DHX58_HUMAN
ID DHX58_HUMAN Reviewed; 678 AA.
AC Q96C10; Q9HAM6;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=ATP-dependent RNA helicase DHX58 {ECO:0000305|PubMed:19211564};
DE EC=3.6.4.13 {ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19403670};
DE AltName: Full=ATP-dependent helicase LGP2 {ECO:0000305|PubMed:19211564};
DE AltName: Full=Protein D11Lgp2 homolog;
DE AltName: Full=RIG-I-like receptor 3;
DE Short=RLR-3;
DE AltName: Full=RIG-I-like receptor LGP2;
DE Short=RLR;
GN Name=DHX58 {ECO:0000312|HGNC:HGNC:29517}; Synonyms=D11LGP2E, LGP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION.
RX PubMed=16116171; DOI=10.4049/jimmunol.175.5.2851;
RA Yoneyama M., Kikuchi M., Matsumoto K., Imaizumi T., Miyagishi M., Taira K.,
RA Foy E., Loo Y.-M., Gale M. Jr., Akira S., Yonehara S., Kato A., Fujita T.;
RT "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and
RT LGP2 in antiviral innate immunity.";
RL J. Immunol. 175:2851-2858(2005).
RN [4]
RP FUNCTION, AND INTERACTION WITH MAVS AND DDX58.
RX PubMed=17020950; DOI=10.1128/jvi.01325-06;
RA Komuro A., Horvath C.M.;
RT "RNA- and virus-independent inhibition of antiviral signaling by RNA
RT helicase LGP2.";
RL J. Virol. 80:12332-12342(2006).
RN [5]
RP FUNCTION, AND INTERACTION WITH DDX58.
RX PubMed=17190814; DOI=10.1073/pnas.0606699104;
RA Saito T., Hirai R., Loo Y.-M., Owen D., Johnson C.L., Sinha S.C., Akira S.,
RA Fujita T., Gale M. Jr.;
RT "Regulation of innate antiviral defenses through a shared repressor domain
RT in RIG-I and LGP2.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:582-587(2007).
RN [6]
RP INTERACTION WITH ATG5 AND ATG12.
RX PubMed=17709747; DOI=10.1073/pnas.0704014104;
RA Jounai N., Takeshita F., Kobiyama K., Sawano A., Miyawaki A., Xin K.Q.,
RA Ishii K.J., Kawai T., Akira S., Suzuki K., Okuda K.;
RT "The Atg5-Atg12 conjugate associates with innate antiviral immune
RT responses.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14050-14055(2007).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=17473309; DOI=10.1126/stke.3842007pe20;
RA Vitour D., Meurs E.F.;
RT "Regulation of interferon production by RIG-I and LGP2: a lesson in self-
RT control.";
RL Sci. STKE 2007:PE20-PE20(2007).
RN [8]
RP FUNCTION, AND SUBUNIT.
RX PubMed=18411269; DOI=10.1074/jbc.m800542200;
RA Murali A., Li X., Ranjith-Kumar C.T., Bhardwaj K., Holzenburg A., Li P.,
RA Kao C.C.;
RT "Structure and function of LGP2, a DEX(D/H) helicase that regulates the
RT innate immunity response.";
RL J. Biol. Chem. 283:15825-15833(2008).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-30; 131-ASP--HIS-134;
RP 167-THR--SER-169; 373-PHE--THR-376; 438-THR--GLU-442 AND 467-GLN--ARG-471.
RX PubMed=19211564; DOI=10.1074/jbc.m807365200;
RA Bamming D., Horvath C.M.;
RT "Regulation of signal transduction by enzymatically inactive antiviral RNA
RT helicase proteins MDA5, RIG-I, and LGP2.";
RL J. Biol. Chem. 284:9700-9712(2009).
RN [10]
RP CATALYTIC ACTIVITY, AND INTERACTION WITH PARAMYXOVIRUSES NON-STRUCTURAL
RP PROTEIN V (MICROBIAL INFECTION).
RX PubMed=19403670; DOI=10.1128/jvi.00153-09;
RA Parisien J.P., Bamming D., Komuro A., Ramachandran A., Rodriguez J.J.,
RA Barber G., Wojahn R.D., Horvath C.M.;
RT "A shared interface mediates paramyxovirus interference with antiviral RNA
RT helicases MDA5 and LGP2.";
RL J. Virol. 83:7252-7260(2009).
RN [11]
RP REVIEW ON FUNCTION.
RX PubMed=21616437; DOI=10.1016/j.immuni.2011.05.003;
RA Loo Y.M., Gale M. Jr.;
RT "Immune signaling by RIG-I-like receptors.";
RL Immunity 34:680-692(2011).
RN [12]
RP FUNCTION.
RX PubMed=21187438; DOI=10.4049/jimmunol.1002862;
RA Broquet A.H., Hirata Y., McAllister C.S., Kagnoff M.F.;
RT "RIG-I/MDA5/MAVS are required to signal a protective IFN response in
RT rotavirus-infected intestinal epithelium.";
RL J. Immunol. 186:1618-1626(2011).
RN [13]
RP FUNCTION.
RX PubMed=21525357; DOI=10.1128/jvi.00302-11;
RA Chopy D., Pothlichet J., Lafage M., Megret F., Fiette L., Si-Tahar M.,
RA Lafon M.;
RT "Ambivalent role of the innate immune response in rabies virus
RT pathogenesis.";
RL J. Virol. 85:6657-6668(2011).
RN [14]
RP INTERACTION WITH DDX60.
RX PubMed=21791617; DOI=10.1128/mcb.01368-10;
RA Miyashita M., Oshiumi H., Matsumoto M., Seya T.;
RT "DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-
RT like receptor-mediated signaling.";
RL Mol. Cell. Biol. 31:3802-3819(2011).
RN [15]
RP REVIEW ON FUNCTION.
RX PubMed=21481967; DOI=10.1016/j.ejcb.2011.01.011;
RA Eisenaecher K., Krug A.;
RT "Regulation of RLR-mediated innate immune signaling--it is all about
RT keeping the balance.";
RL Eur. J. Cell Biol. 91:36-47(2012).
RN [16]
RP REVIEW ON FUNCTION.
RX PubMed=21496944; DOI=10.1016/j.ejcb.2011.01.015;
RA Schmidt A., Rothenfusser S., Hopfner K.P.;
RT "Sensing of viral nucleic acids by RIG-I: from translocation to
RT translation.";
RL Eur. J. Cell Biol. 91:78-85(2012).
RN [17]
RP INTERACTION WITH ANKRD17.
RX PubMed=23711367; DOI=10.1016/j.febslet.2013.05.037;
RA Menning M., Kufer T.A.;
RT "A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and
RT Nod2-mediated inflammatory responses.";
RL FEBS Lett. 587:2137-2142(2013).
RN [18]
RP FUNCTION.
RX PubMed=33440148; DOI=10.1016/j.celrep.2020.108628;
RA Yin X., Riva L., Pu Y., Martin-Sancho L., Kanamune J., Yamamoto Y.,
RA Sakai K., Gotoh S., Miorin L., De Jesus P.D., Yang C.C., Herbert K.M.,
RA Yoh S., Hultquist J.F., Garcia-Sastre A., Chanda S.K.;
RT "MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial
RT Cells.";
RL Cell Rep. 34:108628-108628(2021).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 541-678 IN COMPLEX WITH RNA,
RP FUNCTION, SUBUNIT, MUTAGENESIS OF LYS-634 AND LYS-651, AND ZINC-BINDING
RP SITES.
RX PubMed=19278996; DOI=10.1074/jbc.m900818200;
RA Li X., Ranjith-Kumar C.T., Brooks M.T., Dharmaiah S., Herr A.B., Kao C.,
RA Li P.;
RT "The RIG-I-like receptor LGP2 recognizes the termini of double-stranded
RT RNA.";
RL J. Biol. Chem. 284:13881-13891(2009).
RN [20]
RP STRUCTURE BY NMR OF 546-678, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19380577; DOI=10.1074/jbc.m109.007179;
RA Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R.,
RA Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.;
RT "Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal
RT domains: identification of the RNA recognition loop in RIG-I-like
RT receptors.";
RL J. Biol. Chem. 284:17465-17474(2009).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 537-678, FUNCTION, SUBUNIT,
RP MUTAGENESIS OF LYS-634, AND ZINC-BINDING SITES.
RX PubMed=19208642; DOI=10.1093/nar/gkp059;
RA Pippig D.A., Hellmuth J.C., Cui S., Kirchhofer A., Lammens K., Lammens A.,
RA Schmidt A., Rothenfusser S., Hopfner K.-P.;
RT "The regulatory domain of the RIG-I family ATPase LGP2 senses double-
RT stranded RNA.";
RL Nucleic Acids Res. 37:2014-2025(2009).
RN [22]
RP VARIANT CYS-8, AND TISSUE SPECIFICITY.
RX PubMed=31256877; DOI=10.1016/j.ajhg.2019.06.001;
RG University of Washington Center for Mendelian Genomics, Baylor-Hopkins Center for Mendelian Genomics, Telethon Undiagnosed Diseases Program;
RA Paine I., Posey J.E., Grochowski C.M., Jhangiani S.N., Rosenheck S.,
RA Kleyner R., Marmorale T., Yoon M., Wang K., Robison R., Cappuccio G.,
RA Pinelli M., Magli A., Coban Akdemir Z., Hui J., Yeung W.L., Wong B.K.Y.,
RA Ortega L., Bekheirnia M.R., Bierhals T., Hempel M., Johannsen J.,
RA Santer R., Aktas D., Alikasifoglu M., Bozdogan S., Aydin H., Karaca E.,
RA Bayram Y., Ityel H., Dorschner M., White J.J., Wilichowski E.,
RA Wortmann S.B., Casella E.B., Kitajima J.P., Kok F., Monteiro F.,
RA Muzny D.M., Bamshad M., Gibbs R.A., Sutton V.R., Van Esch H.,
RA Brunetti-Pierri N., Hildebrandt F., Brautbar A., Van den Veyver I.B.,
RA Glass I., Lessel D., Lyon G.J., Lupski J.R.;
RT "Paralog studies augment gene discovery: DDX and DHX genes.";
RL Am. J. Hum. Genet. 105:302-316(2019).
CC -!- FUNCTION: Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated
CC antiviral signaling. Cannot initiate antiviral signaling as it lacks
CC the CARD domain required for activating MAVS/IPS1-dependent signaling
CC events. Can have both negative and positive regulatory functions
CC related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in
CC regulating signaling may be complex and could probably depend on
CC characteristics of the infecting virus or target cells, or both. Its
CC inhibitory action on DDX58/RIG-I signaling may involve the following
CC mechanisms: competition with DDX58/RIG-I for binding to the viral RNA,
CC binding to DDX58/RIG-I and inhibiting its dimerization and interaction
CC with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1
CC thereby inhibiting activation of interferon regulatory factor 3 (IRF3).
CC Its positive regulatory role may involve unwinding or stripping
CC nucleoproteins of viral RNA thereby facilitating their recognition by
CC DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to
CC various RNA viruses and some DNA viruses such as poxviruses and
CC coronavirus SARS-CoV-2, and also to the bacterial pathogen Listeria
CC monocytogenes (PubMed:31256877). Can bind both ssRNA and dsRNA, with a
CC higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated
CC RNA, although it can recognize RNA lacking a 5'-triphosphate.
CC {ECO:0000269|PubMed:16116171, ECO:0000269|PubMed:17020950,
CC ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18411269,
CC ECO:0000269|PubMed:19208642, ECO:0000269|PubMed:19211564,
CC ECO:0000269|PubMed:19278996, ECO:0000269|PubMed:19380577,
CC ECO:0000269|PubMed:21187438, ECO:0000269|PubMed:21525357,
CC ECO:0000269|PubMed:31256877}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19403670};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000305|PubMed:19211564};
CC -!- SUBUNIT: Monomer in the absence of dsRNA. Homodimer in the presence of
CC dsRNA. Interacts with DDX58/RIG-I (via CARD domain), MAVS/IPS1 and
CC DDX60. Found in a complex with DDX58/RIG-I and IFIH1/MDA5. Interacts
CC with ANKRD17. Directly interacts with ATG5 and ATG12, either as ATG5
CC and ATG12 monomers or as ATG12-ATG5 conjugates (PubMed:17709747).
CC {ECO:0000269|PubMed:17020950, ECO:0000269|PubMed:17190814,
CC ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:18411269,
CC ECO:0000269|PubMed:19208642, ECO:0000269|PubMed:19278996,
CC ECO:0000269|PubMed:21791617, ECO:0000269|PubMed:23711367}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via helicase C-terminal
CC domain) with non-structural protein V of paramyxoviruses including
CC human parainfluenza 2 virus, human parainfluenza 5 virus, measles
CC virus, mumps virus, hendra virus and nipah virus.
CC {ECO:0000269|PubMed:19403670}.
CC -!- INTERACTION:
CC Q96C10; Q9UKV8: AGO2; NbExp=2; IntAct=EBI-744193, EBI-528269;
CC Q96C10; Q7L2E3: DHX30; NbExp=2; IntAct=EBI-744193, EBI-1211456;
CC Q96C10; Q9UPY3: DICER1; NbExp=2; IntAct=EBI-744193, EBI-395506;
CC Q96C10; P19525: EIF2AK2; NbExp=2; IntAct=EBI-744193, EBI-640775;
CC Q96C10; P56537: EIF6; NbExp=2; IntAct=EBI-744193, EBI-372243;
CC Q96C10; Q16666: IFI16; NbExp=2; IntAct=EBI-744193, EBI-2867186;
CC Q96C10; O15226: NKRF; NbExp=2; IntAct=EBI-744193, EBI-766011;
CC Q96C10; Q9NUL3: STAU2; NbExp=2; IntAct=EBI-744193, EBI-722938;
CC Q96C10; P11207: P/V; Xeno; NbExp=2; IntAct=EBI-744193, EBI-6148694;
CC Q96C10; P30927: P/V; Xeno; NbExp=2; IntAct=EBI-744193, EBI-6599165;
CC Q96C10; Q9EMA9: P/V; Xeno; NbExp=2; IntAct=EBI-744193, EBI-6598728;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19380577}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, nerve and spleen. Also
CC expressed in the brain. {ECO:0000269|PubMed:31256877}.
CC -!- INDUCTION: By interferon (IFN), virus infection, or intracellular
CC dsRNA.
CC -!- DOMAIN: The RLR CTR domain is capable of inhibiting dimerization and
CC signaling of DDX58/RIG-I and also facilitates binding of dsRNA.
CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK021416; BAB13818.1; -; mRNA.
DR EMBL; BC014949; AAH14949.1; -; mRNA.
DR CCDS; CCDS11416.1; -.
DR RefSeq; NP_077024.2; NM_024119.2.
DR RefSeq; XP_016880548.1; XM_017025059.1.
DR RefSeq; XP_016880549.1; XM_017025060.1.
DR PDB; 2RQA; NMR; -; A=546-678.
DR PDB; 2W4R; X-ray; 2.60 A; A/B/C/D=537-678.
DR PDB; 3EQT; X-ray; 2.00 A; A/B=541-678.
DR PDBsum; 2RQA; -.
DR PDBsum; 2W4R; -.
DR PDBsum; 3EQT; -.
DR AlphaFoldDB; Q96C10; -.
DR SMR; Q96C10; -.
DR BioGRID; 122553; 24.
DR DIP; DIP-60792N; -.
DR IntAct; Q96C10; 21.
DR STRING; 9606.ENSP00000251642; -.
DR iPTMnet; Q96C10; -.
DR PhosphoSitePlus; Q96C10; -.
DR BioMuta; DHX58; -.
DR DMDM; 50401123; -.
DR MassIVE; Q96C10; -.
DR MaxQB; Q96C10; -.
DR PaxDb; Q96C10; -.
DR PeptideAtlas; Q96C10; -.
DR PRIDE; Q96C10; -.
DR ProteomicsDB; 76141; -.
DR TopDownProteomics; Q96C10; -.
DR Antibodypedia; 16840; 377 antibodies from 36 providers.
DR DNASU; 79132; -.
DR Ensembl; ENST00000251642.8; ENSP00000251642.3; ENSG00000108771.13.
DR GeneID; 79132; -.
DR KEGG; hsa:79132; -.
DR MANE-Select; ENST00000251642.8; ENSP00000251642.3; NM_024119.3; NP_077024.2.
DR UCSC; uc002hyw.5; human.
DR CTD; 79132; -.
DR DisGeNET; 79132; -.
DR GeneCards; DHX58; -.
DR HGNC; HGNC:29517; DHX58.
DR HPA; ENSG00000108771; Low tissue specificity.
DR MIM; 608588; gene.
DR neXtProt; NX_Q96C10; -.
DR OpenTargets; ENSG00000108771; -.
DR PharmGKB; PA162383566; -.
DR VEuPathDB; HostDB:ENSG00000108771; -.
DR eggNOG; KOG0354; Eukaryota.
DR GeneTree; ENSGT00940000153173; -.
DR HOGENOM; CLU_006888_2_1_1; -.
DR InParanoid; Q96C10; -.
DR OMA; HRAVGNY; -.
DR OrthoDB; 1337630at2759; -.
DR PhylomeDB; Q96C10; -.
DR TreeFam; TF330258; -.
DR PathwayCommons; Q96C10; -.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR SignaLink; Q96C10; -.
DR BioGRID-ORCS; 79132; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; DHX58; human.
DR EvolutionaryTrace; Q96C10; -.
DR GeneWiki; LGP2; -.
DR GenomeRNAi; 79132; -.
DR Pharos; Q96C10; Tbio.
DR PRO; PR:Q96C10; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q96C10; protein.
DR Bgee; ENSG00000108771; Expressed in granulocyte and 97 other tissues.
DR ExpressionAtlas; Q96C10; baseline and differential.
DR Genevisible; Q96C10; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0003724; F:RNA helicase activity; IMP:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0039528; P:cytoplasmic pattern recognition receptor signaling pathway in response to virus; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0045824; P:negative regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0039534; P:negative regulation of MDA-5 signaling pathway; IMP:UniProtKB.
DR GO; GO:0039536; P:negative regulation of RIG-I signaling pathway; IDA:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IDA:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IBA:GO_Central.
DR GO; GO:1900245; P:positive regulation of MDA-5 signaling pathway; ISS:UniProtKB.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; ISS:UniProtKB.
DR Gene3D; 2.170.150.30; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR006935; Helicase/UvrB_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041204; RIG-I_C.
DR InterPro; IPR038557; RLR_C_sf.
DR InterPro; IPR021673; RLR_CTR.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF04851; ResIII; 1.
DR Pfam; PF18119; RIG-I_C; 1.
DR Pfam; PF11648; RIG-I_C-RD; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51789; RLR_CTR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; ATP-binding; Coiled coil; Cytoplasm;
KW Helicase; Host-virus interaction; Hydrolase; Immunity; Innate immunity;
KW Metal-binding; Nucleotide-binding; Reference proteome; RNA-binding; Zinc.
FT CHAIN 1..678
FT /note="ATP-dependent RNA helicase DHX58"
FT /id="PRO_0000102010"
FT DOMAIN 11..188
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 350..514
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 539..669
FT /note="RLR CTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT REGION 572..655
FT /note="RNA-binding"
FT COILED 489..546
FT /evidence="ECO:0000255"
FT MOTIF 131..134
FT /note="DECH box"
FT BINDING 24..31
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 556
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 559
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 612
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 615
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT VARIANT 8
FT /note="W -> C (found in a patient with a neurodevelopmental
FT disorder; unknown pathological significance;
FT dbSNP:rs200502586)"
FT /evidence="ECO:0000269|PubMed:31256877"
FT /id="VAR_083645"
FT VARIANT 76
FT /note="T -> A (in dbSNP:rs34891485)"
FT /id="VAR_049336"
FT VARIANT 95
FT /note="R -> Q (in dbSNP:rs35118457)"
FT /id="VAR_049337"
FT VARIANT 425
FT /note="Q -> R (in dbSNP:rs2074158)"
FT /id="VAR_019394"
FT VARIANT 523
FT /note="R -> Q (in dbSNP:rs2074160)"
FT /id="VAR_019395"
FT MUTAGEN 30
FT /note="K->A: Loss of dsRNA-induced ATPase activity. No
FT effect on ds-RNA binding. No effect on cytoplasmic pattern
FT recognition receptor signaling pathway in response to
FT virus."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 131..134
FT /note="DECH->AACA: Loss of dsRNA-induced ATPase activity."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 167..169
FT /note="TAS->AAA: Loss of dsRNA-induced ATPase activity.
FT Loss of ds-RNA binding. No effect on cytoplasmic pattern
FT recognition receptor signaling pathway in response to
FT virus."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 373..376
FT /note="FTRT->ATRA: Loss of dsRNA-induced ATPase activity.
FT No effect on cytoplasmic pattern recognition receptor
FT signaling pathway in response to virus."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 438..442
FT /note="TSVAE->ASVAA: Loss of dsRNA-induced ATPase activity.
FT No effect on cytoplasmic pattern recognition receptor
FT signaling pathway in response to virus."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 467..471
FT /note="QARGR->AARGA: Loss of dsRNA-induced ATPase activity.
FT No effect on cytoplasmic pattern recognition receptor
FT signaling pathway in response to virus."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 634
FT /note="K->E: Abolishes RNA binding."
FT /evidence="ECO:0000269|PubMed:19208642,
FT ECO:0000269|PubMed:19278996"
FT MUTAGEN 651
FT /note="K->E: Abolishes RNA binding."
FT /evidence="ECO:0000269|PubMed:19278996"
FT CONFLICT 473
FT /note="R -> W (in Ref. 1; BAB13818)"
FT /evidence="ECO:0000305"
FT HELIX 549..551
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 553..556
FT /evidence="ECO:0007829|PDB:3EQT"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 562..565
FT /evidence="ECO:0007829|PDB:3EQT"
FT HELIX 566..568
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 569..572
FT /evidence="ECO:0007829|PDB:3EQT"
FT TURN 573..575
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 576..579
FT /evidence="ECO:0007829|PDB:3EQT"
FT HELIX 582..587
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 588..590
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 592..594
FT /evidence="ECO:0007829|PDB:2RQA"
FT STRAND 597..599
FT /evidence="ECO:0007829|PDB:2RQA"
FT STRAND 602..612
FT /evidence="ECO:0007829|PDB:3EQT"
FT TURN 613..615
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 618..625
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 628..633
FT /evidence="ECO:0007829|PDB:3EQT"
FT HELIX 635..637
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 638..642
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:3EQT"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:3EQT"
FT STRAND 655..657
FT /evidence="ECO:0007829|PDB:2W4R"
FT HELIX 664..671
FT /evidence="ECO:0007829|PDB:3EQT"
FT HELIX 675..677
FT /evidence="ECO:0007829|PDB:3EQT"
SQ SEQUENCE 678 AA; 76613 MW; 859E1749C7313D06 CRC64;
MELRSYQWEV IMPALEGKNI IIWLPTGAGK TRAAAYVAKR HLETVDGAKV VVLVNRVHLV
TQHGEEFRRM LDGRWTVTTL SGDMGPRAGF GHLARCHDLL ICTAELLQMA LTSPEEEEHV
ELTVFSLIVV DECHHTHKDT VYNVIMSQYL ELKLQRAQPL PQVLGLTASP GTGGASKLDG
AINHVLQLCA NLDTWCIMSP QNCCPQLQEH SQQPCKQYNL CHRRSQDPFG DLLKKLMDQI
HDHLEMPELS RKFGTQMYEQ QVVKLSEAAA LAGLQEQRVY ALHLRRYNDA LLIHDTVRAV
DALAALQDFY HREHVTKTQI LCAERRLLAL FDDRKNELAH LATHGPENPK LEMLEKILQR
QFSSSNSPRG IIFTRTRQSA HSLLLWLQQQ QGLQTVDIRA QLLIGAGNSS QSTHMTQRDQ
QEVIQKFQDG TLNLLVATSV AEEGLDIPHC NVVVRYGLLT NEISMVQARG RARADQSVYA
FVATEGSREL KRELINEALE TLMEQAVAAV QKMDQAEYQA KIRDLQQAAL TKRAAQAAQR
ENQRQQFPVE HVQLLCINCM VAVGHGSDLR KVEGTHHVNV NPNFSNYYNV SRDPVVINKV
FKDWKPGGVI SCRNCGEVWG LQMIYKSVKL PVLKVRSMLL ETPQGRIQAK KWSRVPFSVP
DFDFLQHCAE NLSDLSLD
