ID IFIT3_HUMAN Reviewed; 490 AA.
AC O14879; Q99634; Q9BSK7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 24-JAN-2024, entry version 199.
DE RecName: Full=Interferon-induced protein with tetratricopeptide repeats 3;
DE Short=IFIT-3;
DE AltName: Full=CIG49;
DE AltName: Full=ISG-60;
DE AltName: Full=Interferon-induced 60 kDa protein;
DE Short=IFI-60K;
DE AltName: Full=Interferon-induced protein with tetratricopeptide repeats 4;
DE Short=IFIT-4;
DE AltName: Full=Retinoic acid-induced gene G protein;
DE Short=P60;
DE Short=RIG-G;
GN Name=IFIT3; Synonyms=CIG-49, IFI60, IFIT4, ISG60;
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].
RC TISSUE=Foreskin;
RX PubMed=9391139; DOI=10.1073/pnas.94.25.13985;
RA Zhu H., Cong J.-P., Shenk T.;
RT "Use of differential display analysis to assess the effect of human
RT cytomegalovirus infection on the accumulation of cellular RNAs: induction
RT of interferon-responsive RNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9828129; DOI=10.1006/geno.1998.5555;
RA de Veer M.J., Sim H., Whisstock J.C., Devenish R.J., Ralph S.J.;
RT "IFI60/ISG60/IFIT4, a new member of the human IFI54/IFIT2 family of
RT interferon-stimulated genes.";
RL Genomics 54:267-277(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yu M., Tong J., Mao M., Chen S., Chen Z.;
RT "RIG-G, a novel gene induced by ATRA in acute promyelocytic leukemia cells,
RT is a new member of the ISG family.";
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [6]
RP FUNCTION, INDUCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH COPS5.
RX PubMed=17050680; DOI=10.1073/pnas.0607830103;
RA Xiao S., Li D., Zhu H.Q., Song M.G., Pan X.R., Jia P.M., Peng L.L.,
RA Dou A.X., Chen G.Q., Chen S.J., Chen Z., Tong J.H.;
RT "RIG-G as a key mediator of the antiproliferative activity of interferon-
RT related pathways through enhancing p21 and p27 proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18706081; DOI=10.1186/ar2475;
RA Huang X., Shen N., Bao C., Gu Y., Wu L., Chen S.;
RT "Interferon-induced protein IFIT4 is associated with systemic lupus
RT erythematosus and promotes differentiation of monocytes into dendritic
RT cell-like cells.";
RL Arthritis Res. Ther. 10:R91-R91(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-237, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-478, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION.
RX PubMed=20686046; DOI=10.1128/jvi.00818-10;
RA Schmeisser H., Mejido J., Balinsky C.A., Morrow A.N., Clark C.R., Zhao T.,
RA Zoon K.C.;
RT "Identification of alpha interferon-induced genes associated with antiviral
RT activity in Daudi cells and characterization of IFIT3 as a novel antiviral
RT gene.";
RL J. Virol. 84:10671-10680(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND IDENTIFICATION BY
RP MASS 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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP FUNCTION, AND INTERACTION WITH IFIT2.
RX PubMed=21190939; DOI=10.1074/jbc.m110.207068;
RA Stawowczyk M., Van Scoy S., Kumar K.P., Reich N.C.;
RT "The interferon stimulated gene 54 promotes apoptosis.";
RL J. Biol. Chem. 286:7257-7266(2011).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAVS; TBK1; TRAF6 AND
RP RIGI.
RX PubMed=21813773; DOI=10.4049/jimmunol.1100963;
RA Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.;
RT "IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging
RT MAVS and TBK1.";
RL J. Immunol. 187:2559-2568(2011).
RN [15]
RP REVIEW.
RX PubMed=20950130; DOI=10.1089/jir.2010.0101;
RA Fensterl V., Sen G.C.;
RT "The ISG56/IFIT1 gene family.";
RL J. Interferon Cytokine Res. 31:71-78(2011).
RN [16]
RP FUNCTION, AND INTERACTION WITH IFIT1 AND IFIT2.
RX PubMed=21642987; DOI=10.1038/ni.2048;
RA Pichlmair A., Lassnig C., Eberle C.A., Gorna M.W., Baumann C.L.,
RA Burkard T.R., Buerckstuemmer T., Stefanovic A., Krieger S., Bennett K.L.,
RA Ruelicke T., Weber F., Colinge J., Mueller M., Superti-Furga G.;
RT "IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA.";
RL Nat. Immunol. 12:624-630(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-478, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: IFN-induced antiviral protein which acts as an inhibitor of
CC cellular as well as viral processes, cell migration, proliferation,
CC signaling, and viral replication. Enhances MAVS-mediated host antiviral
CC responses by serving as an adapter bridging TBK1 to MAVS which leads to
CC the activation of TBK1 and phosphorylation of IRF3 and phosphorylated
CC IRF3 translocates into nucleus to promote antiviral gene transcription.
CC Exhibits an antiproliferative activity via the up-regulation of cell
CC cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally,
CC CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in
CC the nucleus and exports it to the cytoplasm for ubiquitin-dependent
CC degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby
CC increasing nuclear CDKN1B/p27 protein levels. Up-regulates CDKN1A/p21
CC by down-regulating MYC, a repressor of CDKN1A/p21. Can negatively
CC regulate the apoptotic effects of IFIT2. {ECO:0000269|PubMed:17050680,
CC ECO:0000269|PubMed:20686046, ECO:0000269|PubMed:21190939,
CC ECO:0000269|PubMed:21642987, ECO:0000269|PubMed:21813773}.
CC -!- SUBUNIT: Component of an interferon-dependent multiprotein complex, at
CC least composed of IFIT1, IFIT2 and IFIT3 (PubMed:21642987). Interacts
CC with IFIT1 and IFIT2 (PubMed:21190939, PubMed:21642987). Interacts (via
CC N-terminus) with MAVS, TBK1, TRAF6 and RIGI (PubMed:21813773).
CC Interacts with COPS5 (PubMed:17050680). {ECO:0000269|PubMed:17050680,
CC ECO:0000269|PubMed:21190939, ECO:0000269|PubMed:21642987,
CC ECO:0000269|PubMed:21813773}.
CC -!- INTERACTION:
CC O14879; Q16543: CDC37; NbExp=4; IntAct=EBI-745127, EBI-295634;
CC O14879; Q92905: COPS5; NbExp=4; IntAct=EBI-745127, EBI-594661;
CC O14879; Q05D60: DEUP1; NbExp=4; IntAct=EBI-745127, EBI-748597;
CC O14879; Q0P5U8: FLJ90650; NbExp=3; IntAct=EBI-745127, EBI-10226698;
CC O14879; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-745127, EBI-2514791;
CC O14879; P09914: IFIT1; NbExp=12; IntAct=EBI-745127, EBI-745117;
CC O14879; Q5T764: IFIT1B; NbExp=6; IntAct=EBI-745127, EBI-3507164;
CC O14879; P09913: IFIT2; NbExp=6; IntAct=EBI-745127, EBI-3507167;
CC O14879; Q8IZ03: IFIT2; NbExp=4; IntAct=EBI-745127, EBI-746217;
CC O14879; O14879: IFIT3; NbExp=3; IntAct=EBI-745127, EBI-745127;
CC O14879; Q8IXX5: TMEM183A; NbExp=7; IntAct=EBI-745127, EBI-2841953;
CC O14879; P09493-10: TPM1; NbExp=4; IntAct=EBI-745127, EBI-12123928;
CC O14879; P06753: TPM3; NbExp=5; IntAct=EBI-745127, EBI-355607;
CC O14879; Q5VU62: TPM3; NbExp=3; IntAct=EBI-745127, EBI-10184033;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17050680,
CC ECO:0000269|PubMed:18706081}. Mitochondrion
CC {ECO:0000269|PubMed:21813773}.
CC -!- TISSUE SPECIFICITY: Expression significantly higher in peripheral blood
CC mononuclear cells (PBMCs) and monocytes from systemic lupus
CC erythematosus (SLE) patients than in those from healthy individuals (at
CC protein level). Spleen, lung, leukocytes, lymph nodes, placenta, bone
CC marrow and fetal liver. {ECO:0000269|PubMed:18706081}.
CC -!- INDUCTION: By type I interferons, dsRNAs and viruses.
CC {ECO:0000269|PubMed:17050680}.
CC -!- SIMILARITY: Belongs to the IFIT family. {ECO:0000305}.
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DR EMBL; AF026939; AAB95160.1; -; mRNA.
DR EMBL; AF083470; AAC63524.1; -; mRNA.
DR EMBL; U52513; AAB40606.1; -; mRNA.
DR EMBL; BT007284; AAP35948.1; -; mRNA.
DR EMBL; BC001383; AAH01383.1; -; mRNA.
DR EMBL; BC004977; AAH04977.1; -; mRNA.
DR CCDS; CCDS31241.1; -.
DR CCDS; CCDS7402.1; -.
DR RefSeq; NP_001026853.1; NM_001031683.3.
DR RefSeq; NP_001540.2; NM_001549.5.
DR PDB; 6C6K; X-ray; 2.54 A; C/D=416-459.
DR PDBsum; 6C6K; -.
DR AlphaFoldDB; O14879; -.
DR SMR; O14879; -.
DR BioGRID; 109660; 81.
DR DIP; DIP-37890N; -.
DR IntAct; O14879; 66.
DR MINT; O14879; -.
DR STRING; 9606.ENSP00000360876; -.
DR GlyCosmos; O14879; 2 sites, 1 glycan.
DR GlyGen; O14879; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O14879; -.
DR PhosphoSitePlus; O14879; -.
DR BioMuta; IFIT3; -.
DR EPD; O14879; -.
DR jPOST; O14879; -.
DR MassIVE; O14879; -.
DR PaxDb; 9606-ENSP00000360883; -.
DR PeptideAtlas; O14879; -.
DR ProteomicsDB; 48279; -.
DR Pumba; O14879; -.
DR Antibodypedia; 30262; 308 antibodies from 31 providers.
DR CPTC; O14879; 1 antibody.
DR DNASU; 3437; -.
DR Ensembl; ENST00000371811.4; ENSP00000360876.4; ENSG00000119917.15.
DR Ensembl; ENST00000371818.9; ENSP00000360883.4; ENSG00000119917.15.
DR Ensembl; ENST00000679781.1; ENSP00000505987.1; ENSG00000119917.15.
DR GeneID; 3437; -.
DR KEGG; hsa:3437; -.
DR MANE-Select; ENST00000371818.9; ENSP00000360883.4; NM_001549.6; NP_001540.2.
DR AGR; HGNC:5411; -.
DR CTD; 3437; -.
DR DisGeNET; 3437; -.
DR GeneCards; IFIT3; -.
DR HGNC; HGNC:5411; IFIT3.
DR HPA; ENSG00000119917; Low tissue specificity.
DR MIM; 604650; gene.
DR neXtProt; NX_O14879; -.
DR OpenTargets; ENSG00000119917; -.
DR PharmGKB; PA29651; -.
DR VEuPathDB; HostDB:ENSG00000119917; -.
DR eggNOG; KOG1124; Eukaryota.
DR GeneTree; ENSGT00950000182946; -.
DR HOGENOM; CLU_043482_0_0_1; -.
DR InParanoid; O14879; -.
DR OMA; NPYSIES; -.
DR OrthoDB; 5401272at2759; -.
DR PhylomeDB; O14879; -.
DR TreeFam; TF342671; -.
DR PathwayCommons; O14879; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; O14879; -.
DR BioGRID-ORCS; 3437; 10 hits in 1152 CRISPR screens.
DR ChiTaRS; IFIT3; human.
DR GeneWiki; IFIT3; -.
DR GenomeRNAi; 3437; -.
DR Pharos; O14879; Tbio.
DR PRO; PR:O14879; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O14879; Protein.
DR Bgee; ENSG00000119917; Expressed in trigeminal ganglion and 194 other cell types or tissues.
DR ExpressionAtlas; O14879; baseline and differential.
DR Genevisible; O14879; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt.
DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 3.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10271; INTERFERON-INDUCED PROTEIN WITH TETRATRICOPEPTIDE REPEATS; 1.
DR PANTHER; PTHR10271:SF3; INTERFERON-INDUCED PROTEIN WITH TETRATRICOPEPTIDE REPEATS 3; 1.
DR Pfam; PF13424; TPR_12; 1.
DR Pfam; PF13176; TPR_7; 1.
DR Pfam; PF13181; TPR_8; 2.
DR SMART; SM00028; TPR; 5.
DR SUPFAM; SSF48452; TPR-like; 2.
DR PROSITE; PS50005; TPR; 5.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Cytoplasm; Immunity; Innate immunity;
KW Mitochondrion; Phosphoprotein; Reference proteome; Repeat; TPR repeat.
FT CHAIN 1..490
FT /note="Interferon-induced protein with tetratricopeptide
FT repeats 3"
FT /id="PRO_0000106349"
FT REPEAT 51..84
FT /note="TPR 1"
FT REPEAT 94..127
FT /note="TPR 2"
FT REPEAT 136..169
FT /note="TPR 3"
FT REPEAT 172..206
FT /note="TPR 4"
FT REPEAT 207..240
FT /note="TPR 5"
FT REPEAT 241..274
FT /note="TPR 6"
FT REPEAT 415..448
FT /note="TPR 7"
FT REPEAT 450..481
FT /note="TPR 8"
FT REGION 467..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 471..490
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT CONFLICT 44
FT /note="F -> S (in Ref. 5; AAH04977)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="Q -> QQ (in Ref. 2; AAB40606)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="Missing (in Ref. 2; AAB40606)"
FT /evidence="ECO:0000305"
FT HELIX 417..428
FT /evidence="ECO:0007829|PDB:6C6K"
FT HELIX 431..445
FT /evidence="ECO:0007829|PDB:6C6K"
FT TURN 446..448
FT /evidence="ECO:0007829|PDB:6C6K"
FT HELIX 453..457
FT /evidence="ECO:0007829|PDB:6C6K"
SQ SEQUENCE 490 AA; 55985 MW; B9F042D4DF7151D2 CRC64;
MSEVTKNSLE KILPQLKCHF TWNLFKEDSV SRDLEDRVCN QIEFLNTEFK ATMYNLLAYI
KHLDGNNEAA LECLRQAEEL IQQEHADQAE IRSLVTWGNY AWVYYHLGRL SDAQIYVDKV
KQTCKKFSNP YSIEYSELDC EEGWTQLKCG RNERAKVCFE KALEEKPNNP EFSSGLAIAM
YHLDNHPEKQ FSTDVLKQAI ELSPDNQYVK VLLGLKLQKM NKEAEGEQFV EEALEKSPCQ
TDVLRSAAKF YRRKGDLDKA IELFQRVLES TPNNGYLYHQ IGCCYKAKVR QMQNTGESEA
SGNKEMIEAL KQYAMDYSNK ALEKGLNPLN AYSDLAEFLE TECYQTPFNK EVPDAEKQQS
HQRYCNLQKY NGKSEDTAVQ HGLEGLSISK KSTDKEEIKD QPQNVSENLL PQNAPNYWYL
QGLIHKQNGD LLQAAKCYEK ELGRLLRDAP SGIGSIFLSA SELEDGSEEM GQGAVSSSPR
ELLSNSEQLN
//
