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O14879

- IFIT3_HUMAN

UniProt

O14879 - IFIT3_HUMAN

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Protein

Interferon-induced protein with tetratricopeptide repeats 3

Gene
IFIT3, CIG-49, IFI60, IFIT4, ISG60
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 IFIT2.5 Publications

GO - Molecular functioni

  1. identical protein binding Source: IntAct
  2. protein binding Source: UniProtKB

GO - Biological processi

  1. cellular response to interferon-alpha Source: InterPro
  2. cytokine-mediated signaling pathway Source: Reactome
  3. defense response to virus Source: UniProtKB-KW
  4. negative regulation of apoptotic process Source: UniProtKB
  5. negative regulation of cell proliferation Source: UniProtKB
  6. response to virus Source: UniProtKB
  7. type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_25162. Interferon alpha/beta signaling.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IFIT3
Synonyms:CIG-49, IFI60, IFIT4, ISG60
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:5411. IFIT3.

Subcellular locationi

Cytoplasm. Mitochondrion 3 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29651.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 490490Interferon-induced protein with tetratricopeptide repeats 3PRO_0000106349Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei203 – 2031Phosphoserine3 Publications
Modified residuei237 – 2371Phosphoserine1 Publication
Modified residuei478 – 4781Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO14879.
PaxDbiO14879.
PeptideAtlasiO14879.
PRIDEiO14879.

PTM databases

PhosphoSiteiO14879.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

By type I interferons, dsRNAs and viruses.1 Publication

Gene expression databases

ArrayExpressiO14879.
BgeeiO14879.
CleanExiHS_IFIT3.
GenevestigatoriO14879.

Organism-specific databases

HPAiHPA059914.

Interactioni

Subunit structurei

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 COPS5.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-745127,EBI-745127
CDC37Q165434EBI-745127,EBI-295634
IFIT1P099145EBI-745127,EBI-745117
IFIT2P099134EBI-745127,EBI-3507167

Protein-protein interaction databases

BioGridi109660. 51 interactions.
IntActiO14879. 50 interactions.
MINTiMINT-1448195.
STRINGi9606.ENSP00000360876.

Structurei

3D structure databases

ProteinModelPortaliO14879.
SMRiO14879. Positions 2-440.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati51 – 8434TPR 1Add
BLAST
Repeati94 – 12734TPR 2Add
BLAST
Repeati136 – 16934TPR 3Add
BLAST
Repeati172 – 20635TPR 4Add
BLAST
Repeati207 – 24034TPR 5Add
BLAST
Repeati241 – 27434TPR 6Add
BLAST
Repeati415 – 44834TPR 7Add
BLAST
Repeati450 – 48132TPR 8Add
BLAST

Sequence similaritiesi

Belongs to the IFIT family.
Contains 8 TPR repeats.

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiNOG284690.
HOGENOMiHOG000001558.
HOVERGENiHBG066330.
InParanoidiO14879.
OMAiHQIGCCY.
OrthoDBiEOG71K62V.
PhylomeDBiO14879.
TreeFamiTF342671.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR024122. Interferon-induced_IFIT3.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10271:SF3. PTHR10271:SF3. 1 hit.
PfamiPF00515. TPR_1. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 4 hits.
[Graphical view]
PROSITEiPS50005. TPR. 5 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O14879-1 [UniParc]FASTAAdd to Basket

« Hide

MSEVTKNSLE KILPQLKCHF TWNLFKEDSV SRDLEDRVCN QIEFLNTEFK    50
ATMYNLLAYI KHLDGNNEAA LECLRQAEEL IQQEHADQAE IRSLVTWGNY 100
AWVYYHLGRL SDAQIYVDKV KQTCKKFSNP YSIEYSELDC EEGWTQLKCG 150
RNERAKVCFE KALEEKPNNP EFSSGLAIAM YHLDNHPEKQ FSTDVLKQAI 200
ELSPDNQYVK VLLGLKLQKM NKEAEGEQFV EEALEKSPCQ TDVLRSAAKF 250
YRRKGDLDKA IELFQRVLES TPNNGYLYHQ IGCCYKAKVR QMQNTGESEA 300
SGNKEMIEAL KQYAMDYSNK ALEKGLNPLN AYSDLAEFLE TECYQTPFNK 350
EVPDAEKQQS HQRYCNLQKY NGKSEDTAVQ HGLEGLSISK KSTDKEEIKD 400
QPQNVSENLL PQNAPNYWYL QGLIHKQNGD LLQAAKCYEK ELGRLLRDAP 450
SGIGSIFLSA SELEDGSEEM GQGAVSSSPR ELLSNSEQLN 490
Length:490
Mass (Da):55,985
Last modified:January 1, 1998 - v1
Checksum:iB9F042D4DF7151D2
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti44 – 441F → S in AAH04977. 1 Publication
Sequence conflicti359 – 3591Q → QQ in AAB40606. 1 Publication
Sequence conflicti435 – 4351Missing in AAB40606. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS31241.1.
CCDS7402.1.
RefSeqiNP_001026853.1. NM_001031683.3.
NP_001540.2. NM_001549.5.
UniGeneiHs.47338.
Hs.744072.

Genome annotation databases

EnsembliENST00000371811; ENSP00000360876; ENSG00000119917.
ENST00000371818; ENSP00000360883; ENSG00000119917.
GeneIDi3437.
KEGGihsa:3437.
UCSCiuc001kgf.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS31241.1.
CCDS7402.1.
RefSeqi NP_001026853.1. NM_001031683.3.
NP_001540.2. NM_001549.5.
UniGenei Hs.47338.
Hs.744072.

3D structure databases

ProteinModelPortali O14879.
SMRi O14879. Positions 2-440.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109660. 51 interactions.
IntActi O14879. 50 interactions.
MINTi MINT-1448195.
STRINGi 9606.ENSP00000360876.

PTM databases

PhosphoSitei O14879.

Proteomic databases

MaxQBi O14879.
PaxDbi O14879.
PeptideAtlasi O14879.
PRIDEi O14879.

Protocols and materials databases

DNASUi 3437.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000371811 ; ENSP00000360876 ; ENSG00000119917 .
ENST00000371818 ; ENSP00000360883 ; ENSG00000119917 .
GeneIDi 3437.
KEGGi hsa:3437.
UCSCi uc001kgf.3. human.

Organism-specific databases

CTDi 3437.
GeneCardsi GC10P091077.
HGNCi HGNC:5411. IFIT3.
HPAi HPA059914.
MIMi 604650. gene.
neXtProti NX_O14879.
PharmGKBi PA29651.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG284690.
HOGENOMi HOG000001558.
HOVERGENi HBG066330.
InParanoidi O14879.
OMAi HQIGCCY.
OrthoDBi EOG71K62V.
PhylomeDBi O14879.
TreeFami TF342671.

Enzyme and pathway databases

Reactomei REACT_25162. Interferon alpha/beta signaling.

Miscellaneous databases

GeneWikii IFIT3.
GenomeRNAii 3437.
NextBioi 13544.
PROi O14879.
SOURCEi Search...

Gene expression databases

ArrayExpressi O14879.
Bgeei O14879.
CleanExi HS_IFIT3.
Genevestigatori O14879.

Family and domain databases

Gene3Di 1.25.40.10. 2 hits.
InterProi IPR024122. Interferon-induced_IFIT3.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view ]
PANTHERi PTHR10271:SF3. PTHR10271:SF3. 1 hit.
Pfami PF00515. TPR_1. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view ]
SMARTi SM00028. TPR. 4 hits.
[Graphical view ]
PROSITEi PS50005. TPR. 5 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. Cited for: REVIEW.
  16. Cited for: FUNCTION, INTERACTION WITH IFIT1 AND IFIT2.

Entry informationi

Entry nameiIFIT3_HUMAN
AccessioniPrimary (citable) accession number: O14879
Secondary accession number(s): Q99634, Q9BSK7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: September 3, 2014
This is version 133 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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