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 24-JAN-2024, entry version 201. 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}. 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; 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; 74. DR DIP; DIP-48848N; -. DR IntAct; P09913; 40. DR STRING; 9606.ENSP00000490935; -. DR GlyCosmos; P09913; 1 site, 1 glycan. 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; 9606-ENSP00000360891; -. DR PeptideAtlas; P09913; -. DR ProteomicsDB; 52276; -. DR Pumba; P09913; -. DR Antibodypedia; 1277; 226 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 AGR; HGNC:5409; -. 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; 5401272at2759; -. 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 1156 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 183 other cell types or tissues. DR ExpressionAtlas; P09913; baseline and differential. 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:0140374; P:antiviral innate immune response; IDA:UniProt. DR GO; GO:0008637; P:apoptotic mitochondrial changes; TAS:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central. 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; 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:SF4; INTERFERON-INDUCED PROTEIN WITH TETRATRICOPEPTIDE REPEATS 2; 1. DR Pfam; PF13181; TPR_8; 2. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; TPR-like; 2. DR PROSITE; PS50005; TPR; 1. DR PROSITE; PS50293; TPR_REGION; 1. DR Genevisible; P09913; HS. 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 //