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Protein

Probable ATP-dependent RNA helicase DHX58

Gene

DHX58

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.10 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

  • ATP binding Source: UniProtKB-KW
  • DNA binding Source: InterPro
  • double-stranded RNA binding Source: UniProtKB
  • helicase activity Source: UniProtKB-KW
  • single-stranded RNA binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108771-MONOMER.
ReactomeiR-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

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 homolog
RIG-I-like receptor 3
Short name:
RLR-3
RIG-I-like receptor LGP2
Short name:
RLR
Gene namesi
Name:DHX58
Synonyms:D11LGP2E, LGP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:29517. DHX58.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi634K → E: Abolishes RNA binding. 2 Publications1
Mutagenesisi651K → E: Abolishes RNA binding. 1 Publication1

Organism-specific databases

DisGeNETi79132.
OpenTargetsiENSG00000108771.
PharmGKBiPA162383566.

Polymorphism and mutation databases

BioMutaiDHX58.
DMDMi50401123.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001020101 – 678Probable ATP-dependent RNA helicase DHX58Add BLAST678

Proteomic databases

MaxQBiQ96C10.
PaxDbiQ96C10.
PeptideAtlasiQ96C10.
PRIDEiQ96C10.
TopDownProteomicsiQ96C10.

PTM databases

iPTMnetiQ96C10.
PhosphoSitePlusiQ96C10.

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000108771.
CleanExiHS_DHX58.
ExpressionAtlasiQ96C10. baseline and differential.
GenevisibleiQ96C10. HS.

Organism-specific databases

HPAiHPA018670.
HPA019570.

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 (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. Interacts with ANKRD17.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGO2Q9UKV82EBI-744193,EBI-528269
DHX30Q7L2E32EBI-744193,EBI-1211456
DICER1Q9UPY32EBI-744193,EBI-395506
EIF2AK2P195252EBI-744193,EBI-640775
EIF6P565372EBI-744193,EBI-372243
NKRFO152262EBI-744193,EBI-766011
P/VP112072EBI-744193,EBI-6148694From a different organism.
P/VP309272EBI-744193,EBI-6599165From a different organism.
P/VQ9EMA92EBI-744193,EBI-6598728From a different organism.
STAU2Q9NUL32EBI-744193,EBI-722938

Protein-protein interaction databases

BioGridi122553. 13 interactors.
DIPiDIP-60792N.
IntActiQ96C10. 18 interactors.
MINTiMINT-1460040.
STRINGi9606.ENSP00000251642.

Structurei

Secondary structure

1678
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi549 – 551Combined sources3
Beta strandi553 – 556Combined sources4
Turni557 – 559Combined sources3
Beta strandi562 – 565Combined sources4
Helixi566 – 568Combined sources3
Beta strandi569 – 572Combined sources4
Turni573 – 575Combined sources3
Beta strandi576 – 579Combined sources4
Helixi582 – 587Combined sources6
Beta strandi588 – 590Combined sources3
Beta strandi592 – 594Combined sources3
Beta strandi597 – 599Combined sources3
Beta strandi602 – 612Combined sources11
Turni613 – 615Combined sources3
Beta strandi618 – 625Combined sources8
Beta strandi628 – 633Combined sources6
Helixi635 – 637Combined sources3
Beta strandi638 – 642Combined sources5
Beta strandi645 – 647Combined sources3
Helixi652 – 654Combined sources3
Beta strandi655 – 657Combined sources3
Helixi664 – 671Combined sources8
Helixi675 – 677Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RQANMR-A546-678[»]
2W4RX-ray2.60A/B/C/D537-678[»]
3EQTX-ray2.00A/B541-678[»]
ProteinModelPortaliQ96C10.
SMRiQ96C10.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96C10.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 188Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST178
Domaini350 – 514Helicase C-terminalPROSITE-ProRule annotationAdd BLAST165
Domaini539 – 669RLR CTRPROSITE-ProRule annotationAdd BLAST131

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni572 – 655RNA-bindingAdd 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
Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation
Contains 1 RLR CTR (RLR C-terminal regulatory) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0354. Eukaryota.
COG1111. LUCA.
GeneTreeiENSGT00510000046789.
HOGENOMiHOG000230992.
HOVERGENiHBG106019.
InParanoidiQ96C10.
KOiK12649.
OMAiSPRGIIF.
OrthoDBiEOG091G01PQ.
PhylomeDBiQ96C10.
TreeFamiTF330258.

Family and domain databases

Gene3Di3.30.450.40. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR029016. GAF_dom-like.
IPR006935. Helicase/UvrB_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamiPF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51789. RLR_CTR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q96C10-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELRSYQWEV IMPALEGKNI IIWLPTGAGK TRAAAYVAKR HLETVDGAKV
60 70 80 90 100
VVLVNRVHLV TQHGEEFRRM LDGRWTVTTL SGDMGPRAGF GHLARCHDLL
110 120 130 140 150
ICTAELLQMA LTSPEEEEHV ELTVFSLIVV DECHHTHKDT VYNVIMSQYL
160 170 180 190 200
ELKLQRAQPL PQVLGLTASP GTGGASKLDG AINHVLQLCA NLDTWCIMSP
210 220 230 240 250
QNCCPQLQEH SQQPCKQYNL CHRRSQDPFG DLLKKLMDQI HDHLEMPELS
260 270 280 290 300
RKFGTQMYEQ QVVKLSEAAA LAGLQEQRVY ALHLRRYNDA LLIHDTVRAV
310 320 330 340 350
DALAALQDFY HREHVTKTQI LCAERRLLAL FDDRKNELAH LATHGPENPK
360 370 380 390 400
LEMLEKILQR QFSSSNSPRG IIFTRTRQSA HSLLLWLQQQ QGLQTVDIRA
410 420 430 440 450
QLLIGAGNSS QSTHMTQRDQ QEVIQKFQDG TLNLLVATSV AEEGLDIPHC
460 470 480 490 500
NVVVRYGLLT NEISMVQARG RARADQSVYA FVATEGSREL KRELINEALE
510 520 530 540 550
TLMEQAVAAV QKMDQAEYQA KIRDLQQAAL TKRAAQAAQR ENQRQQFPVE
560 570 580 590 600
HVQLLCINCM VAVGHGSDLR KVEGTHHVNV NPNFSNYYNV SRDPVVINKV
610 620 630 640 650
FKDWKPGGVI SCRNCGEVWG LQMIYKSVKL PVLKVRSMLL ETPQGRIQAK
660 670
KWSRVPFSVP DFDFLQHCAE NLSDLSLD
Length:678
Mass (Da):76,613
Last modified:December 1, 2001 - v1
Checksum:i859E1749C7313D06
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti473R → W in BAB13818 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04933676T → A.Corresponds to variant rs34891485dbSNPEnsembl.1
Natural variantiVAR_04933795R → Q.Corresponds to variant rs35118457dbSNPEnsembl.1
Natural variantiVAR_019394425Q → R.Corresponds to variant rs2074158dbSNPEnsembl.1
Natural variantiVAR_019395523R → Q.Corresponds to variant rs2074160dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK021416 mRNA. Translation: BAB13818.1.
BC014949 mRNA. Translation: AAH14949.1.
CCDSiCCDS11416.1.
RefSeqiNP_077024.2. NM_024119.2.
XP_016880548.1. XM_017025059.1.
XP_016880549.1. XM_017025060.1.
UniGeneiHs.55918.

Genome annotation databases

EnsembliENST00000251642; ENSP00000251642; ENSG00000108771.
GeneIDi79132.
KEGGihsa:79132.
UCSCiuc002hyw.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK021416 mRNA. Translation: BAB13818.1.
BC014949 mRNA. Translation: AAH14949.1.
CCDSiCCDS11416.1.
RefSeqiNP_077024.2. NM_024119.2.
XP_016880548.1. XM_017025059.1.
XP_016880549.1. XM_017025060.1.
UniGeneiHs.55918.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RQANMR-A546-678[»]
2W4RX-ray2.60A/B/C/D537-678[»]
3EQTX-ray2.00A/B541-678[»]
ProteinModelPortaliQ96C10.
SMRiQ96C10.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122553. 13 interactors.
DIPiDIP-60792N.
IntActiQ96C10. 18 interactors.
MINTiMINT-1460040.
STRINGi9606.ENSP00000251642.

PTM databases

iPTMnetiQ96C10.
PhosphoSitePlusiQ96C10.

Polymorphism and mutation databases

BioMutaiDHX58.
DMDMi50401123.

Proteomic databases

MaxQBiQ96C10.
PaxDbiQ96C10.
PeptideAtlasiQ96C10.
PRIDEiQ96C10.
TopDownProteomicsiQ96C10.

Protocols and materials databases

DNASUi79132.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000251642; ENSP00000251642; ENSG00000108771.
GeneIDi79132.
KEGGihsa:79132.
UCSCiuc002hyw.5. human.

Organism-specific databases

CTDi79132.
DisGeNETi79132.
GeneCardsiDHX58.
HGNCiHGNC:29517. DHX58.
HPAiHPA018670.
HPA019570.
MIMi608588. gene.
neXtProtiNX_Q96C10.
OpenTargetsiENSG00000108771.
PharmGKBiPA162383566.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0354. Eukaryota.
COG1111. LUCA.
GeneTreeiENSGT00510000046789.
HOGENOMiHOG000230992.
HOVERGENiHBG106019.
InParanoidiQ96C10.
KOiK12649.
OMAiSPRGIIF.
OrthoDBiEOG091G01PQ.
PhylomeDBiQ96C10.
TreeFamiTF330258.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108771-MONOMER.
ReactomeiR-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

Miscellaneous databases

ChiTaRSiDHX58. human.
EvolutionaryTraceiQ96C10.
GeneWikiiLGP2.
GenomeRNAii79132.
PROiQ96C10.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108771.
CleanExiHS_DHX58.
ExpressionAtlasiQ96C10. baseline and differential.
GenevisibleiQ96C10. HS.

Family and domain databases

Gene3Di3.30.450.40. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR029016. GAF_dom-like.
IPR006935. Helicase/UvrB_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamiPF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51789. RLR_CTR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDHX58_HUMAN
AccessioniPrimary (citable) accession number: Q96C10
Secondary accession number(s): Q9HAM6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.