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O14879 (IFIT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 3

Short name=IFIT-3
Alternative name(s):
CIG49
ISG-60
Interferon-induced 60 kDa protein
Short name=IFI-60K
Interferon-induced protein with tetratricopeptide repeats 4
Short name=IFIT-4
Retinoic acid-induced gene G protein
Short name=P60
Short name=RIG-G
Gene names
Name:IFIT3
Synonyms:CIG-49, IFI60, IFIT4, ISG60
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length490 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS-mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exihibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin-dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Upregulates CDKN1A/p21 by downregulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2. Ref.6 Ref.10 Ref.13 Ref.14 Ref.16

Subunit structure

Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT1 and IFIT2. Interacts (via N-terminus) with MAVS, TBK1, TRAF6 and DDX58. Interacts with COPS5. Ref.6 Ref.13 Ref.14 Ref.16

Subcellular location

Cytoplasm. Mitochondrion Ref.6 Ref.7 Ref.14.

Tissue specificity

Expression significantly higher in peripheral blood mononuclear cells (PBMCs) and monocytes from systemic lupus erythematosus (SLE) patients than in those from healthy individuals (at protein level). Spleen, lung, leukocytes, lymph nodes, placenta, bone marrow and fetal liver. Ref.7

Induction

By type I interferons, dsRNAs and viruses. Ref.6

Sequence similarities

Belongs to the IFIT family.

Contains 8 TPR repeats.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 490490Interferon-induced protein with tetratricopeptide repeats 3
PRO_0000106349

Regions

Repeat51 – 8434TPR 1
Repeat94 – 12734TPR 2
Repeat136 – 16934TPR 3
Repeat172 – 20635TPR 4
Repeat207 – 24034TPR 5
Repeat241 – 27434TPR 6
Repeat415 – 44834TPR 7
Repeat450 – 48132TPR 8

Amino acid modifications

Modified residue2031Phosphoserine Ref.8 Ref.9 Ref.11
Modified residue2371Phosphoserine Ref.8
Modified residue4781Phosphoserine Ref.9

Experimental info

Sequence conflict441F → S in AAH04977. Ref.5
Sequence conflict3591Q → QQ in AAB40606. Ref.2
Sequence conflict4351Missing in AAB40606. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O14879 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: B9F042D4DF7151D2

FASTA49055,985
        10         20         30         40         50         60 
MSEVTKNSLE KILPQLKCHF TWNLFKEDSV SRDLEDRVCN QIEFLNTEFK ATMYNLLAYI 

        70         80         90        100        110        120 
KHLDGNNEAA LECLRQAEEL IQQEHADQAE IRSLVTWGNY AWVYYHLGRL SDAQIYVDKV 

       130        140        150        160        170        180 
KQTCKKFSNP YSIEYSELDC EEGWTQLKCG RNERAKVCFE KALEEKPNNP EFSSGLAIAM 

       190        200        210        220        230        240 
YHLDNHPEKQ FSTDVLKQAI ELSPDNQYVK VLLGLKLQKM NKEAEGEQFV EEALEKSPCQ 

       250        260        270        280        290        300 
TDVLRSAAKF YRRKGDLDKA IELFQRVLES TPNNGYLYHQ IGCCYKAKVR QMQNTGESEA 

       310        320        330        340        350        360 
SGNKEMIEAL KQYAMDYSNK ALEKGLNPLN AYSDLAEFLE TECYQTPFNK EVPDAEKQQS 

       370        380        390        400        410        420 
HQRYCNLQKY NGKSEDTAVQ HGLEGLSISK KSTDKEEIKD QPQNVSENLL PQNAPNYWYL 

       430        440        450        460        470        480 
QGLIHKQNGD LLQAAKCYEK ELGRLLRDAP SGIGSIFLSA SELEDGSEEM GQGAVSSSPR 

       490 
ELLSNSEQLN 

« Hide

References

« Hide 'large scale' references
[1]"Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs."
Zhu H., Cong J.-P., Shenk T.
Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Foreskin.
[2]"IFI60/ISG60/IFIT4, a new member of the human IFI54/IFIT2 family of interferon-stimulated genes."
de Veer M.J., Sim H., Whisstock J.C., Devenish R.J., Ralph S.J.
Genomics 54:267-277(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"RIG-G, a novel gene induced by ATRA in acute promyelocytic leukemia cells, is a new member of the ISG family."
Yu M., Tong J., Mao M., Chen S., Chen Z.
Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[6]"RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins."
Xiao S., Li D., Zhu H.Q., Song M.G., Pan X.R., Jia P.M., Peng L.L., Dou A.X., Chen G.Q., Chen S.J., Chen Z., Tong J.H.
Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH COPS5.
[7]"Interferon-induced protein IFIT4 is associated with systemic lupus erythematosus and promotes differentiation of monocytes into dendritic cell-like cells."
Huang X., Shen N., Bao C., Gu Y., Wu L., Chen S.
Arthritis Res. Ther. 10:R91-R91(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-237, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-478, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Identification of alpha interferon-induced genes associated with antiviral activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene."
Schmeisser H., Mejido J., Balinsky C.A., Morrow A.N., Clark C.R., Zhao T., Zoon K.C.
J. Virol. 84:10671-10680(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"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, INTERACTION WITH IFIT2.
[14]"IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1."
Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.
J. Immunol. 187:2559-2568(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAVS; TBK1; TRAF6 AND DDX58.
[15]"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.
[16]"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: FUNCTION, INTERACTION WITH IFIT1 AND IFIT2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF026939 mRNA. Translation: AAB95160.1.
AF083470 mRNA. Translation: AAC63524.1.
U52513 mRNA. Translation: AAB40606.1.
BT007284 mRNA. Translation: AAP35948.1.
BC001383 mRNA. Translation: AAH01383.1.
BC004977 mRNA. Translation: AAH04977.1.
CCDSCCDS31241.1.
CCDS7402.1.
RefSeqNP_001026853.1. NM_001031683.3.
NP_001540.2. NM_001549.5.
UniGeneHs.47338.
Hs.744072.

3D structure databases

ProteinModelPortalO14879.
SMRO14879. Positions 2-440.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109660. 51 interactions.
IntActO14879. 50 interactions.
MINTMINT-1448195.
STRING9606.ENSP00000360876.

PTM databases

PhosphoSiteO14879.

Proteomic databases

MaxQBO14879.
PaxDbO14879.
PeptideAtlasO14879.
PRIDEO14879.

Protocols and materials databases

DNASU3437.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371811; ENSP00000360876; ENSG00000119917.
ENST00000371818; ENSP00000360883; ENSG00000119917.
GeneID3437.
KEGGhsa:3437.
UCSCuc001kgf.3. human.

Organism-specific databases

CTD3437.
GeneCardsGC10P091077.
HGNCHGNC:5411. IFIT3.
HPAHPA059914.
MIM604650. gene.
neXtProtNX_O14879.
PharmGKBPA29651.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG284690.
HOGENOMHOG000001558.
HOVERGENHBG066330.
InParanoidO14879.
OMAHQIGCCY.
OrthoDBEOG71K62V.
PhylomeDBO14879.
TreeFamTF342671.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressO14879.
BgeeO14879.
CleanExHS_IFIT3.
GenevestigatorO14879.

Family and domain databases

Gene3D1.25.40.10. 2 hits.
InterProIPR024122. Interferon-induced_IFIT3.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERPTHR10271:SF3. PTHR10271:SF3. 1 hit.
PfamPF00515. TPR_1. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTSM00028. TPR. 4 hits.
[Graphical view]
PROSITEPS50005. TPR. 5 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiIFIT3.
GenomeRNAi3437.
NextBio13544.
PROO14879.
SOURCESearch...

Entry information

Entry nameIFIT3_HUMAN
AccessionPrimary (citable) accession number: O14879
Secondary accession number(s): Q99634, Q9BSK7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: July 9, 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

MIM cross-references

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

Human chromosome 10

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