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 27-MAR-2024, entry version 168. 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 RIGI. 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 RIGI. 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 RIGI and IFIH1/MDA5 mediated antiviral CC signaling. Cannot initiate antiviral signaling as it lacks the CARD CC domain required for activating MAVS/IPS1-dependent signaling events. CC Can have both negative and positive regulatory functions related to CC RIGI and IFIH1/MDA5 signaling and this role in regulating signaling may CC be complex and could probably depend on characteristics of the CC infecting virus or target cells, or both. Its inhibitory action on RIG- CC I signaling may involve the following mechanisms: competition with RIGI CC for binding to the viral RNA, binding to RIGI and inhibiting its CC dimerization and interaction with MAVS/IPS1, competing with IKBKE in CC its binding to MAVS/IPS1 thereby inhibiting activation of interferon CC regulatory factor 3 (IRF3). Its positive regulatory role may involve CC unwinding or stripping nucleoproteins of viral RNA thereby facilitating CC their recognition by RIGI and IFIH1/MDA5. Involved in the innate immune CC response to various RNA viruses and some DNA viruses such as poxviruses CC and 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 RIGI (via CARD domain), MAVS/IPS1 and DDX60. CC Found in a complex with RIGI and IFIH1/MDA5. Interacts with ANKRD17. CC Directly interacts with ATG5 and ATG12, either as ATG5 and ATG12 CC 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 RIGI 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 SwissPalm; Q96C10; -. DR BioMuta; DHX58; -. DR DMDM; 50401123; -. DR MassIVE; Q96C10; -. DR MaxQB; Q96C10; -. DR PaxDb; 9606-ENSP00000251642; -. DR PeptideAtlas; Q96C10; -. DR ProteomicsDB; 76141; -. DR TopDownProteomics; Q96C10; -. DR Antibodypedia; 16840; 408 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 AGR; HGNC:29517; -. 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; 342391at2759; -. 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; 12 hits in 1148 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 99 other cell types or tissues. DR ExpressionAtlas; Q96C10; baseline and differential. 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:0140374; P:antiviral innate immune response; IBA:GO_Central. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IMP:UniProtKB. 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: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 CDD; cd18075; DEXHc_RLR-3; 1. DR CDD; cd15806; LGP2_C; 1. DR CDD; cd12090; MDA5_ID; 1. DR CDD; cd18802; SF2_C_dicer; 1. DR Gene3D; 1.20.1320.30; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 2.170.150.30; RIG-I-like receptor, C-terminal regulatory domain; 1. 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-like_C. DR InterPro; IPR038557; RLR_C_sf. DR InterPro; IPR021673; RLR_CTR. DR PANTHER; PTHR14074:SF7; ATP-DEPENDENT RNA HELICASE DHX58; 1. DR PANTHER; PTHR14074; HELICASE WITH DEATH DOMAIN-RELATED; 1. 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; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS51789; RLR_CTR; 1. DR Genevisible; Q96C10; HS. 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; uncertain significance; 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 //