Dhx58

Functionⁱ

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.4 Publications

Catalytic activityⁱ

ATP + H₂O = ADP + phosphate.

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	556	ZincPROSITE-ProRule annotation	1
Metal bindingⁱ	559	ZincPROSITE-ProRule annotation	1
Metal bindingⁱ	612	ZincPROSITE-ProRule annotation	1
Metal bindingⁱ	615	ZincPROSITE-ProRule annotation	1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	24 – 31	ATPPROSITE-ProRule annotation		8

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
DNA binding Source: InterPro
double-stranded RNA binding
Source: MGI
Inferred from direct assayⁱ
- 21703541
helicase activity Source: UniProtKB-KW
single-stranded RNA binding Source: UniProtKB
zinc ion binding Source: UniProtKB

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

defense response to virus Source: UniProtKB-KW
innate immune response Source: UniProtKB-KW
negative regulation of innate immune response
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 21525357
negative regulation of MDA-5 signaling pathway Source: UniProtKB
negative regulation of RIG-I signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 17475874
negative regulation of type I interferon production
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 21525357
positive regulation of MDA-5 signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20080593
positive regulation of RIG-I signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20080593
positive regulation of type I interferon production
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20080593
regulation of innate immune response Source: MGI
response to bacterium
Source: MGI
Inferred from expression patternⁱ
- 23012479
response to virus
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20080593

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Helicase, Hydrolase, RNA-binding
Biological process	Antiviral defense, Immunity, Innate immunity
Ligand	ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Probable ATP-dependent RNA helicase DHX58 (EC:3.6.4.13) Alternative name(s): Probable ATP-dependent helicase LGP2 Protein D11Lgp2 RIG-I-like receptor 3 Short name: RLR-3 RIG-I-like receptor Lgp2 Short name: RLR
Gene namesⁱ	Name:Dhx58 Synonyms:D11lgp2e, Lgp2
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 11

Organism-specific databases

MGIⁱ	MGI:1931560 Dhx58

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Disruption phenotypeⁱ

Embryonic lethality at a high frequency. Adult female that survive show an enlarged uterus filled with fluid resulting from vaginal atresia.1 Publication

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	30	K → A: Abolishes IFNB1 production upon infection with various viruses. 1 Publication		1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000102011	1 – 678	Probable ATP-dependent RNA helicase DHX58Add BLAST		678

Proteomic databases

EPDⁱ	Q99J87
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q99J87
PaxDbⁱ	Q99J87
PRIDEⁱ	Q99J87

PTM databases

iPTMnetⁱ	Q99J87
PhosphoSitePlusⁱ	Q99J87

Expressionⁱ

Tissue specificityⁱ

Highly expressed in mammary tissues. Expressed in liver and testis. Expressed at lower level in spleen, embryo, mammary gland and breast tumors.1 Publication

Inductionⁱ

By interferon (IFN), virus infection, or intracellular dsRNA.

Gene expression databases

Bgeeⁱ	ENSMUSG00000017830 Expressed in 107 organ(s), highest expression level in bone marrow macrophage
CleanExⁱ	MM_DHX58
Genevisibleⁱ	Q99J87 MM

Interactionⁱ

Subunit structureⁱ

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 with ANKRD17. Directly interacts with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates (By similarity).By similarity

Protein-protein interaction databases

BioGridⁱ	219822, 1 interactor
STRINGⁱ	10090.ENSMUSP00000017974

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q99J87
SMRⁱ	Q99J87
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	11 – 188	Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST	178
Domainⁱ	353 – 514	Helicase C-terminalPROSITE-ProRule annotationAdd BLAST	162
Domainⁱ	542 – 669	RLR CTRPROSITE-ProRule annotationAdd BLAST	128

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	572 – 655	RNA-bindingBy similarityAdd BLAST		84

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	489 – 546	Sequence analysisAdd BLAST		58

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	131 – 134	DECH box		4

Domainⁱ

The RLR CTR domain is capable of inhibiting dimerization and signaling of DDX58/RIG-I and also facilitates binding of dsRNA.

Sequence similaritiesⁱ

Belongs to the helicase family. RLR subfamily.Curated

Keywords - Domainⁱ

Coiled coil

Phylogenomic databases

eggNOGⁱ	KOG0354 Eukaryota COG1111 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00510000046789
HOGENOMⁱ	HOG000230992
HOVERGENⁱ	HBG106019
InParanoidⁱ	Q99J87
KEGG Orthology (KO) More...KOⁱ	K12649
OMAⁱ	HRAVGNY
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G01PQ
TreeFamⁱ	TF330258

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00079 HELICc, 1 hit
Gene3Dⁱ	2.170.150.30, 1 hit
InterProⁱ	View protein in InterPro IPR006935 Helicase/UvrB_N IPR014001 Helicase_ATP-bd IPR001650 Helicase_C IPR027417 P-loop_NTPase IPR038557 RLR_C_sf IPR021673 RLR_CTR
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00271 Helicase_C, 1 hit PF04851 ResIII, 1 hit PF11648 RIG-I_C-RD, 1 hit
SMARTⁱ	View protein in SMART SM00487 DEXDc, 1 hit SM00490 HELICc, 1 hit
SUPFAMⁱ	SSF52540 SSF52540, 1 hit
PROSITEⁱ	View protein in PROSITE PS51192 HELICASE_ATP_BIND_1, 1 hit PS51194 HELICASE_CTER, 1 hit PS51789 RLR_CTR, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q99J87-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MELRPYQWEV ILPALEGKNI IIWLPTGAGK TRAAAFVAKR HLETVDRGKV 
        60         70         80         90        100
VVLVNRVHLV SQHAEEFRRM LDKHWTVTTL SGDMGSRAGF GLMARSHDLL 
       110        120        130        140        150
ICTAELLQLA LNSSEEDEHV ELREFSLIVV DECHHTHKDT VYNTILSRYL 
       160        170        180        190        200
EQKLKKAEPL PQVLGLTASP GTGGATKLQG AIDHILQLCA NLDTCHIMSP 
       210        220        230        240        250
KNCYSQLLMH NPKPCKQYDL CQRRAQDPFG DLIKKLMNQI HQQLEMPDLK 
       260        270        280        290        300
QQFGTQMYEQ QVVQLCKDAA EAGLQEQRVY ALHLRRYNDA LFIHDTVRAR 
       310        320        330        340        350
DALDMLQDFY DRERTTKTQM VRAESWLLKL FDDHKNVLGQ LAARGPENPK 
       360        370        380        390        400
LEMLERILLK QFGSPGHTRG IIFTRTRQTA SSLLLWLRQQ PCLQTVGIKP 
       410        420        430        440        450
QMLIGAGNTS QSTHMTQKDQ QEVIQEFRDG ILSLLVATSV AEEGLDIAQC 
       460        470        480        490        500
NVVVRYGLLT NEISMVQARG RARAGQSVYS FLATEGSREM KRELTNEALE 
       510        520        530        540        550
VLMEKAVAAV QKMDPDEFKA KIRDLQQASL VKRAARAAHR EIQQGQFLPE 
       560        570        580        590        600
HVQLLCINCM VAVGYGSDLR KVEGTHHVNV NPNFSVYYTT SQNPVVINKV 
       610        620        630        640        650
FKDWRPGGTI RCSNCGEVWG FQMIYKSVTL PVLKIGSILL ETPRGKIQAK 
       660        670 
KWSRVPFSIP VFDILQDCTQ SLSELSLD

Length:678

Mass (Da):76,709

Last modified:July 27, 2011 - v2

Checksum:ⁱD907A30E3AD376A8

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	638	I → M in AAK15474 (PubMed:11161808).Curated	1
Sequence conflictⁱ	638	I → M in AAK15475 (PubMed:11161808).Curated	1
Sequence conflictⁱ	638	I → M in AAH29209 (PubMed:15489334).Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF316999 mRNA Translation: AAK15474.1 AF317000 Genomic DNA Translation: AAK15475.1 AL591469 Genomic DNA Translation: CAM22908.1 BC029209 mRNA Translation: AAH29209.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS25431.1
NCBI Reference Sequences More...RefSeqⁱ	NP_084426.2, NM_030150.2
UniGeneⁱ	Mm.271830

Genome annotation databases

Ensemblⁱ	ENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830
GeneIDⁱ	80861
KEGGⁱ	mmu:80861
UCSC genome browser More...UCSCⁱ	uc007llx.1 mouse

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q99J87	DEXH-box helicase 58		RAT		678	UniRef90_Q99J87
Uncharacterized protein		MOUSE		672
UPI000A30CB84		MUSPA		678
UPI000A317407		MUSCR		678

Protein	Similar proteins		Species	Score	Length	Source
Q99J87	DEXH-box helicase 58		RAT		678	UniRef50_Q99J87
Uncharacterized protein		MOUSE		672
Uncharacterized protein		PROCO		678
Uncharacterized protein		CAVPO		678
DExH-box helicase 58		HORSE		678
+165

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF316999 mRNA Translation: AAK15474.1 AF317000 Genomic DNA Translation: AAK15475.1 AL591469 Genomic DNA Translation: CAM22908.1 BC029209 mRNA Translation: AAH29209.1
CCDSⁱ	CCDS25431.1
RefSeqⁱ	NP_084426.2, NM_030150.2
UniGeneⁱ	Mm.271830

3D structure databases

ProteinModelPortalⁱ	Q99J87
SMRⁱ	Q99J87
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	219822, 1 interactor
STRINGⁱ	10090.ENSMUSP00000017974

PTM databases

iPTMnetⁱ	Q99J87
PhosphoSitePlusⁱ	Q99J87

Proteomic databases

EPDⁱ	Q99J87
MaxQBⁱ	Q99J87
PaxDbⁱ	Q99J87
PRIDEⁱ	Q99J87

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830
GeneIDⁱ	80861
KEGGⁱ	mmu:80861
UCSCⁱ	uc007llx.1 mouse

Organism-specific databases

CTDⁱ	79132
MGIⁱ	MGI:1931560 Dhx58

Phylogenomic databases

eggNOGⁱ	KOG0354 Eukaryota COG1111 LUCA
GeneTreeⁱ	ENSGT00510000046789
HOGENOMⁱ	HOG000230992
HOVERGENⁱ	HBG106019
InParanoidⁱ	Q99J87
KOⁱ	K12649
OMAⁱ	HRAVGNY
OrthoDBⁱ	EOG091G01PQ
TreeFamⁱ	TF330258

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q99J87
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000017830 Expressed in 107 organ(s), highest expression level in bone marrow macrophage
CleanExⁱ	MM_DHX58
Genevisibleⁱ	Q99J87 MM

Family and domain databases

CDDⁱ	cd00079 HELICc, 1 hit
Gene3Dⁱ	2.170.150.30, 1 hit
InterProⁱ	View protein in InterPro IPR006935 Helicase/UvrB_N IPR014001 Helicase_ATP-bd IPR001650 Helicase_C IPR027417 P-loop_NTPase IPR038557 RLR_C_sf IPR021673 RLR_CTR
Pfamⁱ	View protein in Pfam PF00271 Helicase_C, 1 hit PF04851 ResIII, 1 hit PF11648 RIG-I_C-RD, 1 hit
SMARTⁱ	View protein in SMART SM00487 DEXDc, 1 hit SM00490 HELICc, 1 hit
SUPFAMⁱ	SSF52540 SSF52540, 1 hit
PROSITEⁱ	View protein in PROSITE PS51192 HELICASE_ATP_BIND_1, 1 hit PS51194 HELICASE_CTER, 1 hit PS51789 RLR_CTR, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	DHX58_MOUSE
Accessionⁱ	Q99J87Primary (citable) accession number: Q99J87 Secondary accession number(s): A2A5E9, Q9D1X4
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
	Last sequence update:	July 27, 2011
	Last modified:	November 7, 2018
	This is version 134 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q99J87 (DHX58_MOUSE)

Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the ‘basket’ to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>

Probable ATP-dependent RNA helicase DHX58

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Other locations

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

UniProt is an ELIXIR core data resource

Your basket is currently empty. ⁱ

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ