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Protein

Probable ATP-dependent RNA helicase DHX58

Gene

Dhx58

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi556ZincPROSITE-ProRule annotation1
Metal bindingi559ZincPROSITE-ProRule annotation1
Metal bindingi612ZincPROSITE-ProRule annotation1
Metal bindingi615ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi24 – 31ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

  • defense response to virus Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • 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 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 virus Source: UniProtKB

Keywordsi

Molecular functionHelicase, Hydrolase, RNA-binding
Biological processAntiviral defense, Immunity, Innate immunity
LigandATP-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1931560 Dhx58

Subcellular locationi

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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi30K → A: Abolishes IFNB1 production upon infection with various viruses. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001020111 – 678Probable ATP-dependent RNA helicase DHX58Add BLAST678

Proteomic databases

EPDiQ99J87
MaxQBiQ99J87
PaxDbiQ99J87
PRIDEiQ99J87

PTM databases

iPTMnetiQ99J87
PhosphoSitePlusiQ99J87

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

BgeeiENSMUSG00000017830
CleanExiMM_DHX58
GenevisibleiQ99J87 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

BioGridi219822, 1 interactor
STRINGi10090.ENSMUSP00000017974

Structurei

3D structure databases

ProteinModelPortaliQ99J87
SMRiQ99J87
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 188Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST178
Domaini353 – 514Helicase C-terminalPROSITE-ProRule annotationAdd BLAST162
Domaini542 – 669RLR CTRPROSITE-ProRule annotationAdd BLAST128

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni572 – 655RNA-bindingBy similarityAdd BLAST84

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili489 – 546Sequence analysisAdd BLAST58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi131 – 134DECH box4

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

eggNOGiKOG0354 Eukaryota
COG1111 LUCA
GeneTreeiENSGT00510000046789
HOGENOMiHOG000230992
HOVERGENiHBG106019
InParanoidiQ99J87
KOiK12649
OMAiFYEPVPS
OrthoDBiEOG091G01PQ
TreeFamiTF330258

Family and domain databases

CDDicd00079 HELICc, 1 hit
Gene3Di2.170.150.30, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00271 Helicase_C, 1 hit
PF04851 ResIII, 1 hit
PF11648 RIG-I_C-RD, 1 hit
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00490 HELICc, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits
PROSITEiView 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]FASTAAdd 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti638I → M in AAK15474 (PubMed:11161808).Curated1
Sequence conflicti638I → M in AAK15475 (PubMed:11161808).Curated1
Sequence conflicti638I → M in AAH29209 (PubMed:15489334).Curated1

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
CCDSiCCDS25431.1
RefSeqiNP_084426.2, NM_030150.2
UniGeneiMm.271830

Genome annotation databases

EnsembliENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830
GeneIDi80861
KEGGimmu:80861
UCSCiuc007llx.1 mouse

Similar proteinsi

Entry informationi

Entry nameiDHX58_MOUSE
AccessioniPrimary (citable) accession number: Q99J87
Secondary accession number(s): A2A5E9, Q9D1X4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: March 28, 2018
This is version 131 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health