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Protein

Probable ATP-dependent RNA helicase DDX58

Gene

DDX58

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.13 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi810ZincPROSITE-ProRule annotation1
Metal bindingi813ZincPROSITE-ProRule annotation1
Metal bindingi864ZincPROSITE-ProRule annotation1
Metal bindingi869ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi264 – 271ATPCurated8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • double-stranded DNA binding Source: Ensembl
  • double-stranded RNA binding Source: UniProtKB
  • helicase activity Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • single-stranded RNA binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cytoplasmic pattern recognition receptor signaling pathway in response to virus Source: UniProtKB
  • detection of virus Source: BHF-UCL
  • innate immune response Source: UniProtKB
  • negative regulation of type I interferon production Source: Reactome
  • positive regulation of defense response to virus by host Source: UniProtKB
  • positive regulation of gene expression Source: CACAO
  • positive regulation of granulocyte macrophage colony-stimulating factor production Source: CACAO
  • positive regulation of interferon-alpha production Source: UniProtKB
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of interleukin-6 production Source: CACAO
  • positive regulation of interleukin-8 production Source: CACAO
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of transcription factor import into nucleus Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of cell migration Source: UniProtKB
  • regulation of type III interferon production Source: UniProtKB
  • response to exogenous dsRNA Source: Ensembl
  • response to virus Source: UniProtKB
  • RIG-I signaling pathway Source: UniProtKB

Keywordsi

Molecular functionHelicase, Hydrolase, RNA-binding
Biological processAntiviral defense, Host-virus interaction, Immunity, Innate immunity
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
SIGNORiO95786.

Names & Taxonomyi

Protein namesi
Recommended name:
Probable ATP-dependent RNA helicase DDX58 (EC:3.6.4.13)
Alternative name(s):
DEAD box protein 58
RIG-I-like receptor 1
Short name:
RLR-1
Retinoic acid-inducible gene 1 protein
Short name:
RIG-1
Retinoic acid-inducible gene I protein
Short name:
RIG-I
Gene namesi
Name:DDX58
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:19102. DDX58.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: UniProtKB
  • bicellular tight junction Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • ruffle membrane Source: UniProtKB

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

Singleton-Merten syndrome 2 (SGMRT2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Singleton-Merten syndrome, an autosomal dominant disorder characterized by marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extend glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments. SGMRT2 is an atypical form characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies.
See also OMIM:616298
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073667268C → F in SGMRT2; results in constitutive activation and enhanced interferon-mediated signaling. 1 PublicationCorresponds to variant dbSNP:rs786204848Ensembl.1
Natural variantiVAR_073668373E → A in SGMRT2; results in constitutive activation and enhanced interferon-mediated signaling. 1 PublicationCorresponds to variant dbSNP:rs786204847Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi55T → I: No IRF3 signaling activity; no effect on dsRNA binding. 1 Publication1
Mutagenesisi99K → R: Little or no effect on ubiquitination of the 2 CARD domain. Abolishes ubiquitination by RNF125. 2 Publications1
Mutagenesisi154K → R: Reduction of ubiquitination. Reduction of INFB induction. 1 Publication1
Mutagenesisi164K → R: Reduction of ubiquitination. Reduction of INFB induction. 1 Publication1
Mutagenesisi169K → R: Little or no effect on ubiquitination of the 2 CARD domains. 1 Publication1
Mutagenesisi172K → R: Complete loss of ubiquitination; No interaction with MAVS/IPS1; No induction of IFN-beta. 2 Publications1
Mutagenesisi181K → R: Little or no effect on ubiquitination of the 2 CARD domains. 1 Publication1
Mutagenesisi190K → R: Little or no effect on ubiquitination of the 2 CARD domains. 1
Mutagenesisi193K → R: Little or no effect on ubiquitination of the 2 CARD domains. 1 Publication1
Mutagenesisi270K → A: No IRF3 signaling activity. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi23586.
MalaCardsiDDX58.
MIMi616298. phenotype.
OpenTargetsiENSG00000107201.
PharmGKBiPA134994272.

Polymorphism and mutation databases

BioMutaiDDX58.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440931 – 925Probable ATP-dependent RNA helicase DDX58Add BLAST925

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki172Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki181Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei770Phosphothreonine; by CK21 Publication1
Modified residuei854Phosphoserine; by CK21 Publication1
Modified residuei855Phosphoserine; by CK21 Publication1
Modified residuei858N6-acetyllysineCombined sources1

Post-translational modificationi

Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation.1 Publication
ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. ISGylation negatively regulates its function in antiviral signaling response.3 Publications
Sumoylated, probably by MUL1; inhibiting its polyubiquitination.2 Publications
Ubiquitinated. Undergoes 'Lys-48'- and 'Lys-63'-linked ubiquitination. Lys-172 is the critical site for TRIM25-mediated ubiquitination, for MAVS/IPS1 binding and to induce anti-viral signal transduction (PubMed:17392790). Lys-154, Lys-164 and Lys-172 are critical sites for RNF135-mediated and TRIM4-mediated ubiquitination (PubMed:19017631, PubMed:19484123, PubMed:24755855). Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains (PubMed:18636086). Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'-and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor (PubMed:20368735). Ubiquitinated at Lys-181 by RNF125, leading to its degradation: ubiquitination takes place upon viral infection and is enhanced 'Lys-63'-linked ubiquitination of the CARD domains, which promote interaction with VCP/p97 and subsequent recruitment of RNF125 (PubMed:17460044, PubMed:26471729).8 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95786.
MaxQBiO95786.
PaxDbiO95786.
PeptideAtlasiO95786.
PRIDEiO95786.

PTM databases

iPTMnetiO95786.
PhosphoSitePlusiO95786.

Expressioni

Tissue specificityi

Present in vascular smooth cells (at protein level).1 Publication

Inductioni

By bacterial lipopolysaccharides (LPS) in endothelial cells. By interferon (IFN).5 Publications

Gene expression databases

BgeeiENSG00000107201.
CleanExiHS_DDX58.
ExpressionAtlasiO95786. baseline and differential.
GenevisibleiO95786. HS.

Organism-specific databases

HPAiCAB012643.
HPA047193.

Interactioni

Subunit structurei

Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts (via tandem CARD domain) with MAVS/IPS1 promoting its filamentation. Interacts with DHX58/LGP2, IKBKE, TBK1 and TMEM173/STING. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts with RNF135. Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to DDX58. Interacts with SRC. Interacts with DDX60. Interacts with isoform 2 of ZC3HAV1 (via zinc-fingers) in an RNA-dependent manner. Interacts (via tandem CARD domain) with SEC14L1; the interaction is direct and impairs the interaction of DDX58 with MAVS/IPS1. Interacts with VCP/p97; interaction is direct and leads to recruit RNF125 and subsequent ubiquitination and degradation (PubMed:26471729).19 Publications
(Microbial infection) Interacts with protein Z of Guanarito virus, Machupo virus, Junin arenavirus and Sabia virus. This interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction (PubMed:20007272).1 Publication
(Microbial infection) Interacts (via CARD domain) with Human respiratory syncytial virus A non-structural protein 2 (NS2) and this interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 activation (PubMed:19193793).1 Publication
(Microbial infection) Interacts with Rotavirus A non-structural protein 1 (NSP1) and this interaction induces down-regulation of DDX58/RIG-I (PubMed:22152002).1 Publication
(Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction prevents the interaction of MAVS/IPS1 to DDX58 (PubMed:22301138).1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi117121. 41 interactors.
DIPiDIP-35444N.
IntActiO95786. 23 interactors.
MINTiMINT-2799116.
STRINGi9606.ENSP00000369213.

Structurei

Secondary structure

1925
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 11Combined sources10
Helixi13 – 19Combined sources7
Helixi22 – 25Combined sources4
Turni26 – 32Combined sources7
Helixi35 – 48Combined sources14
Helixi50 – 63Combined sources14
Helixi69 – 80Combined sources12
Turni83 – 85Combined sources3
Helixi86 – 91Combined sources6
Helixi95 – 99Combined sources5
Helixi101 – 117Combined sources17
Helixi120 – 127Combined sources8
Helixi128 – 130Combined sources3
Helixi133 – 146Combined sources14
Helixi148 – 160Combined sources13
Helixi167 – 177Combined sources11
Turni183 – 185Combined sources3
Helixi245 – 255Combined sources11
Beta strandi260 – 263Combined sources4
Helixi270 – 284Combined sources15
Beta strandi293 – 296Combined sources4
Helixi300 – 313Combined sources14
Turni314 – 318Combined sources5
Beta strandi321 – 324Combined sources4
Beta strandi326 – 328Combined sources3
Beta strandi330 – 332Combined sources3
Helixi334 – 339Combined sources6
Beta strandi342 – 346Combined sources5
Helixi348 – 356Combined sources9
Beta strandi358 – 360Combined sources3
Helixi363 – 365Combined sources3
Beta strandi367 – 372Combined sources6
Helixi374 – 376Combined sources3
Helixi382 – 395Combined sources14
Beta strandi396 – 398Combined sources3
Beta strandi404 – 410Combined sources7
Helixi420 – 433Combined sources14
Beta strandi438 – 440Combined sources3
Beta strandi443 – 445Combined sources3
Helixi446 – 452Combined sources7
Beta strandi457 – 462Combined sources6
Helixi470 – 489Combined sources20
Helixi493 – 495Combined sources3
Beta strandi496 – 498Combined sources3
Beta strandi504 – 506Combined sources3
Helixi507 – 518Combined sources12
Beta strandi526 – 528Combined sources3
Helixi531 – 557Combined sources27
Helixi560 – 575Combined sources16
Helixi581 – 591Combined sources11
Helixi594 – 602Combined sources9
Helixi604 – 606Combined sources3
Helixi609 – 622Combined sources14
Beta strandi630 – 633Combined sources4
Helixi637 – 649Combined sources13
Helixi651 – 653Combined sources3
Beta strandi658 – 660Combined sources3
Helixi675 – 683Combined sources9
Beta strandi686 – 690Combined sources5
Beta strandi694 – 700Combined sources7
Beta strandi701 – 703Combined sources3
Helixi706 – 708Combined sources3
Beta strandi710 – 716Combined sources7
Helixi721 – 726Combined sources6
Helixi727 – 731Combined sources5
Beta strandi737 – 743Combined sources7
Helixi745 – 768Combined sources24
Helixi773 – 793Combined sources21
Beta strandi801 – 804Combined sources4
Beta strandi806 – 810Combined sources5
Turni811 – 813Combined sources3
Beta strandi816 – 819Combined sources4
Helixi820 – 822Combined sources3
Beta strandi823 – 826Combined sources4
Turni827 – 829Combined sources3
Beta strandi830 – 833Combined sources4
Helixi836 – 839Combined sources4
Beta strandi842 – 846Combined sources5
Beta strandi856 – 864Combined sources9
Turni867 – 869Combined sources3
Beta strandi872 – 879Combined sources8
Beta strandi882 – 887Combined sources6
Helixi889 – 891Combined sources3
Beta strandi892 – 896Combined sources5
Turni897 – 899Combined sources3
Beta strandi902 – 904Combined sources3
Turni908 – 910Combined sources3
Helixi920 – 922Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LWDNMR-A95-190[»]
2LWENMR-A95-190[»]
2QFBX-ray3.00A/B/C/D/E/F/G/H/I/J802-925[»]
2QFDX-ray2.70A/B/C/D/E/F/G/H/I/J802-925[»]
2RMJNMR-A792-925[»]
2YKGX-ray2.50A230-925[»]
3LRNX-ray2.60A/B803-923[»]
3LRRX-ray2.15A/B803-923[»]
3NCUX-ray2.55A/B792-925[»]
3OG8X-ray2.40A/B802-925[»]
3ZD6X-ray2.80A230-925[»]
3ZD7X-ray2.50A230-925[»]
4AY2X-ray2.80A239-925[»]
4BPBX-ray2.58A230-925[»]
4NQKX-ray3.70A/B/C/D1-200[»]
4ON9X-ray2.71A/B230-793[»]
4P4HX-ray3.40A/B/C/D/E/F/G/H1-201[»]
5E3HX-ray2.70A232-925[»]
5F98X-ray3.28A/C/E/G/I/K232-925[»]
5F9FX-ray2.60A/C/E/G/I/K232-925[»]
5F9HX-ray3.10A/C/E/G/I/K232-925[»]
ProteinModelPortaliO95786.
SMRiO95786.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95786.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 87CARD 1Add BLAST87
Domaini92 – 172CARD 2Add BLAST81
Domaini251 – 430Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST180
Domaini610 – 776Helicase C-terminalPROSITE-ProRule annotationAdd BLAST167
Domaini794 – 925RLR CTRPROSITE-ProRule annotationAdd BLAST132

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni218 – 925Interaction with ZC3HAV11 PublicationAdd BLAST708

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi372 – 375DECH box4

Domaini

The RLR CTR domain controls homomultimerization and interaction with MAVS/IPS1. In the absence of viral infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through intramolecular interactions mediated by the RLR CTR domain. Upon binding to viral RNA in the presence of ATP, the RLR CTR domain induces a conformational change exposing the CARD domain and promotes dimerization and CARD interactions with the adapter protein MAVS/IPS1 leading to the induction of downstream signaling.
The helicase domain is responsible for dsRNA recognition.
The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton.
The second CARD domain is the primary site for 'Lys-63'-linked ubiquitination.1 Publication

Sequence similaritiesi

Belongs to the helicase family. RLR subfamily.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0354. Eukaryota.
COG1111. LUCA.
GeneTreeiENSGT00510000046789.
HOGENOMiHOG000230911.
HOVERGENiHBG052325.
InParanoidiO95786.
KOiK12646.
OMAiRTTDRFK.
OrthoDBiEOG091G01PQ.
PhylomeDBiO95786.
TreeFamiTF330258.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProiView protein in InterPro
IPR031964. CARD_dom.
IPR011545. DEAD/DEAH_box_helicase_dom.
IPR011029. DEATH-like_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
PfamiView protein in Pfam
PF16739. CARD_2. 2 hits.
PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SUPFAMiSSF52540. SSF52540. 3 hits.
PROSITEiView protein in PROSITE
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51789. RLR_CTR. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95786-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTTEQRRSLQ AFQDYIRKTL DPTYILSYMA PWFREEEVQY IQAEKNNKGP
60 70 80 90 100
MEAATLFLKF LLELQEEGWF RGFLDALDHA GYSGLYEAIE SWDFKKIEKL
110 120 130 140 150
EEYRLLLKRL QPEFKTRIIP TDIISDLSEC LINQECEEIL QICSTKGMMA
160 170 180 190 200
GAEKLVECLL RSDKENWPKT LKLALEKERN KFSELWIVEK GIKDVETEDL
210 220 230 240 250
EDKMETSDIQ IFYQEDPECQ NLSENSCPPS EVSDTNLYSP FKPRNYQLEL
260 270 280 290 300
ALPAMKGKNT IICAPTGCGK TFVSLLICEH HLKKFPQGQK GKVVFFANQI
310 320 330 340 350
PVYEQQKSVF SKYFERHGYR VTGISGATAE NVPVEQIVEN NDIIILTPQI
360 370 380 390 400
LVNNLKKGTI PSLSIFTLMI FDECHNTSKQ HPYNMIMFNY LDQKLGGSSG
410 420 430 440 450
PLPQVIGLTA SVGVGDAKNT DEALDYICKL CASLDASVIA TVKHNLEELE
460 470 480 490 500
QVVYKPQKFF RKVESRISDK FKYIIAQLMR DTESLAKRIC KDLENLSQIQ
510 520 530 540 550
NREFGTQKYE QWIVTVQKAC MVFQMPDKDE ESRICKALFL YTSHLRKYND
560 570 580 590 600
ALIISEHARM KDALDYLKDF FSNVRAAGFD EIEQDLTQRF EEKLQELESV
610 620 630 640 650
SRDPSNENPK LEDLCFILQE EYHLNPETIT ILFVKTRALV DALKNWIEGN
660 670 680 690 700
PKLSFLKPGI LTGRGKTNQN TGMTLPAQKC ILDAFKASGD HNILIATSVA
710 720 730 740 750
DEGIDIAQCN LVILYEYVGN VIKMIQTRGR GRARGSKCFL LTSNAGVIEK
760 770 780 790 800
EQINMYKEKM MNDSILRLQT WDEAVFREKI LHIQTHEKFI RDSQEKPKPV
810 820 830 840 850
PDKENKKLLC RKCKALACYT ADVRVIEECH YTVLGDAFKE CFVSRPHPKP
860 870 880 890 900
KQFSSFEKRA KIFCARQNCS HDWGIHVKYK TFEIPVIKIE SFVVEDIATG
910 920
VQTLYSKWKD FHFEKIPFDP AEMSK
Length:925
Mass (Da):106,600
Last modified:November 8, 2005 - v2
Checksum:iBF0D501C395BAE25
GO
Isoform 2 (identifier: O95786-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     36-80: Missing.

Note: No experimental confirmation available.
Show »
Length:880
Mass (Da):101,377
Checksum:i4B1603B6F2F37A66
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0237477R → C1 PublicationCorresponds to variant dbSNP:rs10813831Ensembl.1
Natural variantiVAR_073667268C → F in SGMRT2; results in constitutive activation and enhanced interferon-mediated signaling. 1 PublicationCorresponds to variant dbSNP:rs786204848Ensembl.1
Natural variantiVAR_073668373E → A in SGMRT2; results in constitutive activation and enhanced interferon-mediated signaling. 1 PublicationCorresponds to variant dbSNP:rs786204847Ensembl.1
Natural variantiVAR_023748580D → E2 PublicationsCorresponds to variant dbSNP:rs17217280Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01605436 – 80Missing in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038963 mRNA. Translation: AAD19826.1.
AL353671, AL161783 Genomic DNA. Translation: CAH71251.1.
AL161783, AL353671 Genomic DNA. Translation: CAH72600.1.
CH471071 Genomic DNA. Translation: EAW58548.1.
BC132786 mRNA. Translation: AAI32787.1.
BC136610 mRNA. Translation: AAI36611.1.
BX647917 mRNA. Translation: CAI46068.1.
AL137608 mRNA. Translation: CAB70840.1.
CCDSiCCDS6526.1. [O95786-1]
PIRiT46312.
RefSeqiNP_055129.2. NM_014314.3. [O95786-1]
UniGeneiHs.190622.

Genome annotation databases

EnsembliENST00000379883; ENSP00000369213; ENSG00000107201. [O95786-1]
GeneIDi23586.
KEGGihsa:23586.
UCSCiuc003zra.4. human. [O95786-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038963 mRNA. Translation: AAD19826.1.
AL353671, AL161783 Genomic DNA. Translation: CAH71251.1.
AL161783, AL353671 Genomic DNA. Translation: CAH72600.1.
CH471071 Genomic DNA. Translation: EAW58548.1.
BC132786 mRNA. Translation: AAI32787.1.
BC136610 mRNA. Translation: AAI36611.1.
BX647917 mRNA. Translation: CAI46068.1.
AL137608 mRNA. Translation: CAB70840.1.
CCDSiCCDS6526.1. [O95786-1]
PIRiT46312.
RefSeqiNP_055129.2. NM_014314.3. [O95786-1]
UniGeneiHs.190622.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LWDNMR-A95-190[»]
2LWENMR-A95-190[»]
2QFBX-ray3.00A/B/C/D/E/F/G/H/I/J802-925[»]
2QFDX-ray2.70A/B/C/D/E/F/G/H/I/J802-925[»]
2RMJNMR-A792-925[»]
2YKGX-ray2.50A230-925[»]
3LRNX-ray2.60A/B803-923[»]
3LRRX-ray2.15A/B803-923[»]
3NCUX-ray2.55A/B792-925[»]
3OG8X-ray2.40A/B802-925[»]
3ZD6X-ray2.80A230-925[»]
3ZD7X-ray2.50A230-925[»]
4AY2X-ray2.80A239-925[»]
4BPBX-ray2.58A230-925[»]
4NQKX-ray3.70A/B/C/D1-200[»]
4ON9X-ray2.71A/B230-793[»]
4P4HX-ray3.40A/B/C/D/E/F/G/H1-201[»]
5E3HX-ray2.70A232-925[»]
5F98X-ray3.28A/C/E/G/I/K232-925[»]
5F9FX-ray2.60A/C/E/G/I/K232-925[»]
5F9HX-ray3.10A/C/E/G/I/K232-925[»]
ProteinModelPortaliO95786.
SMRiO95786.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117121. 41 interactors.
DIPiDIP-35444N.
IntActiO95786. 23 interactors.
MINTiMINT-2799116.
STRINGi9606.ENSP00000369213.

PTM databases

iPTMnetiO95786.
PhosphoSitePlusiO95786.

Polymorphism and mutation databases

BioMutaiDDX58.

Proteomic databases

EPDiO95786.
MaxQBiO95786.
PaxDbiO95786.
PeptideAtlasiO95786.
PRIDEiO95786.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379883; ENSP00000369213; ENSG00000107201. [O95786-1]
GeneIDi23586.
KEGGihsa:23586.
UCSCiuc003zra.4. human. [O95786-1]

Organism-specific databases

CTDi23586.
DisGeNETi23586.
GeneCardsiDDX58.
HGNCiHGNC:19102. DDX58.
HPAiCAB012643.
HPA047193.
MalaCardsiDDX58.
MIMi609631. gene.
616298. phenotype.
neXtProtiNX_O95786.
OpenTargetsiENSG00000107201.
PharmGKBiPA134994272.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0354. Eukaryota.
COG1111. LUCA.
GeneTreeiENSGT00510000046789.
HOGENOMiHOG000230911.
HOVERGENiHBG052325.
InParanoidiO95786.
KOiK12646.
OMAiRTTDRFK.
OrthoDBiEOG091G01PQ.
PhylomeDBiO95786.
TreeFamiTF330258.

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
SIGNORiO95786.

Miscellaneous databases

ChiTaRSiDDX58. human.
EvolutionaryTraceiO95786.
GeneWikiiRIG-I.
GenomeRNAii23586.
PROiO95786.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107201.
CleanExiHS_DDX58.
ExpressionAtlasiO95786. baseline and differential.
GenevisibleiO95786. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProiView protein in InterPro
IPR031964. CARD_dom.
IPR011545. DEAD/DEAH_box_helicase_dom.
IPR011029. DEATH-like_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
PfamiView protein in Pfam
PF16739. CARD_2. 2 hits.
PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SUPFAMiSSF52540. SSF52540. 3 hits.
PROSITEiView protein in PROSITE
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51789. RLR_CTR. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiDDX58_HUMAN
AccessioniPrimary (citable) accession number: O95786
Secondary accession number(s): A2RU81
, Q5HYE1, Q5VYT1, Q9NT04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: November 8, 2005
Last modified: February 15, 2017
This is version 148 of the entry and version 2 of the sequence. See 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 9
    Human chromosome 9: 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.