O14879 (IFIT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IFIT3
Synonyms:	CIG-49, IFI60, IFIT4, ISG60

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	490 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Innate immunity
Cellular component	Cytoplasm Mitochondrion
Domain	Repeat TPR repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to interferon-alpha Inferred from electronic annotation. Source: InterPro defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptotic process Inferred from direct assay Ref.13. Source: UniProtKB negative regulation of cell proliferation Inferred from direct assay Ref.6. Source: UniProtKB response to virus Inferred from mutant phenotype Ref.16. Source: UniProtKB type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from direct assay Ref.14. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-745127,EBI-745127
CDC37	Q16543	4	EBI-745127,EBI-295634
IFIT1	P09914	5	EBI-745127,EBI-745117
IFIT2	P09913	4	EBI-745127,EBI-3507167

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 490	490	Interferon-induced protein with tetratricopeptide repeats 3		PRO_0000106349
Regions
	Repeat	51 – 84	34	TPR 1
	Repeat	94 – 127	34	TPR 2
	Repeat	136 – 169	34	TPR 3
	Repeat	172 – 206	35	TPR 4
	Repeat	207 – 240	34	TPR 5
	Repeat	241 – 274	34	TPR 6
	Repeat	415 – 448	34	TPR 7
	Repeat	450 – 481	32	TPR 8
Amino acid modifications
	Modified residue	203	1	Phosphoserine Ref.8 Ref.9 Ref.11
	Modified residue	237	1	Phosphoserine Ref.8
	Modified residue	478	1	Phosphoserine Ref.9
Experimental info
	Sequence conflict	44	1	F → S in AAH04977. Ref.5
	Sequence conflict	359	1	Q → QQ in AAB40606. Ref.2
	Sequence conflict	435	1	Missing in AAB40606. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O14879 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: B9F042D4DF7151D2	FASTA	490	55,985
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.
IPI	IPI00024254.
RefSeq	NP_001026853.1. NM_001031683.2. NP_001540.2. NM_001549.4.
UniGene	Hs.744072.
3D structure databases
ProteinModelPortal	O14879.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14879. 49 interactions.
MINT	MINT-1448195.
STRING	9606.ENSP00000360876.
PTM databases
PhosphoSite	O14879.
Proteomic databases
PaxDb	O14879.
PeptideAtlas	O14879.
PRIDE	O14879.
Protocols and materials databases
DNASU	3437.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371811; ENSP00000360876; ENSG00000119917. ENST00000371818; ENSP00000360883; ENSG00000119917.
GeneID	3437.
KEGG	hsa:3437.
UCSC	uc001kgf.3. human.
Organism-specific databases
CTD	3437.
GeneCards	GC10P091077.
HGNC	HGNC:5411. IFIT3.
MIM	604650. gene.
neXtProt	NX_O14879.
PharmGKB	PA29651.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG284690.
HOGENOM	HOG000001558.
HOVERGEN	HBG066330.
InParanoid	O14879.
OMA	LESTPNN.
OrthoDB	EOG4NVZK4.
PhylomeDB	O14879.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	O14879.
Bgee	O14879.
CleanEx	HS_IFIT3.
Genevestigator	O14879.
GermOnline	ENSG00000119917. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 2 hits.
InterPro	IPR024122. Interferon-induced_IFIT3. IPR001440. TPR-1. IPR013026. TPR-contain_dom. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. [Graphical view]
PANTHER	PTHR10271:SF3. PTHR10271:SF3. 1 hit.
Pfam	PF00515. TPR_1. 1 hit. PF13181. TPR_8. 1 hit. [Graphical view]
SMART	SM00028. TPR. 4 hits. [Graphical view]
PROSITE	PS50005. TPR. 5 hits. PS50293. TPR_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3437.
NextBio	13544.
SOURCE	Search...

Entry information

Entry name

IFIT3_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.