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P09913 (IFIT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:IFIT2
Synonyms:CIG-42, G10P2, IFI54, ISG54
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length472 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.9 Ref.11

Subcellular location

Cytoplasm. Endoplasmic reticulum Ref.7.

Induction

By type I interferons, dsRNAs and viruses. Ref.5

Domain

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

Sequence similarities

Belongs to the IFIT family.

Contains 9 TPR repeats.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 472471Interferon-induced protein with tetratricopeptide repeats 2
PRO_0000106347

Regions

Repeat51 – 8939TPR 1
Repeat90 – 13546TPR 2
Repeat136 – 17136TPR 3
Repeat172 – 20837TPR 4
Repeat247 – 28034TPR 5
Repeat281 – 33555TPR 6
Repeat336 – 36631TPR 7
Repeat367 – 40539TPR 8
Repeat406 – 44843TPR 9

Amino acid modifications

Modified residue21N-acetylserine Ref.10

Natural variations

Natural variant791E → A.
Corresponds to variant rs17468739 [ dbSNP | Ensembl ].
VAR_052615
Natural variant1211K → R.
Corresponds to variant rs2070845 [ dbSNP | Ensembl ].
VAR_052616
Natural variant3521D → E.
Corresponds to variant rs1727 [ dbSNP | Ensembl ].
VAR_014490

Experimental info

Mutagenesis1841R → E: Abolishes RNA-binding. Ref.11
Mutagenesis2551K → E: Significantly impairs RNA-binding; when associated with Glu-259. Ref.11
Mutagenesis2591R → E: Significantly impairs RNA-binding; when associated with Glu-255. Ref.11
Mutagenesis2921R → E: Abolishes RNA-binding. Ref.11
Mutagenesis4101K → E: Abolishes RNA-binding. Ref.11

Secondary structure

...................................................... 472
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P09913 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 3CF11319A5008FB9

FASTA47254,632
        10         20         30         40         50         60 
MSENNKNSLE SSLRQLKCHF TWNLMEGENS LDDFEDKVFY RTEFQNREFK ATMCNLLAYL 

        70         80         90        100        110        120 
KHLKGQNEAA LECLRKAEEL IQQEHADQAE IRSLVTWGNY AWVYYHMGRL SDVQIYVDKV 

       130        140        150        160        170        180 
KHVCEKFSSP YRIESPELDC EEGWTRLKCG GNQNERAKVC FEKALEKKPK NPEFTSGLAI 

       190        200        210        220        230        240 
ASYRLDNWPP SQNAIDPLRQ AIRLNPDNQY LKVLLALKLH KMREEGEEEG EGEKLVEEAL 

       250        260        270        280        290        300 
EKAPGVTDVL RSAAKFYRRK DEPDKAIELL KKALEYIPNN AYLHCQIGCC YRAKVFQVMN 

       310        320        330        340        350        360 
LRENGMYGKR KLLELIGHAV AHLKKADEAN DNLFRVCSIL ASLHALADQY EDAEYYFQKE 

       370        380        390        400        410        420 
FSKELTPVAK QLLHLRYGNF QLYQMKCEDK AIHHFIEGVK INQKSREKEK MKDKLQKIAK 

       430        440        450        460        470 
MRLSKNGADS EALHVLAFLQ ELNEKMQQAD EDSERGLESG SLIPSASSWN GE 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The ISG56/IFIT1 gene family."
Fensterl V., Sen G.C.
J. Interferon Cytokine Res. 31:71-78(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA."
Pichlmair A., Lassnig C., Eberle C.A., Gorna M.W., Baumann C.L., Burkard T.R., Buerckstuemmer T., Stefanovic A., Krieger S., Bennett K.L., Ruelicke T., Weber F., Colinge J., Mueller M., Superti-Furga G.
Nat. Immunol. 12:624-630(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IFIT1 AND IFIT3.
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14660, M14659 Genomic DNA. Translation: AAA59191.1.
AL353751 Genomic DNA. Translation: CAI12238.1.
X07557 Genomic DNA. Translation: CAA30438.1.
PIRI59087.
RefSeqNP_001538.4. NM_001547.4.
UniGeneHs.437609.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4G1TX-ray2.80A/B1-472[»]
ProteinModelPortalP09913.
SMRP09913. Positions 8-452.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109658. 37 interactions.
DIPDIP-48848N.
IntActP09913. 32 interactions.
MINTMINT-1479068.
STRING9606.ENSP00000360891.

PTM databases

PhosphoSiteP09913.

Polymorphism databases

DMDM124488.

Proteomic databases

PaxDbP09913.
PRIDEP09913.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371826; ENSP00000360891; ENSG00000119922.
GeneID3433.
KEGGhsa:3433.
UCSCuc009xts.3. human.

Organism-specific databases

CTD3433.
GeneCardsGC10P091051.
H-InvDBHIX0025911.
HGNCHGNC:5409. IFIT2.
HPAHPA003408.
MIM147040. gene.
neXtProtNX_P09913.
PharmGKBPA29650.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG309012.
HOVERGENHBG066330.
InParanoidP09913.
OMAKCEDKAI.
OrthoDBEOG71K62V.
PhylomeDBP09913.
TreeFamTF342671.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP09913.
CleanExHS_IFIT2.
GenevestigatorP09913.

Family and domain databases

Gene3D1.25.40.10. 4 hits.
InterProIPR024124. Interferon-induced_IFIT2.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERPTHR10271:SF4. PTHR10271:SF4. 1 hit.
PfamPF13181. TPR_8. 1 hit.
[Graphical view]
SMARTSM00028. TPR. 3 hits.
[Graphical view]
PROSITEPS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiIFIT2.
GenomeRNAi3433.
NextBio13536.
PROP09913.
SOURCESearch...

Entry information

Entry nameIFIT2_HUMAN
AccessionPrimary (citable) accession number: P09913
Secondary accession number(s): Q5T767
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM