; -.
DR PharmGKB; PA29654; -.
DR VEuPathDB; HostDB:ENSG00000185201; -.
DR eggNOG; ENOG502S9XK; Eukaryota.
DR GeneTree; ENSGT00950000182857; -.
DR InParanoid; Q01629; -.
DR OMA; AKFLNIC; -.
DR OrthoDB; 5322528at2759; -.
DR PhylomeDB; Q01629; -.
DR TreeFam; TF334894; -.
DR PathwayCommons; Q01629; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; Q01629; -.
DR BioGRID-ORCS; 10581; 329 hits in 1120 CRISPR screens.
DR ChiTaRS; IFITM2; human.
DR GenomeRNAi; 10581; -.
DR Pharos; Q01629; Tbio.
DR PRO; PR:Q01629; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q01629; protein.
DR Bgee; ENSG00000185201; Expressed in blood and 210 other cell types or tissues.
DR ExpressionAtlas; Q01629; baseline and differential.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central.
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: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:SF8; INTERFERON-INDUCED TRANSMEMBRANE PROTEIN 2; 1.
DR Pfam; PF04505; CD225; 1.
PE 1: Evidence at protein level;
KW Acetylation; Antiviral defense; Cell membrane; Endosome; Immunity;
KW Innate immunity; Lipoprotein; Lysosome; Membrane; Palmitate;
KW Phosphoprotein; Proteomics identification; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..132
FT /note="Interferon-induced transmembrane protein 2"
FT /id="PRO_0000153728"
FT TOPO_DOM 1..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P13164"
FT TOPO_DOM 78..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..132
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 19
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26354436"
FT LIPID 70
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:26354436"
FT LIPID 71
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:26354436"
FT LIPID 104
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:26354436"
FT VARIANT 33
FT /note="V -> A (in dbSNP:rs1058900)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_062677"
FT VARIANT 41
FT /note="M -> T (in dbSNP:rs14408)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1906403"
FT /id="VAR_014848"
FT VARIANT 121
FT /note="I -> V (in dbSNP:rs1059091)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1906403"
FT /id="VAR_060470"
FT MUTAGEN 19
FT /note="Y->F,A: Loss of phosphorylation. Accumulates at the
FT plasma membrane. Increases infection with influenza A virus
FT and SARS-CoV-2. Increases anti-HCV properties."
FT /evidence="ECO:0000269|PubMed:26354436,
FT ECO:0000269|PubMed:33563656"
FT MUTAGEN 70..71
FT /note="CC->AA: No effect on anti-HCV activity. Partial loss
FT of endosomal location."
FT /evidence="ECO:0000269|PubMed:26354436"
FT MUTAGEN 104
FT /note="C->A: Loss of anti-HCV activity. Partial loss of
FT endosomal location."
FT /evidence="ECO:0000269|PubMed:26354436"
FT CONFLICT 33
FT /note="V -> G (in Ref. 1; CAA40625)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 132 AA; 14632 MW; 232A32D109EEBF5D CRC64;
MNHIVQTFSP VNSGQPPNYE MLKEEQEVAM LGVPHNPAPP MSTVIHIRSE TSVPDHVVWS
LFNTLFMNTC CLGFIAFAYS VKSRDRKMVG DVTGAQAYAS TAKCLNIWAL ILGIFMTILL
IIIPVLVVQA QR
//