Q13325 (IFIT5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon-induced protein with tetratricopeptide repeats 5
Short name=IFIT-5

Alternative name(s):
Interferon-induced 58 kDa protein
Retinoic acid- and interferon-inducible 58 kDa protein
Short name=P58

Gene names

Name:	IFIT5
Synonyms:	ISG58, RI58

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	482 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interferon-induced RNA-binding protein that specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner. Also recognizes and binds tRNAs. Ref.10 Ref.11
Subunit structure	Monomer. Ref.10
Subcellular location	Cell projection › ruffle membrane. Note: Colocalized with DDX58/RIG-I at cell surface ruffles. Localizes to actin-rich protrusions from the apical cell surface. Ref.10
Induction	By interferons (IFNs).
Domain	RNA recognition is mediated by a convoluted intramolecular fold of the TPR repeats (TPR eddy), which scaffolds unique additional helices that form an RNA binding cleft (Ref.10 and Ref.11). Undergoes a conformational change upon RNA-binding: unliganded exists in a more open conformation, facilitating RNA entry (Ref.11).
Sequence similarities	Belongs to the IFIT family. Contains 8 TPR repeats.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Innate immunity
Cellular component	Cell membrane Cell projection Membrane
Domain	Repeat TPR repeat
Ligand	RNA-binding tRNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from mutant phenotype Ref.11. Source: UniProtKB innate immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	actin cytoskeleton Inferred from direct assay Ref.10. Source: UniProtKB apical part of cell Inferred from direct assay Ref.10. Source: UniProtKB ruffle membrane Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	single-stranded RNA binding Inferred from direct assay Ref.11. Source: UniProtKB tRNA binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 482

482

Interferon-induced protein with tetratricopeptide repeats 5

PRO_0000106351

Regions

Repeat

51 – 84

34

TPR 1

Repeat

94 – 127

34

TPR 2

Repeat

138 – 173

36

TPR 3

Repeat

181 – 214

34

TPR 4

Repeat

249 – 282

34

TPR 5

Repeat

338 – 371

34

TPR 6

Repeat

376 – 410

35

TPR 7

Repeat

435 – 468

34

TPR 8

Region

254 – 260

7

Interaction with the 5'-triphosphate group of PPP-RNA

Sites

Site

33

1

Interaction with PPP-RNA

Site

37

1

Interaction with PPP-RNA

Site

41

1

Interaction with PPP-RNA

Site

150

1

Interaction with PPP-RNA

Site

186

1

Interaction with PPP-RNA

Site

250

1

Interaction with PPP-RNA

Site

288

1

Interaction with the 5'-triphosphate group of PPP-RNA

Experimental info

Mutagenesis

33

1

E → A: Reduced PPP-RNA-binding. Ref.11

Mutagenesis

37

1

T → V: Abolishes PPP-RNA-binding.

Mutagenesis

41

1

Q → E: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

150

1

K → M: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

156

1

Y → F: Reduced PPP-RNA-binding. Ref.11

Mutagenesis

186

1

R → H: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

250

1

Y → F: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

253

1

R → M: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

254

1

Y → F: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

260

1

R → E: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

287

1

H → A: Reduced PPP-RNA-binding. Ref.11

Mutagenesis

288

1

Q → E: Abolishes PPP-RNA-binding. Ref.11

Mutagenesis

291

1

L → A: Does not affect RNA-binding. Ref.10

Mutagenesis

302

1

K → A: Reduced RNA-binding. Ref.10

Mutagenesis

307

1

R → A: Reduced RNA-binding. 25 fold reduction in tRNA-binding. Ref.10

Mutagenesis

309

1

K → A: Reduced RNA-binding. Ref.10

Mutagenesis

337

1

F → A: Abolishes PPP-RNA-binding.

Mutagenesis

388 – 389

2

FH → AA: Reduced RNA-binding.

Mutagenesis

415

1

K → A: Reduced RNA-binding. 25 fold reduction in tRNA-binding. Ref.10

Mutagenesis

422

1

K → A: Reduced RNA-binding. Ref.10

Mutagenesis

426

1

K → A: Reduced RNA-binding. 5 fold reduction in tRNA-binding. Ref.10

Sequence conflict

215

1

S → N in CAG33312. Ref.3

Sequence conflict

449

1

G → R in BAG35276. Ref.2

Secondary structure

1

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482

Helix Strand Turn

Details...

Helix

3 – 15

13

Helix

19 – 21

3

Helix

26 – 28

3

Helix

31 – 44

14

Beta strand

46 – 48

3

Helix

50 – 63

14

Helix

67 – 84

18

Helix

86 – 88

3

Helix

91 – 93

3

Helix

94 – 106

13

Helix

110 – 126

17

Beta strand

130 – 133

4

Helix

138 – 150

13

Helix

153 – 155

3

Helix

156 – 169

14

Helix

174 – 189

16

Beta strand

193 – 195

3

Helix

201 – 210

10

Helix

215 – 227

13

Helix

231 – 244

14

Helix

249 – 261

13

Helix

265 – 278

14

Helix

283 – 303

21

Turn

304 – 306

3

Helix

310 – 333

24

Helix

338 – 350

13

Helix

354 – 365

12

Helix

372 – 388

17

Helix

393 – 406

14

Beta strand

408 – 410

3

Helix

413 – 430

18

Helix

435 – 447

13

Helix

451 – 464

14

Helix

469 – 480

12

Sequences

	Sequence		Length	Mass (Da)
	Q13325 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 8045BC100384BE05	FASTA	482	55,847
	10 20 30 40 50 60 MSEIRKDTLK AILLELECHF TWNLLKEDID LFEVEDTIGQ QLEFLTTKSR LALYNLLAYV 70 80 90 100 110 120 KHLKGQNKDA LECLEQAEEI IQQEHSDKEE VRSLVTWGNY AWVYYHMDQL EEAQKYTGKI 130 140 150 160 170 180 GNVCKKLSSP SNYKLECPET DCEKGWALLK FGGKYYQKAK AAFEKALEVE PDNPEFNIGY 190 200 210 220 230 240 AITVYRLDDS DREGSVKSFS LGPLRKAVTL NPDNSYIKVF LALKLQDVHA EAEGEKYIEE 250 260 270 280 290 300 ILDQISSQPY VLRYAAKFYR RKNSWNKALE LLKKALEVTP TSSFLHHQMG LCYRAQMIQI 310 320 330 340 350 360 KKATHNRPKG KDKLKVDELI SSAIFHFKAA MERDSMFAFA YTDLANMYAE GGQYSNAEDI 370 380 390 400 410 420 FRKALRLENI TDDHKHQIHY HYGRFQEFHR KSENTAIHHY LEALKVKDRS PLRTKLTSAL 430 440 450 460 470 480 KKLSTKRLCH NALDVQSLSA LGFVYKLEGE KRQAAEYYEK AQKIDPENAE FLTALCELRL SI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel interferon-inducible gene expressed during myeloid differentiation." Niikura T., Hirata R., Weil S.C. Blood Cells Mol. Dis. 23:337-349(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Pancreas and Spleen.
[7]	"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].
[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: RNA-BINDING.
[10]	"tRNA binding, structure, and localization of the human interferon-induced protein IFIT5." Katibah G.E., Lee H.J., Huizar J.P., Vogan J.M., Alber T., Collins K. Mol. Cell 49:743-750(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF LEU-291; LYS-302; ARG-307; LYS-309; 388-PHE-HIS-389; LYS-415; LYS-422 AND LYS-426.
[11]	"Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins." Abbas Y.M., Pichlmair A., Gorna M.W., Superti-Furga G., Nagar B. Nature 494:60-64(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH PPP-RNA, FUNCTION, RNA-BINDING, MUTAGENESIS OF GLU-33; GLN-41; LYS-150; TYR-156; ARG-186; TYR-250; ARG-253; TYR-254; ARG-260; HIS-287 AND GLN-288.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U34605 mRNA. Translation: AAA84934.1.
AK312358 mRNA. Translation: BAG35276.1.
CR457031 mRNA. Translation: CAG33312.1.
AL353146 Genomic DNA. Translation: CAI12381.1.
CH471066 Genomic DNA. Translation: EAW50135.1.
BC025786 mRNA. Translation: AAH25786.1.

IPI

IPI00012756.

PIR

G02058.

RefSeq

NP_036552.1. NM_012420.2.

UniGene

Hs.252839.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ZGQ	X-ray	2.20	A	1-482	[»]
4HOQ	X-ray	2.07	A	1-482	[»]
4HOR	X-ray	1.86	A	1-482	[»]
4HOS	X-ray	2.00	A	1-482	[»]
4HOT	X-ray	2.50	A	1-482	[»]
4J0U	X-ray	1.97	A	1-482	[»]

ProteinModelPortal

Q13325.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13325. 11 interactions.

MINT

MINT-1395756.

STRING

9606.ENSP00000360860.

PTM databases

PhosphoSite

Q13325.

Polymorphism databases

DMDM

6831571.

Proteomic databases

PaxDb

Q13325.

PeptideAtlas

Q13325.

PRIDE

Q13325.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371795; ENSP00000360860; ENSG00000152778.

GeneID

24138.

KEGG

hsa:24138.

UCSC

uc010qnh.2. human.

Organism-specific databases

CTD

24138.

GeneCards

GC10P091164.

HGNC

HGNC:13328. IFIT5.

HPA

HPA037957.

neXtProt

NX_Q13325.

PharmGKB

PA134988392.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG311487.

HOGENOM

HOG000001558.

HOVERGEN

HBG066330.

InParanoid

Q13325.

OMA

NMYAEGG.

OrthoDB

EOG4V6ZGT.

PhylomeDB

Q13325.

Gene expression databases

ArrayExpress

Q13325.

Bgee

Q13325.

CleanEx

HS_IFIT5.

Genevestigator

Q13325.

GermOnline

ENSG00000152778. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.10. 2 hits.

InterPro

IPR024125. Interferon_induced_IFIT5.
IPR001440. TPR-1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR013105. TPR_2.
IPR019734. TPR_repeat.
[Graphical view]

PANTHER

PTHR10271:SF5. PTHR10271:SF5. 1 hit.

Pfam

PF00515. TPR_1. 1 hit.
PF07719. TPR_2. 2 hits.
[Graphical view]

SMART

SM00028. TPR. 5 hits.
[Graphical view]

PROSITE

PS50005. TPR. 5 hits.
PS50293. TPR_REGION. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

24138.

NextBio

35467534.

Entry information

Entry name

IFIT5_HUMAN

Accession

Primary (citable) accession number: Q13325
Secondary accession number(s): B2R5X9, Q5T7I9, Q6IAX3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 116 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.