IFIT2_HUMAN
ID IFIT2_HUMAN Reviewed; 472 AA.
AC P09913; Q5T767;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Interferon-induced protein with tetratricopeptide repeats 2;
DE Short=IFIT-2;
DE AltName: Full=ISG-54 K;
DE AltName: Full=Interferon-induced 54 kDa protein;
DE Short=IFI-54K;
DE Short=P54;
GN Name=IFIT2; Synonyms=CIG-42, G10P2, IFI54, ISG54;
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 [GENOMIC DNA].
RX PubMed=3466167; DOI=10.1073/pnas.83.23.8929;
RA Levy D., Larner A., Chaudhuri A., Babiss L.E., Darnell J.E. Jr.;
RT "Interferon-stimulated transcription: isolation of an inducible gene and
RT identification of its regulatory region.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8929-8933(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2.
RX PubMed=2454816; DOI=10.1111/j.1432-1033.1988.tb14101.x;
RA Wathelet M.G., Clauss I.M., Content J., Huez G.A.;
RT "Regulation of two interferon-inducible human genes by interferon,
RT poly(rI).poly(rC) and viruses.";
RL Eur. J. Biochem. 174:323-329(1988).
RN [4]
RP SIMILARITY TO IFI-56K.
RX PubMed=3360121; DOI=10.1016/0014-5793(88)80724-5;
RA Wathelet M.G., Clauss I.M., Content J., Huez G.A.;
RT "The IFI-56K and IFI-54K interferon-inducible human genes belong to the
RT same gene family.";
RL FEBS Lett. 231:164-171(1988).
RN [5]
RP INDUCTION, AND INTERACTION WITH EIF3E AND EIF3C.
RX PubMed=16973618; DOI=10.1074/jbc.m605771200;
RA Terenzi F., Hui D.J., Merrick W.C., Sen G.C.;
RT "Distinct induction patterns and functions of two closely related
RT interferon-inducible human genes, ISG54 and ISG56.";
RL J. Biol. Chem. 281:34064-34071(2006).
RN [6]
RP INTERACTION WITH STING1/MITA.
RX PubMed=19416887; DOI=10.1073/pnas.0900818106;
RA Li Y., Li C., Xue P., Zhong B., Mao A.P., Ran Y., Chen H., Wang Y.Y.,
RA Yang F., Shu H.B.;
RT "ISG56 is a negative-feedback regulator of virus-triggered signaling and
RT cellular antiviral response.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:7945-7950(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IFIT1 AND IFIT3.
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 [8]
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 [9]
RP INTERACTION WITH IFIT1 AND IFIT3.
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), TPR REPEATS, SUBUNIT, AND
RP MUTAGENESIS OF ARG-184; LYS-255; ARG-259; ARG-292 AND LYS-410.
RX PubMed=22825553; DOI=10.1038/cr.2012.111;
RA Yang Z., Liang H., Zhou Q., Li Y., Chen H., Ye W., Chen D., Fleming J.,
RA Shu H., Liu Y.;
RT "Crystal structure of ISG54 reveals a novel RNA binding structure and
RT potential functional mechanisms.";
RL Cell Res. 22:1328-1338(2012).
CC -!- FUNCTION: IFN-induced antiviral protein which inhibits expression of
CC viral messenger RNAs lacking 2'-O-methylation of the 5' cap. The ribose
CC 2'-O-methylation would provide a molecular signature to distinguish
CC between self and non-self mRNAs by the host during viral infection.
CC Viruses evolved several ways to evade this restriction system such as
CC encoding their own 2'-O-methylase for their mRNAs or by stealing host
CC cap containing the 2'-O-methylation (cap snatching mechanism). Binds
CC AU-rich viral RNAs, with or without 5' triphosphorylation, RNA-binding
CC is required for antiviral activity. Can promote apoptosis.
CC {ECO:0000269|PubMed:21190939}.
CC -!- SUBUNIT: Domain-swapped homodimer. Component of an interferon-dependent
CC multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3.
CC Interacts with IFIT1 and IFIT3. Interacts with STING1/MITA and disrupts
CC its interaction with MAVS or TBK1. Interacts with EIF3E and EIF3C.
CC {ECO:0000269|PubMed:16973618, ECO:0000269|PubMed:19416887,
CC ECO:0000269|PubMed:21190939, ECO:0000269|PubMed:21642987,
CC ECO:0000269|PubMed:22825553}.
CC -!- INTERACTION:
CC P09913; P09914: IFIT1; NbExp=6; IntAct=EBI-3507167, EBI-745117;
CC P09913; O14879: IFIT3; NbExp=6; IntAct=EBI-3507167, EBI-745127;
CC P09913; Q86WV6: STING1; NbExp=3; IntAct=EBI-3507167, EBI-2800345;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21190939}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:21190939}.
CC -!- INDUCTION: By type I interferons, dsRNAs and viruses.
CC {ECO:0000269|PubMed:16973618}.
CC -!- DOMAIN: The C-terminal part folds into a super-helical structure and
CC has an extensively positively-charged nucleotide-binding channel on its
CC inner surface.
CC -!- SIMILARITY: Belongs to the IFIT family. {ECO:0000305}.
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DR EMBL; M14660; AAA59191.1; -; Genomic_DNA.
DR EMBL; M14659; AAA59191.1; JOINED; Genomic_DNA.
DR EMBL; AL353751; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X07557; CAA30438.1; -; Genomic_DNA.
DR CCDS; CCDS41548.1; -.
DR PIR; I59087; I59087.
DR RefSeq; NP_001538.4; NM_001547.4.
DR PDB; 4G1T; X-ray; 2.80 A; A/B=1-472.
DR PDBsum; 4G1T; -.
DR AlphaFoldDB; P09913; -.
DR SMR; P09913; -.
DR BioGRID; 109658; 73.
DR DIP; DIP-48848N; -.
DR IntAct; P09913; 40.
DR STRING; 9606.ENSP00000360891; -.
DR GlyGen; P09913; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P09913; -.
DR PhosphoSitePlus; P09913; -.
DR BioMuta; IFIT2; -.
DR DMDM; 124488; -.
DR EPD; P09913; -.
DR jPOST; P09913; -.
DR MassIVE; P09913; -.
DR MaxQB; P09913; -.
DR PaxDb; P09913; -.
DR PeptideAtlas; P09913; -.
DR PRIDE; P09913; -.
DR ProteomicsDB; 52276; -.
DR Antibodypedia; 1277; 209 antibodies from 29 providers.
DR CPTC; P09913; 1 antibody.
DR DNASU; 3433; -.
DR Ensembl; ENST00000371826.4; ENSP00000360891.3; ENSG00000119922.11.
DR Ensembl; ENST00000638108.1; ENSP00000490935.1; ENSG00000119922.11.
DR Ensembl; ENST00000680809.1; ENSP00000506255.1; ENSG00000119922.11.
DR Ensembl; ENST00000680954.1; ENSP00000505033.1; ENSG00000119922.11.
DR GeneID; 3433; -.
DR KEGG; hsa:3433; -.
DR MANE-Select; ENST00000371826.4; ENSP00000360891.3; NM_001547.5; NP_001538.4.
DR UCSC; uc009xts.4; human.
DR CTD; 3433; -.
DR DisGeNET; 3433; -.
DR GeneCards; IFIT2; -.
DR HGNC; HGNC:5409; IFIT2.
DR HPA; ENSG00000119922; Tissue enhanced (bone).
DR MIM; 147040; gene.
DR neXtProt; NX_P09913; -.
DR OpenTargets; ENSG00000119922; -.
DR PharmGKB; PA29650; -.
DR VEuPathDB; HostDB:ENSG00000119922; -.
DR eggNOG; KOG1124; Eukaryota.
DR GeneTree; ENSGT00950000182946; -.
DR HOGENOM; CLU_043482_0_0_1; -.
DR InParanoid; P09913; -.
DR OMA; HIGCCYR; -.
DR OrthoDB; 460948at2759; -.
DR PhylomeDB; P09913; -.
DR TreeFam; TF342671; -.
DR PathwayCommons; P09913; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; P09913; -.
DR BioGRID-ORCS; 3433; 14 hits in 1078 CRISPR screens.
DR ChiTaRS; IFIT2; human.
DR GeneWiki; IFIT2; -.
DR GenomeRNAi; 3433; -.
DR Pharos; P09913; Tbio.
DR PRO; PR:P09913; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P09913; protein.
DR Bgee; ENSG00000119922; Expressed in palpebral conjunctiva and 182 other tissues.
DR ExpressionAtlas; P09913; baseline and differential.
DR Genevisible; P09913; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; TAS:UniProtKB.
DR GO; GO:0035457; P:cellular response to interferon-alpha; IEA:InterPro.
DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:BHF-UCL.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR024124; Interferon-induced_IFIT2.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10271:SF4; PTHR10271:SF4; 1.
DR Pfam; PF13181; TPR_8; 2.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50005; TPR; 1.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Antiviral defense; Apoptosis; Cytoplasm;
KW Endoplasmic reticulum; Immunity; Innate immunity; Reference proteome;
KW Repeat; RNA-binding; TPR repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..472
FT /note="Interferon-induced protein with tetratricopeptide
FT repeats 2"
FT /id="PRO_0000106347"
FT REPEAT 51..89
FT /note="TPR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 90..135
FT /note="TPR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 136..171
FT /note="TPR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 172..208
FT /note="TPR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 247..280
FT /note="TPR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 281..335
FT /note="TPR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 336..366
FT /note="TPR 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 367..405
FT /note="TPR 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REPEAT 406..448
FT /note="TPR 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22825553"
FT REGION 446..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VARIANT 79
FT /note="E -> A (in dbSNP:rs17468739)"
FT /id="VAR_052615"
FT VARIANT 121
FT /note="K -> R (in dbSNP:rs2070845)"
FT /id="VAR_052616"
FT VARIANT 352
FT /note="D -> E (in dbSNP:rs1727)"
FT /id="VAR_014490"
FT MUTAGEN 184
FT /note="R->E: Abolishes RNA-binding."
FT /evidence="ECO:0000269|PubMed:22825553"
FT MUTAGEN 255
FT /note="K->E: Significantly impairs RNA-binding; when
FT associated with Glu-259."
FT /evidence="ECO:0000269|PubMed:22825553"
FT MUTAGEN 259
FT /note="R->E: Significantly impairs RNA-binding; when
FT associated with Glu-255."
FT /evidence="ECO:0000269|PubMed:22825553"
FT MUTAGEN 292
FT /note="R->E: Abolishes RNA-binding."
FT /evidence="ECO:0000269|PubMed:22825553"
FT MUTAGEN 410
FT /note="K->E: Abolishes RNA-binding."
FT /evidence="ECO:0000269|PubMed:22825553"
FT HELIX 9..14
FT /evidence="ECO:0007829|PDB:4G1T"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:4G1T"
FT TURN 24..27
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 31..41
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 52..63
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 67..84
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:4G1T"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 110..126
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 136..149
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 153..167
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 172..187
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 195..204
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 209..221
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 231..242
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 247..259
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 263..276
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 281..300
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 309..329
FT /evidence="ECO:0007829|PDB:4G1T"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 337..346
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 350..362
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 367..383
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 388..400
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 406..425
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 432..445
FT /evidence="ECO:0007829|PDB:4G1T"
FT HELIX 448..451
FT /evidence="ECO:0007829|PDB:4G1T"
SQ SEQUENCE 472 AA; 54632 MW; 3CF11319A5008FB9 CRC64;
MSENNKNSLE SSLRQLKCHF TWNLMEGENS LDDFEDKVFY RTEFQNREFK ATMCNLLAYL
KHLKGQNEAA LECLRKAEEL IQQEHADQAE IRSLVTWGNY AWVYYHMGRL SDVQIYVDKV
KHVCEKFSSP YRIESPELDC EEGWTRLKCG GNQNERAKVC FEKALEKKPK NPEFTSGLAI
ASYRLDNWPP SQNAIDPLRQ AIRLNPDNQY LKVLLALKLH KMREEGEEEG EGEKLVEEAL
EKAPGVTDVL RSAAKFYRRK DEPDKAIELL KKALEYIPNN AYLHCQIGCC YRAKVFQVMN
LRENGMYGKR KLLELIGHAV AHLKKADEAN DNLFRVCSIL ASLHALADQY EDAEYYFQKE
FSKELTPVAK QLLHLRYGNF QLYQMKCEDK AIHHFIEGVK INQKSREKEK MKDKLQKIAK
MRLSKNGADS EALHVLAFLQ ELNEKMQQAD EDSERGLESG SLIPSASSWN GE
