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Protein

Interferon-induced protein with tetratricopeptide repeats 2

Gene

IFIT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

IFN-induced antiviral protein which inhibits expression of viral messenger RNAs lacking 2'-O-methylation of the 5' cap. The ribose 2'-O-methylation would provide a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Binds AU-rich viral RNAs, with or without 5' triphosphorylation, RNA-binding is required for antiviral activity. Can promote apoptosis.1 Publication

GO - Molecular functioni

  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • apoptotic mitochondrial changes Source: UniProtKB
  • cellular response to interferon-alpha Source: Ensembl
  • cytokine-mediated signaling pathway Source: Reactome
  • defense response to virus Source: UniProtKB-KW
  • negative regulation of protein binding Source: BHF-UCL
  • positive regulation of apoptotic process Source: UniProtKB
  • response to virus Source: UniProtKB
  • type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Apoptosis, Immunity, Innate immunity

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiREACT_25162. Interferon alpha/beta signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-induced protein with tetratricopeptide repeats 2
Short name:
IFIT-2
Alternative name(s):
ISG-54 K
Interferon-induced 54 kDa protein
Short name:
IFI-54K
Short name:
P54
Gene namesi
Name:IFIT2
Synonyms:CIG-42, G10P2, IFI54, ISG54
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:5409. IFIT2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endoplasmic reticulum Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi184 – 1841R → E: Abolishes RNA-binding. 1 Publication
Mutagenesisi255 – 2551K → E: Significantly impairs RNA-binding; when associated with Glu-259. 1 Publication
Mutagenesisi259 – 2591R → E: Significantly impairs RNA-binding; when associated with Glu-255. 1 Publication
Mutagenesisi292 – 2921R → E: Abolishes RNA-binding. 1 Publication
Mutagenesisi410 – 4101K → E: Abolishes RNA-binding. 1 Publication

Organism-specific databases

PharmGKBiPA29650.

Polymorphism and mutation databases

BioMutaiIFIT2.
DMDMi124488.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 472471Interferon-induced protein with tetratricopeptide repeats 2PRO_0000106347Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP09913.
PaxDbiP09913.
PRIDEiP09913.

PTM databases

PhosphoSiteiP09913.

Expressioni

Inductioni

By type I interferons, dsRNAs and viruses.1 Publication

Gene expression databases

BgeeiP09913.
CleanExiHS_IFIT2.
ExpressionAtlasiP09913. baseline and differential.
GenevisibleiP09913. HS.

Organism-specific databases

HPAiHPA003408.

Interactioni

Subunit structurei

Domain-swapped homodimer. Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT1 and IFIT3. Interacts with TMEM173/MITA and disrupts its interaction with MAVS or TBK1. Interacts with EIF3E and EIF3C.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IFIT1P099145EBI-3507167,EBI-745117
IFIT3O148794EBI-3507167,EBI-745127

Protein-protein interaction databases

BioGridi109658. 39 interactions.
DIPiDIP-48848N.
IntActiP09913. 32 interactions.
MINTiMINT-1479068.
STRINGi9606.ENSP00000360891.

Structurei

Secondary structure

1
472
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 146Combined sources
Turni19 – 213Combined sources
Turni24 – 274Combined sources
Helixi31 – 4111Combined sources
Helixi52 – 6312Combined sources
Helixi67 – 8418Combined sources
Helixi86 – 883Combined sources
Turni90 – 934Combined sources
Helixi94 – 10613Combined sources
Helixi110 – 12617Combined sources
Helixi136 – 14914Combined sources
Helixi153 – 16715Combined sources
Helixi172 – 18716Combined sources
Helixi195 – 20410Combined sources
Helixi209 – 22113Combined sources
Helixi231 – 24212Combined sources
Helixi247 – 25913Combined sources
Helixi263 – 27614Combined sources
Helixi281 – 30020Combined sources
Helixi309 – 32921Combined sources
Turni331 – 3333Combined sources
Helixi337 – 34610Combined sources
Helixi350 – 36213Combined sources
Helixi367 – 38317Combined sources
Helixi388 – 40013Combined sources
Helixi406 – 42520Combined sources
Helixi432 – 44514Combined sources
Helixi448 – 4514Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4G1TX-ray2.80A/B1-472[»]
ProteinModelPortaliP09913.
SMRiP09913. Positions 8-452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati51 – 8939TPR 1PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati90 – 13546TPR 2PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati136 – 17136TPR 3PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati172 – 20837TPR 4PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati247 – 28034TPR 5PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati281 – 33555TPR 6PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati336 – 36631TPR 7PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati367 – 40539TPR 8PROSITE-ProRule annotation1 PublicationAdd
BLAST
Repeati406 – 44843TPR 9PROSITE-ProRule annotation1 PublicationAdd
BLAST

Domaini

The C-terminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface.

Sequence similaritiesi

Belongs to the IFIT family.Curated
Contains 9 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiNOG309012.
GeneTreeiENSGT00390000013876.
HOVERGENiHBG066330.
InParanoidiP09913.
OMAiKCEDKAI.
OrthoDBiEOG71K62V.
PhylomeDBiP09913.
TreeFamiTF342671.

Family and domain databases

Gene3Di1.25.40.10. 4 hits.
InterProiIPR024124. Interferon-induced_IFIT2.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10271:SF4. PTHR10271:SF4. 1 hit.
PfamiPF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
PROSITEiPS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09913-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSENNKNSLE SSLRQLKCHF TWNLMEGENS LDDFEDKVFY RTEFQNREFK
60 70 80 90 100
ATMCNLLAYL KHLKGQNEAA LECLRKAEEL IQQEHADQAE IRSLVTWGNY
110 120 130 140 150
AWVYYHMGRL SDVQIYVDKV KHVCEKFSSP YRIESPELDC EEGWTRLKCG
160 170 180 190 200
GNQNERAKVC FEKALEKKPK NPEFTSGLAI ASYRLDNWPP SQNAIDPLRQ
210 220 230 240 250
AIRLNPDNQY LKVLLALKLH KMREEGEEEG EGEKLVEEAL EKAPGVTDVL
260 270 280 290 300
RSAAKFYRRK DEPDKAIELL KKALEYIPNN AYLHCQIGCC YRAKVFQVMN
310 320 330 340 350
LRENGMYGKR KLLELIGHAV AHLKKADEAN DNLFRVCSIL ASLHALADQY
360 370 380 390 400
EDAEYYFQKE FSKELTPVAK QLLHLRYGNF QLYQMKCEDK AIHHFIEGVK
410 420 430 440 450
INQKSREKEK MKDKLQKIAK MRLSKNGADS EALHVLAFLQ ELNEKMQQAD
460 470
EDSERGLESG SLIPSASSWN GE
Length:472
Mass (Da):54,632
Last modified:July 1, 1989 - v1
Checksum:i3CF11319A5008FB9
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti79 – 791E → A.
Corresponds to variant rs17468739 [ dbSNP | Ensembl ].
VAR_052615
Natural varianti121 – 1211K → R.
Corresponds to variant rs2070845 [ dbSNP | Ensembl ].
VAR_052616
Natural varianti352 – 3521D → E.
Corresponds to variant rs1727 [ dbSNP | Ensembl ].
VAR_014490

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14660, M14659 Genomic DNA. Translation: AAA59191.1.
AL353751 Genomic DNA. Translation: CAI12238.1.
X07557 Genomic DNA. Translation: CAA30438.1.
CCDSiCCDS41548.1.
PIRiI59087.
RefSeqiNP_001538.4. NM_001547.4.
UniGeneiHs.437609.

Genome annotation databases

EnsembliENST00000371826; ENSP00000360891; ENSG00000119922.
GeneIDi3433.
KEGGihsa:3433.
UCSCiuc009xts.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14660, M14659 Genomic DNA. Translation: AAA59191.1.
AL353751 Genomic DNA. Translation: CAI12238.1.
X07557 Genomic DNA. Translation: CAA30438.1.
CCDSiCCDS41548.1.
PIRiI59087.
RefSeqiNP_001538.4. NM_001547.4.
UniGeneiHs.437609.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4G1TX-ray2.80A/B1-472[»]
ProteinModelPortaliP09913.
SMRiP09913. Positions 8-452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109658. 39 interactions.
DIPiDIP-48848N.
IntActiP09913. 32 interactions.
MINTiMINT-1479068.
STRINGi9606.ENSP00000360891.

PTM databases

PhosphoSiteiP09913.

Polymorphism and mutation databases

BioMutaiIFIT2.
DMDMi124488.

Proteomic databases

MaxQBiP09913.
PaxDbiP09913.
PRIDEiP09913.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371826; ENSP00000360891; ENSG00000119922.
GeneIDi3433.
KEGGihsa:3433.
UCSCiuc009xts.3. human.

Organism-specific databases

CTDi3433.
GeneCardsiGC10P091051.
H-InvDBHIX0025911.
HGNCiHGNC:5409. IFIT2.
HPAiHPA003408.
MIMi147040. gene.
neXtProtiNX_P09913.
PharmGKBiPA29650.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG309012.
GeneTreeiENSGT00390000013876.
HOVERGENiHBG066330.
InParanoidiP09913.
OMAiKCEDKAI.
OrthoDBiEOG71K62V.
PhylomeDBiP09913.
TreeFamiTF342671.

Enzyme and pathway databases

ReactomeiREACT_25162. Interferon alpha/beta signaling.

Miscellaneous databases

GeneWikiiIFIT2.
GenomeRNAii3433.
NextBioi13536.
PROiP09913.
SOURCEiSearch...

Gene expression databases

BgeeiP09913.
CleanExiHS_IFIT2.
ExpressionAtlasiP09913. baseline and differential.
GenevisibleiP09913. HS.

Family and domain databases

Gene3Di1.25.40.10. 4 hits.
InterProiIPR024124. Interferon-induced_IFIT2.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10271:SF4. PTHR10271:SF4. 1 hit.
PfamiPF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
PROSITEiPS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region."
    Levy D., Larner A., Chaudhuri A., Babiss L.E., Darnell J.E. Jr.
    Proc. Natl. Acad. Sci. U.S.A. 83:8929-8933(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Regulation of two interferon-inducible human genes by interferon, poly(rI).poly(rC) and viruses."
    Wathelet M.G., Clauss I.M., Content J., Huez G.A.
    Eur. J. Biochem. 174:323-329(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2.
  4. "The IFI-56K and IFI-54K interferon-inducible human genes belong to the same gene family."
    Wathelet M.G., Clauss I.M., Content J., Huez G.A.
    FEBS Lett. 231:164-171(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: SIMILARITY TO IFI-56K.
  5. "Distinct induction patterns and functions of two closely related interferon-inducible human genes, ISG54 and ISG56."
    Terenzi F., Hui D.J., Merrick W.C., Sen G.C.
    J. Biol. Chem. 281:34064-34071(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, INTERACTION WITH EIF3E AND EIF3C.
  6. "ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response."
    Li Y., Li C., Xue P., Zhong B., Mao A.P., Ran Y., Chen H., Wang Y.Y., Yang F., Shu H.B.
    Proc. Natl. Acad. Sci. U.S.A. 106:7945-7950(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TMEM173/MITA.
  7. "The interferon stimulated gene 54 promotes apoptosis."
    Stawowczyk M., Van Scoy S., Kumar K.P., Reich N.C.
    J. Biol. Chem. 286:7257-7266(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IFIT1 AND IFIT3.
  8. Cited for: REVIEW.
  9. Cited for: INTERACTION WITH IFIT1 AND IFIT3.
  10. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  11. "Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms."
    Yang Z., Liang H., Zhou Q., Li Y., Chen H., Ye W., Chen D., Fleming J., Shu H., Liu Y.
    Cell Res. 22:1328-1338(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), TPR REPEATS, SUBUNIT, MUTAGENESIS OF ARG-184; LYS-255; ARG-259; ARG-292 AND LYS-410.

Entry informationi

Entry nameiIFIT2_HUMAN
AccessioniPrimary (citable) accession number: P09913
Secondary accession number(s): Q5T767
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: June 24, 2015
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.