O95786 (DDX58_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable ATP-dependent RNA helicase DDX58
EC=3.6.4.13

Alternative name(s):
DEAD box protein 58
RIG-I-like receptor 1
Short name=RLR-1
Retinoic acid-inducible gene 1 protein
Short name=RIG-1
Retinoic acid-inducible gene I protein
Short name=RIG-I

Gene names

Name:

DDX58

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

General annotation (Comments)

Function	Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.17 Ref.18 Ref.20 Ref.21 Ref.23 Ref.24 Ref.27 Ref.37
Catalytic activity	ATP + H2O = ADP + phosphate.
Cofactor	Zinc.
Subunit structure	Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts with MAVS/IPS1. Interacts with DHX58/LGP2, IKBKE, TBK1 and TMEM173/STING. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts with RNF135. Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to DDX58. Interacts with SRC. Interacts with protein Z of Guanarito virus, Machupo virus, Junin arenavirus and Sabia virus. This interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction. Interacts (via CARD domain) with Human respiratory syncytial virus A non-structural protein 2 (NS2) and this interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 activation. Interacts with Rotavirus A non-structural protein 1 (NSP1) and this interaction induces down-regulation of DDX58/RIG-I. Interacts with DDX60. Interacts with isoform 2 of ZC3HAV1 (via zinc-fingers) in an RNA-dependent manner. Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.30 Ref.33 Ref.38 Ref.41 Ref.42 Ref.43
Subcellular location	Cytoplasm. Cell projection › ruffle membrane. Cytoplasm › cytoskeleton. Cell junction › tight junction. Note: Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles. Ref.7 Ref.8 Ref.9 Ref.16 Ref.23 Ref.42
Tissue specificity	Present in vascular smooth cells (at protein level). Ref.8
Induction	By bacterial lipopolysaccharides (LPS) in endothelial cells. By interferon (IFN). Ref.2 Ref.7 Ref.8 Ref.9 Ref.12
Domain	The repressor domain controls homomultimerization and interaction with MAVS/IPS1. In the absence of viral infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through intramolecular interactions mediated by the repressor domain. Upon binding to viral RNA in the presence of ATP, the repressor domain induces a conformational change exposing the CARD domain and promotes dimerization and CARD interactions with the adapter protein MAVS/IPS1 leading to the induction of downstream signaling. Ref.17 The helicase domain is responsible for dsRNA recognition. Ref.17 The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton. Ref.17 The second CARD domain is the primary site for 'Lys-63'-linked ubiquitination. Ref.17
Post-translational modification	Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation. Ref.40 Isgylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. Ubiquitinated. Undergoes 'Lys-48'- and 'Lys-63'-linked ubiquitination. Lys-172 is the critical site for TRIM25-mediated ubiquitination, for MAVS/IPS1 binding and to induce anti-viral signal transduction. Lys-154, Lys-164 and Lys-172 are critical sites for RNF135-mediated ubiquitination. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'-and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor. Ref.16 Ref.18 Ref.22 Ref.28 Ref.31
Sequence similarities	Belongs to the helicase family. RLR subfamily. Contains 2 CARD domains. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	Antiviral defense Host-virus interaction Immunity Innate immunity
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Tight junction
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding Zinc
Molecular function	Helicase Hydrolase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RIG-I signaling pathway Inferred from mutant phenotype Ref.24. Source: UniProtKB detection of virus Inferred from direct assay PubMed 17079289. Source: BHF-UCL innate immune response Inferred from mutant phenotype Ref.27Ref.20. Source: UniProtKB negative regulation of type I interferon production Traceable author statement. Source: Reactome positive regulation of defense response to virus by host Inferred from mutant phenotype Ref.27. Source: UniProtKB positive regulation of interferon-alpha production Inferred from direct assay Ref.21. Source: UniProtKB positive regulation of interferon-beta production Inferred from mutant phenotype Ref.24Ref.27Ref.20. Source: UniProtKB positive regulation of sequence-specific DNA binding transcription factor activity Inferred by curator PubMed 17079289. Source: BHF-UCL positive regulation of transcription factor import into nucleus Inferred from direct assay PubMed 17079289. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17079289. Source: BHF-UCL regulation of cell migration Inferred from direct assay Ref.23. Source: UniProtKB regulation of type III interferon production Traceable author statement Ref.35. Source: UniProtKB response to exogenous dsRNA Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	actin cytoskeleton Inferred from direct assay Ref.23. Source: UniProtKB cytosol Traceable author statement. Source: Reactome ruffle membrane Inferred from direct assay Ref.23. Source: UniProtKB tight junction Inferred from direct assay Ref.23. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro double-stranded DNA binding Inferred from electronic annotation. Source: Compara double-stranded RNA binding Inferred from direct assay Ref.21. Source: UniProtKB single-stranded RNA binding Inferred from mutant phenotype Ref.24. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.45. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-995350,EBI-995350
1B	P04543	2	EBI-995350,EBI-3648048	From a different organism.
Casp12	Q920D5	4	EBI-995350,EBI-1374296	From a different organism.
DDX3X	O00571	2	EBI-995350,EBI-353779
MAVS	Q7Z434	8	EBI-995350,EBI-995373
WRNIP1	Q96S55	2	EBI-995350,EBI-2513471
Z	Q6IUF9	3	EBI-995350,EBI-3647473	From a different organism.
Z	Q6IVU5	3	EBI-995350,EBI-3647294	From a different organism.
Z	Q6UY62	2	EBI-995350,EBI-3647496	From a different organism.
Z	Q6UY71	3	EBI-995350,EBI-3647448	From a different organism.
ZC3HAV1	Q7Z2W4	3	EBI-995350,EBI-922540
ZC3HAV1	Q7Z2W4-2	4	EBI-995350,EBI-922559

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

218 – 925

708

Interaction with ZC3HAV1

Region

735 – 925

191

Repressor domain

Motif

372 – 375

4

DECH box

Sites

Metal binding

810

1

Zinc

Metal binding

813

1

Zinc

Metal binding

864

1

Zinc

Metal binding

869

1

Zinc

Amino acid modifications

Modified residue

770

1

Phosphothreonine; by CK2 Ref.40

Modified residue

854

1

Phosphoserine; by CK2 Ref.40

Modified residue

855

1

Phosphoserine; by CK2 Ref.40

Modified residue

858

1

N6-acetyllysine Ref.29

Cross-link

154

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Cross-link

164

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Cross-link

172

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Alternative sequence

36 – 80

45

Missing in isoform 2.

VSP_016054

Natural variant

7

1

R → C. Ref.6
Corresponds to variant rs10813831 [ dbSNP | Ensembl ].

VAR_023747

Natural variant

580

1

D → E. Ref.1 Ref.2
Corresponds to variant rs17217280 [ dbSNP | Ensembl ].

VAR_023748

Experimental info

Mutagenesis

55

1

T → I: No IRF3 signaling activity; no effect on dsRNA binding. Ref.12

Mutagenesis

99

1

K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16

Mutagenesis

154

1

K → R: Reduction of ubiquitination. Reduction of INFB induction. Ref.28

Mutagenesis

164

1

K → R: Reduction of ubiquitination. Reduction of INFB induction. Ref.28

Mutagenesis

169

1

K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16

Mutagenesis

172

1

K → R: Complete loss of ubiquitination; No interaction with MAVS/IPS1; No induction of IFN-beta. Ref.16 Ref.28

Mutagenesis

181

1

K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16

Mutagenesis

190

1

K → R: Little or no effect on ubiquitination of the 2 CARD domains.

Mutagenesis

193

1

K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16

Mutagenesis

270

1

K → A: No IRF3 signaling activity. Ref.9 Ref.12

Secondary structure

1

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925

Helix Strand Turn

Details...

Helix

97 – 109

13

Helix

111 – 117

7

Turn

120 – 123

4

Helix

124 – 127

4

Turn

128 – 130

3

Helix

133 – 145

13

Helix

148 – 161

14

Helix

166 – 178

13

Helix

182 – 185

4

Helix

245 – 255

11

Beta strand

260 – 263

4

Helix

270 – 284

15

Beta strand

293 – 296

4

Helix

300 – 313

14

Turn

314 – 318

5

Beta strand

321 – 324

4

Beta strand

326 – 328

3

Beta strand

330 – 332

3

Helix

334 – 339

6

Beta strand

342 – 346

5

Helix

348 – 356

9

Helix

363 – 365

3

Beta strand

367 – 372

6

Helix

374 – 376

3

Beta strand

377 – 381

5

Helix

382 – 395

14

Beta strand

404 – 410

7

Helix

420 – 433

14

Beta strand

438 – 440

3

Helix

446 – 452

7

Beta strand

457 – 462

6

Helix

470 – 489

20

Helix

493 – 495

3

Beta strand

496 – 498

3

Beta strand

504 – 506

3

Helix

507 – 518

12

Helix

519 – 521

3

Helix

531 – 557

27

Helix

560 – 575

16

Helix

581 – 591

11

Helix

594 – 602

9

Helix

604 – 606

3

Helix

609 – 622

14

Beta strand

630 – 633

4

Helix

637 – 649

13

Helix

651 – 653

3

Beta strand

658 – 660

3

Beta strand

668 – 670

3

Helix

675 – 683

9

Beta strand

694 – 700

7

Beta strand

710 – 716

7

Helix

721 – 727

7

Beta strand

737 – 743

7

Helix

745 – 768

24

Helix

773 – 793

21

Beta strand

801 – 804

4

Beta strand

806 – 810

5

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 – 839

4

Beta strand

842 – 846

5

Beta strand

856 – 864

9

Turn

867 – 869

3

Beta strand

872 – 879

8

Beta strand

882 – 887

6

Helix

889 – 891

3

Beta strand

892 – 896

5

Turn

897 – 899

3

Beta strand

902 – 904

3

Turn

908 – 910

3

Helix

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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[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] (ISOFORM 1). Tissue: Brain.
[6]	"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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [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.
[7]	"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] [Europe PMC] [Abstract] Cited for: INDUCTION, SUBCELLULAR LOCATION.
[8]	"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] [Europe PMC] [Abstract] Cited for: INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]	"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] [Europe PMC] [Abstract] Cited for: INDUCTION, MUTAGENESIS OF LYS-270, SUBCELLULAR LOCATION, BINDING TO DOUBLE-STRANDED RNA, FUNCTION.
[10]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IKBKE AND TBK1.
[12]	"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] [Europe PMC] [Abstract] Cited for: INDUCTION, MUTAGENESIS OF THR-55 AND LYS-270, BINDING TO DOUBLE-STRANDED RNA, FUNCTION.
[13]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1.
[14]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1.
[15]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, ISGYLATION.
[16]	"TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity." Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O., Akira S., Chen Z., Inoue S., Jung J.U. Nature 446:916-920(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRIM25, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF LYS-99; LYS-169; LYS-172; LYS-181 AND LYS-193.
[17]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, REPRESSOR DOMAIN, INTERACTION WITH DHX58.
[18]	"The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response." Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A., Cardenas W.B., Yount J.S., Moran T.M., Basler C.F., Komuro A., Horvath C.M., Xavier R., Ting A.T. EMBO Rep. 9:930-936(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, UBIQUITINATION, INTERACTION WITH CYLD.
[19]	"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling." Ishikawa H., Barber G.N. Nature 455:674-678(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TMEM173.
[20]	"RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway." Chiu Y.-H., Macmillan J.B., Chen Z.J. Cell 138:576-591(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus." Schlee M., Roth A., Hornung V., Hagmann C.A., Wimmenauer V., Barchet W., Coch C., Janke M., Mihailovic A., Wardle G., Juranek S., Kato H., Kawai T., Poeck H., Fitzgerald K.A., Takeuchi O., Akira S., Tuschl T. , Latz E., Ludwig J., Hartmann G. Immunity 31:25-34(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[22]	"Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection." Oshiumi H., Matsumoto M., Hatakeyama S., Seya T. J. Biol. Chem. 284:807-817(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH RNF135.
[23]	"Retinoic acid-induced gene-1 (RIG-I) associates with the actin cytoskeleton via caspase activation and recruitment domain-dependent interactions." Mukherjee A., Morosky S.A., Shen L., Weber C.R., Turner J.R., Kim K.S., Wang T., Coyne C.B. J. Biol. Chem. 284:6486-6494(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[24]	"Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2." Bamming D., Horvath C.M. J. Biol. Chem. 284:9700-9712(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[25]	"The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling." Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W. J. Biol. Chem. 284:19122-19131(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SRC.
[26]	"Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I." Ling Z., Tran K.C., Teng M.N. J. Virol. 83:3734-3742(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HRSV PROTEIN NS2.
[27]	"RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate." Ablasser A., Bauernfeind F., Hartmann G., Latz E., Fitzgerald K.A., Hornung V. Nat. Immunol. 10:1065-1072(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[28]	"REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I." Gao D., Yang Y.K., Wang R.P., Zhou X., Diao F.C., Li M.D., Zhai Z.H., Jiang Z.F., Chen D.Y. PLoS ONE 4:E5760-E5760(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-154; LYS-164 AND LYS-172, INTERACTION WITH RNF135, MUTAGENESIS OF LYS-154; LYS-164 AND LYS-172.
[29]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-858, MASS SPECTROMETRY.
[30]	"NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways." Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., Zheng S., Chen Z.J., Wang R.F. Cell 141:483-496(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NLRC5.
[31]	"The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling." Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B. Cell Res. 20:802-811(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP17L2.
[32]	"Function and regulation of retinoic acid-inducible gene-I." Matsumiya T., Stafforini D.M. Crit. Rev. Immunol. 30:489-513(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[33]	"Z proteins of New World arenaviruses bind RIG-I and interfere with type I interferon induction." Fan L., Briese T., Lipkin W.I. J. Virol. 84:1785-1791(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEW WORLD ARENAVIRUSES PROTEIN Z.
[34]	"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].
[35]	"Immune signaling by RIG-I-like receptors." Loo Y.M., Gale M. Jr. Immunity 34:680-692(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[36]	"RIG-I-like receptors: cytoplasmic sensors for non-self RNA." Kato H., Takahasi K., Fujita T. Immunol. Rev. 243:91-98(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[37]	"Innate immune responses in human monocyte-derived dendritic cells are highly dependent on the size and the 5' phosphorylation of RNA molecules." Jiang M., Osterlund P., Sarin L.P., Poranen M.M., Bamford D.H., Guo D., Julkunen I. J. Immunol. 187:1713-1721(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[38]	"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: INTERACTION WITH IFIT3.
[39]	"Retinoic acid-inducible gene-I-like receptors." Onoguchi K., Yoneyama M., Fujita T. J. Interferon Cytokine Res. 31:27-31(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[40]	"Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response." Sun Z., Ren H., Liu Y., Teeling J.L., Gu J. J. Virol. 85:1036-1047(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-770; SER-854 AND SER-855.
[41]	"DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling." Miyashita M., Oshiumi H., Matsumoto M., Seya T. Mol. Cell. Biol. 31:3802-3819(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DDX60.
[42]	"ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses." Hayakawa S., Shiratori S., Yamato H., Kameyama T., Kitatsuji C., Kashigi F., Goto S., Kameoka S., Fujikura D., Yamada T., Mizutani T., Kazumata M., Sato M., Tanaka J., Asaka M., Ohba Y., Miyazaki T., Imamura M., Takaoka A. Nat. Immunol. 12:37-44(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZC3HAV1, SUBCELLULAR LOCATION.
[43]	"Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I." Qin L., Ren L., Zhou Z., Lei X., Chen L., Xue Q., Liu X., Wang J., Hung T. Virol. J. 8:526-526(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ROTAVIRUS PROTEIN NSP1.
[44]	"Sensing of viral nucleic acids by RIG-I: from translocation to translation." Schmidt A., Rothenfusser S., Hopfner K.P. Eur. J. Cell Biol. 91:78-85(2012) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[45]	"The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I." Cui S., Eisenaecher K., Kirchhofer A., Brzozka K., Lammens A., Lammens K., Fujita T., Conzelmann K.-K., Krug A., Hopfner K.-P. Mol. Cell 29:169-179(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 802-925 IN COMPLEX WITH ZINC IONS.
[46]	"Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses." Takahasi K., Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita R., Gale M. Jr., Inagaki F., Fujita T. Mol. Cell 29:428-440(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 792-925.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF038963 mRNA. Translation: AAD19826.1.
AL353671, AL161783 Genomic DNA. Translation: CAH71251.1.
AL161783, AL353671 Genomic DNA. Translation: CAH72600.1.
CH471071 Genomic DNA. Translation: EAW58548.1.
BC132786 mRNA. Translation: AAI32787.1.
BC136610 mRNA. Translation: AAI36611.1.
BX647917 mRNA. Translation: CAI46068.1.
AL137608 mRNA. Translation: CAB70840.1.

IPI

IPI00295503.
IPI00654731.

PIR

T46312.

RefSeq

NP_055129.2. NM_014314.3.

UniGene

Hs.190622.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LWD	NMR	-	A	95-190	[»]
2LWE	NMR	-	A	95-190	[»]
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	[»]
2YKG	X-ray	2.50	A	230-925	[»]
3LRN	X-ray	2.60	A/B	803-923	[»]
3LRR	X-ray	2.15	A/B	803-923	[»]
3NCU	X-ray	2.55	A/B	792-925	[»]
3OG8	X-ray	2.40	A/B	802-925	[»]
3TMI	X-ray	2.90	A	232-925	[»]
4AY2	X-ray	2.80	A	239-925	[»]

ProteinModelPortal

O95786.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35444N.

IntAct

O95786. 12 interactions.

MINT

MINT-2799116.

STRING

9606.ENSP00000369213.

PTM databases

PhosphoSite

O95786.

Proteomic databases

PaxDb

O95786.

PRIDE

O95786.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379882; ENSP00000369212; ENSG00000107201.
ENST00000379883; ENSP00000369213; ENSG00000107201.

GeneID

23586.

KEGG

hsa:23586.

UCSC

uc003zra.3. human.
uc010mjk.1. human.

Organism-specific databases

CTD

23586.

GeneCards

GC09M032447.

HGNC

HGNC:19102. DDX58.

HPA

CAB012643.

MIM

609631. gene.

neXtProt

NX_O95786.

PharmGKB

PA134994272.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1111.

HOGENOM

HOG000230911.

HOVERGEN

HBG052325.

InParanoid

O95786.

KO

K12646.

OMA

KCKAFAC.

OrthoDB

EOG4SQWW0.

PhylomeDB

O95786.

Enzyme and pathway databases

Reactome

REACT_107772. Immune System.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O95786.

Bgee

O95786.

CleanEx

HS_DDX58.

Genevestigator

O95786.

GermOnline

ENSG00000107201. Homo sapiens.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.

InterPro

IPR003593. AAA+_ATPase.
IPR011029. DEATH-like_dom.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR021673. RIG-I_C-RD.
[Graphical view]

Pfam

PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
PF11648. RIG-I_C-RD. 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

ChiTaRS

DDX58. human.

EvolutionaryTrace

O95786.

GenomeRNAi

23586.

NextBio

46208.

SOURCE

Search...

Entry information

Entry name

DDX58_HUMAN

Accession

Primary (citable) accession number: O95786
Secondary accession number(s): A2RU81 , Q5HYE1, Q5VYT1, Q9NT04

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	November 8, 2005
Last modified:	May 1, 2013
This is version 111 of the entry and version 2 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.