Q96C10 (DHX58_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable ATP-dependent RNA helicase DHX58
EC=3.6.4.13

Alternative name(s):
Probable ATP-dependent helicase LGP2
Protein D11Lgp2 homolog
RIG-I-like receptor 3
Short name=RLR-3
RIG-I-like receptor LGP2
Short name=RLR

Gene names

Name:	DHX58
Synonyms:	D11LGP2E, LGP2

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

General annotation (Comments)

Function	Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate. Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18
Catalytic activity	ATP + H2O = ADP + phosphate.
Cofactor	Zinc.
Subunit structure	Monomer in the absence of dsRNA. Homodimer in the presence of dsRNA. Interacts with DDX58/RIG-I (via CARD domain), MAVS/IPS1 and DDX60. Found in a complex with DDX58/RIG-I and IFIH1/MDA5. Interacts (via helicase C-terminal domain) with non-structural protein V of Human parainfluenza 2 virus, Human parainfluenza 5 virus, measles virus, mumps virus, hendra virus and nipah virus. Ref.4 Ref.5 Ref.7 Ref.9 Ref.13 Ref.16 Ref.18
Subcellular location	Cytoplasm Ref.17.
Induction	By interferon (IFN), virus infection, or intracellular dsRNA.
Domain	The repressor domain is capable of inhibiting dimerization and signaling of DDX58/RIG-I and also facilitates binding of dsRNA.
Sequence similarities	Belongs to the helicase family. RLR subfamily. 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	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding Zinc
Molecular function	Helicase Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of MDA-5 signaling pathway Inferred from mutant phenotype Ref.11. Source: UniProtKB negative regulation of RIG-I signaling pathway Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of innate immune response Inferred from direct assay Ref.12. Source: UniProtKB negative regulation of type I interferon production Inferred from direct assay Ref.12. Source: UniProtKB positive regulation of MDA-5 signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of RIG-I signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of type I interferon production Inferred from sequence or structural similarity. Source: UniProtKB response to virus Inferred from sequence or structural similarity. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: InterPro double-stranded RNA binding Inferred from direct assay Ref.7. Source: UniProtKB helicase activity Inferred from electronic annotation. Source: UniProtKB-KW single-stranded RNA binding Inferred from direct assay Ref.7. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DHX30	Q7L2E3	2	EBI-744193,EBI-1211456
DICER1	Q9UPY3	2	EBI-744193,EBI-395506
EIF2AK2	P19525	2	EBI-744193,EBI-640775
EIF2C2	Q9UKV8	2	EBI-744193,EBI-528269
EIF6	P56537	2	EBI-744193,EBI-372243
NKRF	O15226	2	EBI-744193,EBI-766011
STAU2	Q9NUL3	2	EBI-744193,EBI-722938

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 678

678

Probable ATP-dependent RNA helicase DHX58

PRO_0000102010

Regions

Domain

11 – 188

178

Helicase ATP-binding

Domain

350 – 514

165

Helicase C-terminal

Nucleotide binding

24 – 31

8

ATP Potential

Region

476 – 678

203

Repressor domain

Region

572 – 655

84

RNA-binding

Coiled coil

489 – 546

58

Potential

Motif

131 – 134

4

DECH box

Sites

Metal binding

556

1

Zinc

Metal binding

559

1

Zinc

Metal binding

612

1

Zinc

Metal binding

615

1

Zinc

Natural variations

Natural variant

76

1

T → A.
Corresponds to variant rs34891485 [ dbSNP | Ensembl ].

VAR_049336

Natural variant

95

1

R → Q.
Corresponds to variant rs35118457 [ dbSNP | Ensembl ].

VAR_049337

Natural variant

425

1

Q → R.
Corresponds to variant rs2074158 [ dbSNP | Ensembl ].

VAR_019394

Natural variant

523

1

R → Q.
Corresponds to variant rs2074160 [ dbSNP | Ensembl ].

VAR_019395

Experimental info

Mutagenesis

634

1

K → E: Abolishes RNA binding. Ref.16 Ref.18

Mutagenesis

651

1

K → E: Abolishes RNA binding. Ref.16

Sequence conflict

473

1

R → W in BAB13818. Ref.1

Secondary structure

1

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678

Helix Strand Turn

Details...

Helix

549 – 551

3

Beta strand

553 – 556

4

Turn

557 – 559

3

Beta strand

562 – 565

4

Helix

566 – 568

3

Beta strand

569 – 572

4

Turn

573 – 575

3

Beta strand

576 – 579

4

Helix

582 – 587

6

Beta strand

588 – 590

3

Beta strand

592 – 594

3

Beta strand

597 – 599

3

Beta strand

602 – 612

11

Turn

613 – 615

3

Beta strand

618 – 625

8

Beta strand

628 – 633

6

Helix

635 – 637

3

Beta strand

638 – 642

5

Beta strand

645 – 647

3

Helix

652 – 654

3

Beta strand

655 – 657

3

Helix

664 – 671

8

Sequences

	Sequence		Length	Mass (Da)
	Q96C10 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 859E1749C7313D06	FASTA	678	76,613
	10 20 30 40 50 60 MELRSYQWEV IMPALEGKNI IIWLPTGAGK TRAAAYVAKR HLETVDGAKV VVLVNRVHLV 70 80 90 100 110 120 TQHGEEFRRM LDGRWTVTTL SGDMGPRAGF GHLARCHDLL ICTAELLQMA LTSPEEEEHV 130 140 150 160 170 180 ELTVFSLIVV DECHHTHKDT VYNVIMSQYL ELKLQRAQPL PQVLGLTASP GTGGASKLDG 190 200 210 220 230 240 AINHVLQLCA NLDTWCIMSP QNCCPQLQEH SQQPCKQYNL CHRRSQDPFG DLLKKLMDQI 250 260 270 280 290 300 HDHLEMPELS RKFGTQMYEQ QVVKLSEAAA LAGLQEQRVY ALHLRRYNDA LLIHDTVRAV 310 320 330 340 350 360 DALAALQDFY HREHVTKTQI LCAERRLLAL FDDRKNELAH LATHGPENPK LEMLEKILQR 370 380 390 400 410 420 QFSSSNSPRG IIFTRTRQSA HSLLLWLQQQ QGLQTVDIRA QLLIGAGNSS QSTHMTQRDQ 430 440 450 460 470 480 QEVIQKFQDG TLNLLVATSV AEEGLDIPHC NVVVRYGLLT NEISMVQARG RARADQSVYA 490 500 510 520 530 540 FVATEGSREL KRELINEALE TLMEQAVAAV QKMDQAEYQA KIRDLQQAAL TKRAAQAAQR 550 560 570 580 590 600 ENQRQQFPVE HVQLLCINCM VAVGHGSDLR KVEGTHHVNV NPNFSNYYNV SRDPVVINKV 610 620 630 640 650 660 FKDWKPGGVI SCRNCGEVWG LQMIYKSVKL PVLKVRSMLL ETPQGRIQAK KWSRVPFSVP 670 DFDFLQHCAE NLSDLSLD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: Embryo.
[2]	"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: Colon.
[3]	"Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity." Yoneyama M., Kikuchi M., Matsumoto K., Imaizumi T., Miyagishi M., Taira K., Foy E., Loo Y.-M., Gale M. Jr., Akira S., Yonehara S., Kato A., Fujita T. J. Immunol. 175:2851-2858(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2." Komuro A., Horvath C.M. J. Virol. 80:12332-12342(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1 AND DDX58/RIG-I.
[5]	"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, INTERACTION WITH DDX58/RIG-I.
[6]	"Regulation of interferon production by RIG-I and LGP2: a lesson in self-control." Vitour D., Meurs E.F. Sci. STKE 2007:PE20-PE20(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[7]	"Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response." Murali A., Li X., Ranjith-Kumar C.T., Bhardwaj K., Holzenburg A., Li P., Kao C.C. J. Biol. Chem. 283:15825-15833(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT.
[8]	"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.
[9]	"A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2." Parisien J.P., Bamming D., Komuro A., Ramachandran A., Rodriguez J.J., Barber G., Wojahn R.D., Horvath C.M. J. Virol. 83:7252-7260(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARAMYXOVIRUSES NON-STRUCTURAL PROTEIN V.
[10]	"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.
[11]	"RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium." Broquet A.H., Hirata Y., McAllister C.S., Kagnoff M.F. J. Immunol. 186:1618-1626(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Ambivalent role of the innate immune response in rabies virus pathogenesis." Chopy D., Pothlichet J., Lafage M., Megret F., Fiette L., Si-Tahar M., Lafon M. J. Virol. 85:6657-6668(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"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.
[14]	"Regulation of RLR-mediated innate immune signaling--it is all about keeping the balance." Eisenaecher K., Krug A. Eur. J. Cell Biol. 91:36-47(2012) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[15]	"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.
[16]	"The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA." Li X., Ranjith-Kumar C.T., Brooks M.T., Dharmaiah S., Herr A.B., Kao C., Li P. J. Biol. Chem. 284:13881-13891(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 541-678 IN COMPLEX WITH RNA, FUNCTION, SUBUNIT, MUTAGENESIS OF LYS-634 AND LYS-651, ZINC-BINDING SITES.
[17]	"Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors." Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F. J. Biol. Chem. 284:17465-17474(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 546-678, FUNCTION, SUBCELLULAR LOCATION.
[18]	"The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA." Pippig D.A., Hellmuth J.C., Cui S., Kirchhofer A., Lammens K., Lammens A., Schmidt A., Rothenfusser S., Hopfner K.-P. Nucleic Acids Res. 37:2014-2025(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 537-678, FUNCTION, SUBUNIT, MUTAGENESIS OF LYS-634, ZINC-BINDING SITES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK021416 mRNA. Translation: BAB13818.1.
BC014949 mRNA. Translation: AAH14949.1.

IPI

IPI00303746.

RefSeq

NP_077024.2. NM_024119.2.

UniGene

Hs.55918.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RQA	NMR	-	A	546-678	[»]
2W4R	X-ray	2.60	A/B/C/D	537-678	[»]
3EQT	X-ray	2.00	A/B	541-678	[»]

ProteinModelPortal

Q96C10.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96C10. 12 interactions.

MINT

MINT-1460040.

STRING

9606.ENSP00000251642.

PTM databases

PhosphoSite

Q96C10.

Polymorphism databases

DMDM

50401123.

Proteomic databases

PaxDb

Q96C10.

PRIDE

Q96C10.

Protocols and materials databases

DNASU

79132.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000251642; ENSP00000251642; ENSG00000108771.
ENST00000563880; ENSP00000455290; ENSG00000260178.

GeneID

79132.

KEGG

hsa:79132.

UCSC

uc002hyw.3. human.

Organism-specific databases

CTD

79132.

GeneCards

GC17M040255.

HGNC

HGNC:29517. DHX58.

HPA

HPA018670.
HPA019570.

MIM

608588. gene.

neXtProt

NX_Q96C10.

PharmGKB

PA162383566.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1111.

HOGENOM

HOG000230992.

HOVERGEN

HBG106019.

InParanoid

Q96C10.

KO

K12649.

OMA

ELRPYQW.

OrthoDB

EOG44QT15.

Gene expression databases

ArrayExpress

Q96C10.

Bgee

Q96C10.

CleanEx

HS_DHX58.

Genevestigator

Q96C10.

GermOnline

ENSG00000108771. Homo sapiens.

Family and domain databases

InterPro

IPR006935. Helicase/UvrB_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR021673. RIG-I_C-RD.
[Graphical view]

Pfam

PF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]

SMART

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

PROSITE

PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DHX58. human.

EvolutionaryTrace

Q96C10.

GenomeRNAi

79132.

NextBio

67993.

SOURCE

Search...

Entry information

Entry name

DHX58_HUMAN

Accession

Primary (citable) accession number: Q96C10
Secondary accession number(s): Q9HAM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 94 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.