P09913 (IFIT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IFIT2
Synonyms:	CIG-42, G10P2, IFI54, ISG54

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	472 AA.
Sequence status	Complete.
Protein existence	Evidence 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.10
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.

Ontologies

Keywords
Biological process	Antiviral defense Apoptosis Immunity Innate immunity
Cellular component	Cytoplasm Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Domain	Repeat TPR repeat
Ligand	RNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic mitochondrial changes Traceable author statement Ref.7. Source: UniProtKB cellular response to interferon-alpha Inferred from electronic annotation. Source: Compara defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of protein binding Inferred from direct assay Ref.6. Source: BHF-UCL positive regulation of apoptotic process Inferred from direct assay Ref.7. Source: UniProtKB response to virus Inferred from mutant phenotype Ref.9. Source: UniProtKB type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome endoplasmic reticulum Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IFIT1	P09914	5	EBI-3507167,EBI-745117
IFIT3	O14879	4	EBI-3507167,EBI-745127

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 472

472

Interferon-induced protein with tetratricopeptide repeats 2

PRO_0000106347

Regions

Repeat

51 – 89

39

TPR 1

Repeat

90 – 135

46

TPR 2

Repeat

136 – 171

36

TPR 3

Repeat

172 – 208

37

TPR 4

Repeat

247 – 280

34

TPR 5

Repeat

281 – 335

55

TPR 6

Repeat

336 – 366

31

TPR 7

Repeat

367 – 405

39

TPR 8

Repeat

406 – 448

43

TPR 9

Natural variations

Natural variant

79

1

E → A.
Corresponds to variant rs17468739 [ dbSNP | Ensembl ].

VAR_052615

Natural variant

121

1

K → R.
Corresponds to variant rs2070845 [ dbSNP | Ensembl ].

VAR_052616

Natural variant

352

1

D → E.
Corresponds to variant rs1727 [ dbSNP | Ensembl ].

VAR_014490

Experimental info

Mutagenesis

184

1

R → E: Abolishes RNA-binding. Ref.10

Mutagenesis

255

1

K → E: Significantly impairs RNA-binding; when associated with Glu-259. Ref.10

Mutagenesis

259

1

R → E: Significantly impairs RNA-binding; when associated with Glu-255. Ref.10

Mutagenesis

292

1

R → E: Abolishes RNA-binding. Ref.10

Mutagenesis

410

1

K → E: Abolishes RNA-binding. Ref.10

Secondary structure

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472

Helix Strand Turn

Details...

Helix

9 – 14

6

Turn

19 – 21

3

Turn

24 – 27

4

Helix

31 – 41

11

Helix

52 – 63

12

Helix

67 – 84

18

Helix

86 – 88

3

Turn

90 – 93

4

Helix

94 – 106

13

Helix

110 – 126

17

Helix

136 – 149

14

Helix

153 – 167

15

Helix

172 – 187

16

Helix

195 – 204

10

Helix

209 – 221

13

Helix

231 – 242

12

Helix

247 – 259

13

Helix

263 – 276

14

Helix

281 – 300

20

Helix

309 – 329

21

Turn

331 – 333

3

Helix

337 – 346

10

Helix

350 – 362

13

Helix

367 – 383

17

Helix

388 – 400

13

Helix

406 – 425

20

Helix

432 – 445

14

Sequences

	Sequence		Length	Mass (Da)
	P09913 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 3CF11319A5008FB9	FASTA	472	54,632
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.

IPI

IPI00018298.

PIR

I59087.

RefSeq

NP_001538.4. NM_001547.4.

UniGene

Hs.437609.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4G1T	X-ray	2.80	A/B	1-472	[»]

ProteinModelPortal

P09913.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48848N.

IntAct

P09913. 32 interactions.

MINT

MINT-1479068.

STRING

9606.ENSP00000360891.

PTM databases

PhosphoSite

P09913.

Polymorphism databases

DMDM

124488.

Proteomic databases

PaxDb

P09913.

PRIDE

P09913.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371826; ENSP00000360891; ENSG00000119922.

GeneID

3433.

KEGG

hsa:3433.

UCSC

uc009xts.3. human.

Organism-specific databases

CTD

3433.

GeneCards

GC10P091051.

H-InvDB

HIX0025911.

HGNC

HGNC:5409. IFIT2.

HPA

HPA003408.

MIM

147040. gene.

neXtProt

NX_P09913.

PharmGKB

PA29650.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG309012.

HOVERGEN

HBG066330.

InParanoid

P09913.

OMA

EYYFQKE.

OrthoDB

EOG4NVZK4.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

P09913.

CleanEx

HS_IFIT2.

Genevestigator

P09913.

GermOnline

ENSG00000119922. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.10. 4 hits.

InterPro

IPR024124. Interferon-induced_IFIT2.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]

PANTHER

PTHR10271:SF4. PTHR10271:SF4. 1 hit.

Pfam

PF13181. TPR_8. 1 hit.
[Graphical view]

SMART

SM00028. TPR. 3 hits.
[Graphical view]

PROSITE

PS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

3433.

NextBio

13536.

SOURCE

Search...

Entry information

Entry name

IFIT2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 125 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.