UniProtKB - Q99J87 (DHX58_MOUSE)
Probable ATP-dependent RNA helicase DHX58
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 PublicationsCatalytic activityi
- EC:3.6.4.13
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | 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
- ATP hydrolysis activity Source: RHEA
- DNA binding Source: InterPro
- double-stranded RNA binding Source: MGI
- RNA helicase activity Source: UniProtKB-EC
- single-stranded RNA binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- defense response to virus Source: UniProtKB-KW
- innate immune response Source: GO_Central
- negative regulation of innate immune response Source: UniProtKB
- negative regulation of MDA-5 signaling pathway Source: UniProtKB
- negative regulation of RIG-I signaling pathway Source: UniProtKB
- negative regulation of type I interferon production Source: UniProtKB
- positive regulation of interferon-beta production Source: GO_Central
- positive regulation of MDA-5 signaling pathway Source: UniProtKB
- positive regulation of RIG-I signaling pathway Source: UniProtKB
- positive regulation of type I interferon production Source: UniProtKB
- regulation of innate immune response Source: MGI
- response to bacterium Source: MGI
- response to virus Source: UniProtKB
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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1931560, Dhx58 |
VEuPathDBi | HostDB:ENSMUSG00000017830 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- cytoplasm Source: MGI
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Disruption phenotypei
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 |
MaxQBi | Q99J87 |
PaxDbi | Q99J87 |
PRIDEi | Q99J87 |
ProteomicsDBi | 279533 |
PTM databases
iPTMneti | Q99J87 |
PhosphoSitePlusi | Q99J87 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000017830, Expressed in spermatocyte and 145 other tissues |
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 similarityProtein-protein interaction databases
BioGRIDi | 219822, 2 interactors |
STRINGi | 10090.ENSMUSP00000017974 |
Miscellaneous databases
RNActi | Q99J87, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | 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
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0354, Eukaryota |
GeneTreei | ENSGT00940000153173 |
HOGENOMi | CLU_006888_2_1_1 |
InParanoidi | Q99J87 |
OMAi | HRAVGNY |
OrthoDBi | 1337630at2759 |
PhylomeDBi | Q99J87 |
TreeFami | TF330258 |
Family and domain databases
Gene3Di | 2.170.150.30, 1 hit 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR006935, Helicase/UvrB_N IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR027417, P-loop_NTPase IPR041204, RIG-I_C IPR038557, RLR_C_sf IPR021673, RLR_CTR |
Pfami | View protein in Pfam PF00271, Helicase_C, 1 hit PF04851, ResIII, 1 hit PF18119, RIG-I_C, 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 |
i Sequence
Sequence statusi: Complete.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | 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 No translation available. BC029209 mRNA Translation: AAH29209.1 |
CCDSi | CCDS25431.1 |
RefSeqi | NP_084426.2, NM_030150.2 |
Genome annotation databases
Ensembli | ENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830 |
GeneIDi | 80861 |
KEGGi | mmu:80861 |
UCSCi | uc007llx.1, mouse |
Similar proteinsi
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 No translation available. BC029209 mRNA Translation: AAH29209.1 |
CCDSi | CCDS25431.1 |
RefSeqi | NP_084426.2, NM_030150.2 |
3D structure databases
SMRi | Q99J87 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 219822, 2 interactors |
STRINGi | 10090.ENSMUSP00000017974 |
PTM databases
iPTMneti | Q99J87 |
PhosphoSitePlusi | Q99J87 |
Proteomic databases
EPDi | Q99J87 |
MaxQBi | Q99J87 |
PaxDbi | Q99J87 |
PRIDEi | Q99J87 |
ProteomicsDBi | 279533 |
Protocols and materials databases
Antibodypediai | 16840, 374 antibodies from 36 providers |
DNASUi | 80861 |
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 |
VEuPathDBi | HostDB:ENSMUSG00000017830 |
Phylogenomic databases
eggNOGi | KOG0354, Eukaryota |
GeneTreei | ENSGT00940000153173 |
HOGENOMi | CLU_006888_2_1_1 |
InParanoidi | Q99J87 |
OMAi | HRAVGNY |
OrthoDBi | 1337630at2759 |
PhylomeDBi | Q99J87 |
TreeFami | TF330258 |
Miscellaneous databases
BioGRID-ORCSi | 80861, 3 hits in 65 CRISPR screens |
PROi | PR:Q99J87 |
RNActi | Q99J87, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000017830, Expressed in spermatocyte and 145 other tissues |
Genevisiblei | Q99J87, MM |
Family and domain databases
Gene3Di | 2.170.150.30, 1 hit 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR006935, Helicase/UvrB_N IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR027417, P-loop_NTPase IPR041204, RIG-I_C IPR038557, RLR_C_sf IPR021673, RLR_CTR |
Pfami | View protein in Pfam PF00271, Helicase_C, 1 hit PF04851, ResIII, 1 hit PF18119, RIG-I_C, 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 |
MobiDBi | 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: | February 23, 2022 | |
This is version 151 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
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families