Reviewed, UniProtKB/Swiss-Prot O95786 (DDX58_HUMAN)

Names and origin

Protein names

Recommended name:
    Probable ATP-dependent RNA helicase DDX58
    EC=3.6.1.-
Alternative name(s):
    DEAD-box protein 58
    Retinoic acid-inducible gene 1 protein
      Short name=RIG-1
      Short name=RIG-I

Gene names

Name:

DDX58

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	925 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in innate immune defense against viruses. Upon interaction with intracellular dsRNA produced during viral replication, triggers a transduction cascade involving MAVS/IPS1, which results in the activation of NF-kappa-B, IRF3 and IRF7 and the induction of the expression of antiviral cytokines such as IFN-beta and RANTES (CCL5). Essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza viruses, Japanese encephalitis virus and HCV By similarity.
Subunit structure	Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts with MAVS. Interacts with DHX58/LGP2, IKBKE, TBK1 and TMEM173/STING. Ref.8 Ref.9 Ref.11 Ref.12 Ref.14 Ref.15
Subcellular location	Cytoplasm. Ref.5 Ref.6 Ref.7
Tissue specificity	Present in vascular smooth cells (at protein level). Ref.6
Induction	By bacterial lipopolysaccharide (LPS) in endothelial cells. By IFN-alpha, -beta and -gamma. Ref.5 Ref.6 Ref.7 Ref.2 Ref.10
Domain	The repressor domain controls homomultimerization and interaction with MAVS Probable. The helicase domain is responsible for dsRNA recognition. Ref.14 The 2 CARD domains are responsible for interaction with and signaling through MAVS. Ref.14
Post-translational modification	Isgylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation.
Sequence similarities	Belongs to the helicase family. Contains 2 CARD domains. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	Antiviral defense Immune response Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Helicase Hydrolase
PTM	Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	innate immune response Inferred from electronic annotation. Source: UniProtKB-KW response to virus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro RNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAVS	Q7Z434	1	EBI-995350,EBI-995373

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95786-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95786-2)

The sequence of this isoform differs from the canonical sequence as follows:
     36-80: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 925

925

Probable ATP-dependent RNA helicase DDX58

PRO_0000144093

Regions

Domain

1 – 87

87

CARD 1

Domain

92 – 172

81

CARD 2

Domain

251 – 430

180

Helicase ATP-binding

Domain

610 – 776

167

Helicase C-terminal

Nucleotide binding

264 – 271

8

ATP Probable

Region

735 – 925

191

Repressor domain

Motif

372 – 375

4

DECH box

Natural variations

Alternative sequence

36 – 80

45

Missing in isoform 2.

VSP_016054

Natural variant

7

1

R → C: dbSNP rs10813831. Ref.4

VAR_023747

Natural variant

580

1

D → E: dbSNP rs17217280. Ref.2 Ref.1

VAR_023748

Experimental info

Mutagenesis

55

1

T → I: No IRF3 signaling activity; no effect on dsRNA binding. Ref.10

Mutagenesis

270

1

K → A: No IRF3 signaling activity. Ref.7 Ref.10

Secondary structure

1

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925

Helix Strand Turn

Details...

Beta strand

807 – 810

4

Turn

811 – 813

3

Beta strand

816 – 819

4

Helix

820 – 822

3

Beta strand

823 – 826

4

Turn

827 – 829

3

Beta strand

830 – 833

4

Helix

836 – 841

6

Beta strand

842 – 846

5

Beta strand

854 – 864

11

Turn

867 – 869

3

Beta strand

872 – 879

8

Beta strand

882 – 887

6

Helix

889 – 891

3

Beta strand

892 – 895

4

Turn

897 – 899

3

Helix

908 – 910

3

Turn

920 – 922

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 8, 2005. Version 2. Checksum: BF0D501C395BAE25	FASTA	925	106,600
	10 20 30 40 50 60 MTTEQRRSLQ AFQDYIRKTL DPTYILSYMA PWFREEEVQY IQAEKNNKGP MEAATLFLKF 70 80 90 100 110 120 LLELQEEGWF RGFLDALDHA GYSGLYEAIE SWDFKKIEKL EEYRLLLKRL QPEFKTRIIP 130 140 150 160 170 180 TDIISDLSEC LINQECEEIL QICSTKGMMA GAEKLVECLL RSDKENWPKT LKLALEKERN 190 200 210 220 230 240 KFSELWIVEK GIKDVETEDL EDKMETSDIQ IFYQEDPECQ NLSENSCPPS EVSDTNLYSP 250 260 270 280 290 300 FKPRNYQLEL ALPAMKGKNT IICAPTGCGK TFVSLLICEH HLKKFPQGQK GKVVFFANQI 310 320 330 340 350 360 PVYEQQKSVF SKYFERHGYR VTGISGATAE NVPVEQIVEN NDIIILTPQI LVNNLKKGTI 370 380 390 400 410 420 PSLSIFTLMI FDECHNTSKQ HPYNMIMFNY LDQKLGGSSG PLPQVIGLTA SVGVGDAKNT 430 440 450 460 470 480 DEALDYICKL CASLDASVIA TVKHNLEELE QVVYKPQKFF RKVESRISDK FKYIIAQLMR 490 500 510 520 530 540 DTESLAKRIC KDLENLSQIQ NREFGTQKYE QWIVTVQKAC MVFQMPDKDE ESRICKALFL 550 560 570 580 590 600 YTSHLRKYND ALIISEHARM KDALDYLKDF FSNVRAAGFD EIEQDLTQRF EEKLQELESV 610 620 630 640 650 660 SRDPSNENPK LEDLCFILQE EYHLNPETIT ILFVKTRALV DALKNWIEGN PKLSFLKPGI 670 680 690 700 710 720 LTGRGKTNQN TGMTLPAQKC ILDAFKASGD HNILIATSVA DEGIDIAQCN LVILYEYVGN 730 740 750 760 770 780 VIKMIQTRGR GRARGSKCFL LTSNAGVIEK EQINMYKEKM MNDSILRLQT WDEAVFREKI 790 800 810 820 830 840 LHIQTHEKFI RDSQEKPKPV PDKENKKLLC RKCKALACYT ADVRVIEECH YTVLGDAFKE 850 860 870 880 890 900 CFVSRPHPKP KQFSSFEKRA KIFCARQNCS HDWGIHVKYK TFEIPVIKIE SFVVEDIATG 910 920 VQTLYSKWKD FHFEKIPFDP AEMSK
	Isoform 2. Checksum: 4B1603B6F2F37A66	FASTA	880	101,377
	10 20 30 40 50 60 MTTEQRRSLQ AFQDYIRKTL DPTYILSYMA PWFREGYSGL YEAIESWDFK KIEKLEEYRL 70 80 90 100 110 120 LLKRLQPEFK TRIIPTDIIS DLSECLINQE CEEILQICST KGMMAGAEKL VECLLRSDKE 130 140 150 160 170 180 NWPKTLKLAL EKERNKFSEL WIVEKGIKDV ETEDLEDKME TSDIQIFYQE DPECQNLSEN 190 200 210 220 230 240 SCPPSEVSDT NLYSPFKPRN YQLELALPAM KGKNTIICAP TGCGKTFVSL LICEHHLKKF 250 260 270 280 290 300 PQGQKGKVVF FANQIPVYEQ QKSVFSKYFE RHGYRVTGIS GATAENVPVE QIVENNDIII 310 320 330 340 350 360 LTPQILVNNL KKGTIPSLSI FTLMIFDECH NTSKQHPYNM IMFNYLDQKL GGSSGPLPQV 370 380 390 400 410 420 IGLTASVGVG DAKNTDEALD YICKLCASLD ASVIATVKHN LEELEQVVYK PQKFFRKVES 430 440 450 460 470 480 RISDKFKYII AQLMRDTESL AKRICKDLEN LSQIQNREFG TQKYEQWIVT VQKACMVFQM 490 500 510 520 530 540 PDKDEESRIC KALFLYTSHL RKYNDALIIS EHARMKDALD YLKDFFSNVR AAGFDEIEQD 550 560 570 580 590 600 LTQRFEEKLQ ELESVSRDPS NENPKLEDLC FILQEEYHLN PETITILFVK TRALVDALKN 610 620 630 640 650 660 WIEGNPKLSF LKPGILTGRG KTNQNTGMTL PAQKCILDAF KASGDHNILI ATSVADEGID 670 680 690 700 710 720 IAQCNLVILY EYVGNVIKMI QTRGRGRARG SKCFLLTSNA GVIEKEQINM YKEKMMNDSI 730 740 750 760 770 780 LRLQTWDEAV FREKILHIQT HEKFIRDSQE KPKPVPDKEN KKLLCRKCKA LACYTADVRV 790 800 810 820 830 840 IEECHYTVLG DAFKECFVSR PHPKPKQFSS FEKRAKIFCA RQNCSHDWGI HVKYKTFEIP 850 860 870 880 VIKIESFVVE DIATGVQTLY SKWKDFHFEK IPFDPAEMSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"RIG-I, a human homolog gene of RNA helicase, is induced by retinoic acid during the differentiation of acute promyelocytic leukemia cell." Sun Y.-W. Thesis (1997), Shanghai Institute of Hematology, China Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-580.
[2]	"Retinoic acid-inducible gene-I is induced in endothelial cells by LPS and regulates expression of COX-2." Imaizumi T., Aratani S., Nakajima T., Carlson M., Matsumiya T., Tanji K., Ookawa K., Yoshida H., Tsuchida S., McIntyre T.M., Prescott S.M., Zimmerman G.A., Satoh K. Biochem. Biophys. Res. Commun. 292:274-279(2002) [PubMed: 11890704] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-580, INDUCTION.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-748 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 528-925 (ISOFORMS 1/2), VARIANT CYS-7. Tissue: Skin and Testis.
[5]	"Retinoic acid-inducible gene-I is induced by interferon-gamma and regulates the expression of interferon-gamma stimulated gene 15 in MCF-7 cells." Cui X.-F., Imaizumi T., Yoshida H., Borden E.C., Satoh K. Biochem. Cell Biol. 82:401-405(2004) [PubMed: 15181474] [Abstract] Cited for: INDUCTION, SUBCELLULAR LOCATION.
[6]	"Expression of retinoic acid-inducible gene-I in vascular smooth muscle cells stimulated with interferon-gamma." Imaizumi T., Yagihashi N., Hatakeyama M., Yamashita K., Ishikawa A., Taima K., Yoshida H., Inoue I., Fujita T., Yagihashi S., Satoh K. Life Sci. 75:1171-1180(2004) [PubMed: 15219805] [Abstract] Cited for: INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[7]	"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses." Yoneyama M., Kikuchi M., Natsukawa T., Shinobu N., Imaizumi T., Miyagishi M., Taira K., Akira S., Fujita T. Nat. Immunol. 5:730-737(2004) [PubMed: 15208624] [Abstract] Cited for: INDUCTION, MUTAGENESIS OF LYS-270, SUBCELLULAR LOCATION, BINDING TO DOUBLE-STRANDED RNA, FUNCTION.
[8]	"Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3." Seth R.B., Sun L., Ea C.-K., Chen Z.J. Cell 122:669-682(2005) [PubMed: 16125763] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS.
[9]	"SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways." Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B. EMBO J. 24:4018-4028(2005) [PubMed: 16281057] [Abstract] Cited for: INTERACTION WITH IKBKE AND TBK1.
[10]	"Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I." Sumpter R. Jr., Loo Y.-M., Foy E., Li K., Yoneyama M., Fujita T., Lemon S.M., Gale M. Jr. J. Virol. 79:2689-2699(2005) [PubMed: 15708988] [Abstract] Cited for: INDUCTION, MUTAGENESIS OF THR-55 AND LYS-270, BINDING TO DOUBLE-STRANDED RNA, FUNCTION.
[11]	"VISA is an adapter protein required for virus-triggered IFN-beta Signaling." Xu L.-G., Wang Y.-Y., Han K.-J., Li L.-Y., Zhai Z., Shu H.-B. Mol. Cell 19:727-740(2005) [PubMed: 16153868] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS.
[12]	"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction." Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S. Nat. Immunol. 6:981-988(2005) [PubMed: 16127453] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS.
[13]	"Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways." Zhao C., Denison C., Huibregtse J.M., Gygi S.P., Krug R.M. Proc. Natl. Acad. Sci. U.S.A. 102:10200-10205(2005) [PubMed: 16009940] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, ISGYLATION.
[14]	"Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2." Saito T., Hirai R., Loo Y.-M., Owen D., Johnson C.L., Sinha S.C., Akira S., Fujita T., Gale M. Jr. Proc. Natl. Acad. Sci. U.S.A. 104:582-587(2007) [PubMed: 17190814] [Abstract] Cited for: FUNCTION, SUBUNIT, REPRESSOR DOMAIN, INTERACTION WITH DHX58.
[15]	"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling." Ishikawa H., Barber G.N. Nature 455:674-678(2008) [PubMed: 18724357] [Abstract] Cited for: INTERACTION WITH TMEM173.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF038963 mRNA. Translation: AAD19826.1.
AL353671, AL161783 Genomic DNA. Translation: CAH71251.1.
AL161783, AL353671 Genomic DNA. Translation: CAH72600.1.
BX647917 mRNA. Translation: CAI46068.1.
AL137608 mRNA. Translation: CAB70840.1.

IPI

IPI00295503.
IPI00654731.

PIR

T46312.

RefSeq

NP_055129.2.

UniGene

Hs.190622

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QFB	X-ray	3.00	A/B/C/D/E/F/G/H/I/J	802-925	[»]
2QFD	X-ray	2.70	A/B/C/D/E/F/G/H/I/J	802-925	[»]
2RMJ	NMR	-	A	792-925	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O95786. 1 interaction.

PTM databases

PhosphoSite

O95786.

Proteomic databases

PRIDE

O95786.

Genome annotation databases

Ensembl

ENSG00000107201. Homo sapiens. [Contig view]

GeneID

23586.

KEGG

hsa:23586.

Organism-specific databases

GeneCards

GC09M032447.

HGNC

HGNC:19102. DDX58.

HPA

CAB012643.

MIM

609631. gene.

PharmGKB

PA134994272.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O95786.

HOVERGEN

O95786.

OMA

O95786. WDFQKIE.

Gene expression databases

ArrayExpress

O95786.

Bgee

O95786.

CleanEx

HS_DDX58.

GermOnline

ENSG00000107201. Homo sapiens.

Family and domain databases

InterPro

IPR003593. ATPase_AAA+_core.
IPR014001. DEAD-like_N.
IPR001650. DNA/RNA_helicase_C.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR014021. Helicase_SF1/SF2_ATP-bd.
[Graphical view]

Pfam

PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]

SMART

SM00382. AAA. 1 hit.
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]

PROSITE

PS50209. CARD. False negative.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

46208.

SOURCE

Search...

Entry information

Entry name

DDX58_HUMAN

Accession

Primary (citable) accession number: O95786
Secondary accession number(s): Q5HYE1, Q5VYT1, Q9NT04

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	November 8, 2005
Last modified:	June 16, 2009
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)