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P09913

- IFIT2_HUMAN

UniProt

P09913 - IFIT2_HUMAN

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Protein

Interferon-induced protein with tetratricopeptide repeats 2

Gene
IFIT2, CIG-42, G10P2, IFI54, ISG54
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. poly(A) RNA binding Source: UniProtKB
  2. protein binding Source: UniProtKB

GO - Biological processi

  1. apoptotic mitochondrial changes Source: UniProtKB
  2. cellular response to interferon-alpha Source: Ensembl
  3. cytokine-mediated signaling pathway Source: Reactome
  4. defense response to virus Source: UniProtKB-KW
  5. negative regulation of protein binding Source: BHF-UCL
  6. positive regulation of apoptotic process Source: UniProtKB
  7. response to virus Source: UniProtKB
  8. 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: Chromosome 10

Organism-specific databases

HGNCiHGNC:5409. IFIT2.

Subcellular locationi

Cytoplasm. Endoplasmic reticulum 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. 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.

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.
GenevestigatoriP09913.

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. 37 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 – 146
Turni19 – 213
Turni24 – 274
Helixi31 – 4111
Helixi52 – 6312
Helixi67 – 8418
Helixi86 – 883
Turni90 – 934
Helixi94 – 10613
Helixi110 – 12617
Helixi136 – 14914
Helixi153 – 16715
Helixi172 – 18716
Helixi195 – 20410
Helixi209 – 22113
Helixi231 – 24212
Helixi247 – 25913
Helixi263 – 27614
Helixi281 – 30020
Helixi309 – 32921
Turni331 – 3333
Helixi337 – 34610
Helixi350 – 36213
Helixi367 – 38317
Helixi388 – 40013
Helixi406 – 42520
Helixi432 – 44514

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4G1TX-ray2.80A/B1-472[»]
ProteinModelPortaliP09913.
SMRiP09913. Positions 8-452.

Family & Domainsi

Domains and Repeats

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

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiNOG309012.
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.
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

MSENNKNSLE SSLRQLKCHF TWNLMEGENS LDDFEDKVFY RTEFQNREFK    50
ATMCNLLAYL KHLKGQNEAA LECLRKAEEL IQQEHADQAE IRSLVTWGNY 100
AWVYYHMGRL SDVQIYVDKV KHVCEKFSSP YRIESPELDC EEGWTRLKCG 150
GNQNERAKVC FEKALEKKPK NPEFTSGLAI ASYRLDNWPP SQNAIDPLRQ 200
AIRLNPDNQY LKVLLALKLH KMREEGEEEG EGEKLVEEAL EKAPGVTDVL 250
RSAAKFYRRK DEPDKAIELL KKALEYIPNN AYLHCQIGCC YRAKVFQVMN 300
LRENGMYGKR KLLELIGHAV AHLKKADEAN DNLFRVCSIL ASLHALADQY 350
EDAEYYFQKE FSKELTPVAK QLLHLRYGNF QLYQMKCEDK AIHHFIEGVK 400
INQKSREKEK MKDKLQKIAK MRLSKNGADS EALHVLAFLQ ELNEKMQQAD 450
EDSERGLESG SLIPSASSWN GE 472
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:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi124488.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M14660 , M14659 Genomic DNA. Translation: AAA59191.1 .
AL353751 Genomic DNA. Translation: CAI12238.1 .
X07557 Genomic DNA. Translation: CAA30438.1 .
CCDSi CCDS41548.1.
PIRi I59087.
RefSeqi NP_001538.4. NM_001547.4.
UniGenei Hs.437609.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4G1T X-ray 2.80 A/B 1-472 [» ]
ProteinModelPortali P09913.
SMRi P09913. Positions 8-452.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109658. 37 interactions.
DIPi DIP-48848N.
IntActi P09913. 32 interactions.
MINTi MINT-1479068.
STRINGi 9606.ENSP00000360891.

PTM databases

PhosphoSitei P09913.

Polymorphism databases

DMDMi 124488.

Proteomic databases

MaxQBi P09913.
PaxDbi P09913.
PRIDEi P09913.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000371826 ; ENSP00000360891 ; ENSG00000119922 .
GeneIDi 3433.
KEGGi hsa:3433.
UCSCi uc009xts.3. human.

Organism-specific databases

CTDi 3433.
GeneCardsi GC10P091051.
H-InvDB HIX0025911.
HGNCi HGNC:5409. IFIT2.
HPAi HPA003408.
MIMi 147040. gene.
neXtProti NX_P09913.
PharmGKBi PA29650.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG309012.
HOVERGENi HBG066330.
InParanoidi P09913.
OMAi KCEDKAI.
OrthoDBi EOG71K62V.
PhylomeDBi P09913.
TreeFami TF342671.

Enzyme and pathway databases

Reactomei REACT_25162. Interferon alpha/beta signaling.

Miscellaneous databases

GeneWikii IFIT2.
GenomeRNAii 3433.
NextBioi 13536.
PROi P09913.
SOURCEi Search...

Gene expression databases

Bgeei P09913.
CleanExi HS_IFIT2.
Genevestigatori P09913.

Family and domain databases

Gene3Di 1.25.40.10. 4 hits.
InterProi IPR024124. Interferon-induced_IFIT2.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view ]
PANTHERi PTHR10271:SF4. PTHR10271:SF4. 1 hit.
Pfami PF13181. TPR_8. 1 hit.
[Graphical view ]
SMARTi SM00028. TPR. 3 hits.
[Graphical view ]
PROSITEi PS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 136 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

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