ID IFIH1_HUMAN Reviewed; 1025 AA. AC Q9BYX4; Q2NKL6; Q6DC96; Q86X56; Q96MX8; Q9H3G6; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 3. DT 27-MAR-2024, entry version 198. DE RecName: Full=Interferon-induced helicase C domain-containing protein 1 {ECO:0000305}; DE EC=3.6.4.13 {ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:22160685}; DE AltName: Full=Clinically amyopathic dermatomyositis autoantigen 140 kDa; DE Short=CADM-140 autoantigen; DE AltName: Full=Helicase with 2 CARD domains; DE Short=Helicard; DE AltName: Full=Interferon-induced with helicase C domain protein 1; DE AltName: Full=Melanoma differentiation-associated protein 5; DE Short=MDA-5; DE AltName: Full=Murabutide down-regulated protein; DE AltName: Full=RIG-I-like receptor 2; DE Short=RLR-2; DE AltName: Full=RNA helicase-DEAD box protein 116; GN Name=IFIH1 {ECO:0000312|HGNC:HGNC:18873}; GN Synonyms=MDA5 {ECO:0000303|PubMed:19211564, GN ECO:0000303|PubMed:33727702}, RH116; 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 [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RC TISSUE=Melanoma; RX PubMed=11805321; DOI=10.1073/pnas.022637199; RA Kang D.-C., Gopalkrishnan R.V., Wu Q., Jankowsky E., Pyle A.M., RA Fisher P.B.; RT "mda-5: an interferon-inducible putative RNA helicase with double-stranded RT RNA-dependent ATPase activity and melanoma growth-suppressive properties."; RL Proc. Natl. Acad. Sci. U.S.A. 99:637-642(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND VARIANT ARG-843. RC TISSUE=Spleen; RX PubMed=14645903; DOI=10.1099/vir.0.19300-0; RA Cocude C., Truong M.-J., Billaut-Mulot O., Delsart V., Darcissac E., RA Capron A., Mouton Y., Bahr G.M.; RT "A novel cellular RNA helicase, RH116, differentially regulates cell RT growth, programmed cell death and human immunodeficiency virus type 1 RT replication."; RL J. Gen. Virol. 84:3215-3225(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP ARG-843 AND THR-946. RC TISSUE=Uterus; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 475-1025 (ISOFORM 1), AND VARIANTS ARG-843 RP AND THR-946. 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 [5] RP MUTAGENESIS OF ASP-251 AND GLU-444, AND TISSUE SPECIFICITY. RX PubMed=12015121; DOI=10.1016/s0960-9822(02)00842-4; RA Kovacsovics M., Martinon F., Micheau O., Bodmer J.-L., Hofmann K., RA Tschopp J.; RT "Overexpression of Helicard, a CARD-containing helicase cleaved during RT apoptosis, accelerates DNA degradation."; RL Curr. Biol. 12:838-843(2002). RN [6] RP ERRATUM OF PUBMED:12015121. RA Kovacsovics M., Martinon F., Micheau O., Bodmer J.-L., Hofmann K., RA Tschopp J.; RL Curr. Biol. 12:1633-1633(2002). RN [7] RP INTERACTION WITH PARAMYXOVIRUSES V PROTEIN (MICROBIAL INFECTION). RX PubMed=15563593; DOI=10.1073/pnas.0407639101; RA Andrejeva J., Childs K.S., Young D.F., Carlos T.S., Stock N., Goodbourn S., RA Randall R.E.; RT "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, RT mda-5, and inhibit its activation of the IFN-beta promoter."; RL Proc. Natl. Acad. Sci. U.S.A. 101:17264-17269(2004). RN [8] RP INTERACTION WITH MAVS/IPS1. RX PubMed=16127453; DOI=10.1038/ni1243; RA Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., RA Takeuchi O., Akira S.; RT "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon RT induction."; RL Nat. Immunol. 6:981-988(2005). RN [9] RP INTERACTION WITH MAVS/IPS1. RX PubMed=16177806; DOI=10.1038/nature04193; RA Meylan E., Curran J., Hofmann K., Moradpour D., Binder M., RA Bartenschlager R., Tschopp J.; RT "Cardif is an adaptor protein in the RIG-I antiviral pathway and is RT targeted by hepatitis C virus."; RL Nature 437:1167-1172(2005). RN [10] RP UBIQUITINATION. RX PubMed=17460044; DOI=10.1073/pnas.0611551104; RA Arimoto K., Takahashi H., Hishiki T., Konishi H., Fujita T., Shimotohno K.; RT "Negative regulation of the RIG-I signaling by the ubiquitin ligase RT RNF125."; RL Proc. Natl. Acad. Sci. U.S.A. 104:7500-7505(2007). RN [11] RP INTERACTION WITH IKBKE; MAVS AND TKFC. RX PubMed=17600090; DOI=10.1073/pnas.0700544104; RA Diao F., Li S., Tian Y., Zhang M., Xu L.G., Zhang Y., Wang R.P., Chen D., RA Zhai Z., Zhong B., Tien P., Shu H.B.; RT "Negative regulation of MDA5- but not RIG-I-mediated innate antiviral RT signaling by the dihydroxyacetone kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 104:11706-11711(2007). RN [12] 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 [13] RP INVOLVEMENT IN CLINICALLY AMYOPATHIC DERMATOMYOSITIS, AND IDENTIFICATION AS RP CADM-140 AUTOANTIGEN. RX PubMed=19565506; DOI=10.1002/art.24621; RA Sato S., Hoshino K., Satoh T., Fujita T., Kawakami Y., Fujita T., RA Kuwana M.; RT "RNA helicase encoded by melanoma differentiation-associated gene 5 is a RT major autoantigen in patients with clinically amyopathic dermatomyositis: RT Association with rapidly progressive interstitial lung disease."; RL Arthritis Rheum. 60:2193-2200(2009). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-335; 443-ASP--HIS-446; RP 488-THR--SER-490; 789-THR--GLU-793 AND 818-GLN--ARG-822. 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 [15] RP FUNCTION. RX PubMed=19656871; DOI=10.1128/jvi.00770-09; RA Pichlmair A., Schulz O., Tan C.P., Rehwinkel J., Kato H., Takeuchi O., RA Akira S., Way M., Schiavo G., Reis e Sousa C.; RT "Activation of MDA5 requires higher-order RNA structures generated during RT virus infection."; RL J. Virol. 83:10761-10769(2009). RN [16] RP INTERACTION WITH PCBP2. RX PubMed=19881509; DOI=10.1038/ni.1815; RA You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.; RT "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin RT ligase AIP4."; RL Nat. Immunol. 10:1300-1308(2009). RN [17] RP INTERACTION WITH NLRC5. RX PubMed=20434986; DOI=10.1016/j.cell.2010.03.040; RA Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., RA Zheng S., Chen Z.J., Wang R.F.; RT "NLRC5 negatively regulates the NF-kappaB and type I interferon signaling RT pathways."; RL Cell 141:483-496(2010). RN [18] RP UBIQUITINATION, AND DEUBIQUITINATION BY USP17L2. RX PubMed=20368735; DOI=10.1038/cr.2010.41; RA Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B.; RT "The ubiquitin-specific protease 17 is involved in virus-triggered type I RT IFN signaling."; RL Cell Res. 20:802-811(2010). RN [19] RP INTERACTION WITH DDX3X. RX PubMed=20127681; DOI=10.1002/eji.200940203; RA Oshiumi H., Sakai K., Matsumoto M., Seya T.; RT "DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate RT IFN-beta-inducing potential."; RL Eur. J. Immunol. 40:940-948(2010). RN [20] RP INVOLVEMENT IN CLINICALLY AMYOPATHIC DERMATOMYOSITIS, IDENTIFICATION AS RP CADM-140 AUTOANTIGEN, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=20015976; DOI=10.1093/rheumatology/kep375; RA Nakashima R., Imura Y., Kobayashi S., Yukawa N., Yoshifuji H., Nojima T., RA Kawabata D., Ohmura K., Usui T., Fujii T., Okawa K., Mimori T.; RT "The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific RT autoantigen identified by the anti-CADM-140 antibody."; RL Rheumatology 49:433-440(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [23] 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 [24] RP REVIEW ON FUNCTION. RX PubMed=21884169; DOI=10.1111/j.1600-065x.2011.01052.x; RA Kato H., Takahasi K., Fujita T.; RT "RIG-I-like receptors: cytoplasmic sensors for non-self RNA."; RL Immunol. Rev. 243:91-98(2011). RN [25] RP FUNCTION. RX PubMed=21742966; DOI=10.4049/jimmunol.1100361; RA Jiang M., Osterlund P., Sarin L.P., Poranen M.M., Bamford D.H., Guo D., RA Julkunen I.; RT "Innate immune responses in human monocyte-derived dendritic cells are RT highly dependent on the size and the 5' phosphorylation of RNA molecules."; RL J. Immunol. 187:1713-1721(2011). RN [26] RP REVIEW ON FUNCTION. RX PubMed=20950133; DOI=10.1089/jir.2010.0057; RA Onoguchi K., Yoneyama M., Fujita T.; RT "Retinoic acid-inducible gene-I-like receptors."; RL J. Interferon Cytokine Res. 31:27-31(2011). RN [27] 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 [28] RP SUMOYLATION, AND INTERACTION WITH PIAS2-BETA. RX PubMed=21156324; DOI=10.1016/j.molimm.2010.09.003; RA Fu J., Xiong Y., Xu Y., Cheng G., Tang H.; RT "MDA5 is SUMOylated by PIAS2? in the upregulation of type I interferon RT signaling."; RL Mol. Immunol. 48:415-422(2011). RN [29] RP REVIEW ON FUNCTION. RX PubMed=21245900; DOI=10.1038/ni0211-114; RA Garcia-Sastre A.; RT "2 methylate or not 2 methylate: viral evasion of the type I interferon RT response."; RL Nat. Immunol. 12:114-115(2011). RN [30] RP FUNCTION. RX PubMed=21217758; DOI=10.1038/ni.1979; RA Zuest R., Cervantes-Barragan L., Habjan M., Maier R., Neuman B.W., RA Ziebuhr J., Szretter K.J., Baker S.C., Barchet W., Diamond M.S., RA Siddell S.G., Ludewig B., Thiel V.; RT "Ribose 2'-O-methylation provides a molecular signature for the distinction RT of self and non-self mRNA dependent on the RNA sensor Mda5."; RL Nat. Immunol. 12:137-143(2011). RN [31] RP SUBUNIT, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22160685; DOI=10.1073/pnas.1113651108; RA Peisley A., Lin C., Wu B., Orme-Johnson M., Liu M., Walz T., Hur S.; RT "Cooperative assembly and dynamic disassembly of MDA5 filaments for viral RT dsRNA recognition."; RL Proc. Natl. Acad. Sci. U.S.A. 108:21010-21015(2011). RN [32] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN US11 (MICROBIAL INFECTION). RX PubMed=22301138; DOI=10.1128/jvi.06713-11; RA Xing J., Wang S., Lin R., Mossman K.L., Zheng C.; RT "Herpes simplex virus 1 tegument protein US11 downmodulates the RLR RT signaling pathway via direct interaction with RIG-I and MDA-5."; RL J. Virol. 86:3528-3540(2012). RN [33] 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 [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [35] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION). RX PubMed=24390337; DOI=10.1128/jvi.02712-13; RA Feng Q., Langereis M.A., Lork M., Nguyen M., Hato S.V., Lanke K., Emdad L., RA Bhoopathi P., Fisher P.B., Lloyd R.E., van Kuppeveld F.J.; RT "Enterovirus 2Apro targets MDA5 and MAVS in infected cells."; RL J. Virol. 88:3369-3378(2014). RN [36] RP PHOSPHORYLATION AT SER-828, AND MUTAGENESIS OF SER-828 AND THR-829. RX PubMed=25865883; DOI=10.1016/j.celrep.2015.03.027; RA Takashima K., Oshiumi H., Takaki H., Matsumoto M., Seya T.; RT "RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and RT attenuates the innate immune response."; RL Cell Rep. 11:192-200(2015). RN [37] RP INTERACTION WITH ECSIT. RX PubMed=25228397; DOI=10.1159/000365971; RA Lei C.Q., Zhang Y., Li M., Jiang L.Q., Zhong B., Kim Y.H., Shu H.B.; RT "ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate RT antiviral responses."; RL J. Innate Immun. 7:153-164(2015). RN [38] RP INTERACTION WITH RNF123. RX PubMed=27312109; DOI=10.15252/embr.201541703; RA Wang S., Yang Y.K., Chen T., Zhang H., Yang W.W., Song S.S., Zhai Z.H., RA Chen D.Y.; RT "RNF123 has an E3 ligase-independent function in RIG-I-like receptor- RT mediated antiviral signaling."; RL EMBO Rep. 17:1155-1168(2016). RN [39] RP INTERACTION WITH COXSACKIEVIRUS A16 PROTEASE 3C (MICROBIAL INFECTION), AND RP INTERACTION WITH HUMAN ENTEROVIRUS D68 PROTEASE 3C (MICROBIAL INFECTION). RX PubMed=28424289; DOI=10.1128/jvi.00546-17; RA Rui Y., Su J., Wang H., Chang J., Wang S., Zheng W., Cai Y., Wei W., RA Gordy J.T., Markham R., Kong W., Zhang W., Yu X.F.; RT "Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of RT Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68."; RL J. Virol. 91:0-0(2017). RN [40] RP FUNCTION, AND UBIQUITINATION BY TRIM40. RX PubMed=29117565; DOI=10.1016/j.celrep.2017.10.020; RA Zhao C., Jia M., Song H., Yu Z., Wang W., Li Q., Zhang L., Zhao W., Cao X.; RT "The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by RT Targeting MDA5 and RIG-I."; RL Cell Rep. 21:1613-1623(2017). RN [41] RP FUNCTION, AND UBIQUITINATION BY TRIM65. RX PubMed=28594402; DOI=10.1038/cddis.2017.257; RA Meng J., Yao Z., He Y., Zhang R., Zhang Y., Yao X., Yang H., Chen L., RA Zhang Z., Zhang H., Bao X., Hu G., Wu T., Cheng J.; RT "ARRDC4 regulates enterovirus 71-induced innate immune response by RT promoting K63 polyubiquitination of MDA5 through TRIM65."; RL Cell Death Dis. 8:e2866-e2866(2017). RN [42] RP INTERACTION WITH ENCEPHALOMYOCARDITIS VIRUS PROTEIN 2C (MICROBIAL RP INFECTION). RX PubMed=30312637; DOI=10.1016/j.antiviral.2018.10.010; RA Li L., Fan H., Song Z., Liu X., Bai J., Jiang P.; RT "Encephalomyocarditis virus 2C protein antagonizes interferon-beta RT signaling pathway through interaction with MDA5."; RL Antiviral Res. 161:70-84(2018). RN [43] RP INTERACTION WITH ZCCHC3, AND UBIQUITINATION. RX PubMed=30193849; DOI=10.1016/j.immuni.2018.08.014; RA Lian H., Zang R., Wei J., Ye W., Hu M.M., Chen Y.D., Zhang X.N., Guo Y., RA Lei C.Q., Yang Q., Luo W.W., Li S., Shu H.B.; RT "The zinc-finger protein ZCCHC3 binds RNA and facilitates viral RNA sensing RT and activation of the RIG-I-like receptors."; RL Immunity 49:438-448(2018). RN [44] RP FUNCTION, INTERACTION WITH IFIH1, AND SUBCELLULAR LOCATION. RX PubMed=32169843; DOI=10.4049/jimmunol.1900667; RA Wu X.M., Zhang J., Li P.W., Hu Y.W., Cao L., Ouyang S., Bi Y.H., Nie P., RA Chang M.X.; RT "NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the RT Interaction of MDA5 and MAVS."; RL J. Immunol. 204:2216-2231(2020). RN [45] 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 [46] RP FUNCTION. RX PubMed=33514628; DOI=10.1128/jvi.02415-20; RA Rebendenne A., Valadao A.L.C., Tauziet M., Maarifi G., Bonaventure B., RA McKellar J., Planes R., Nisole S., Arnaud-Arnould M., Moncorge O., RA Goujon C.; RT "SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable RT to control replication in lung epithelial cells."; RL J. Virol. 0:0-0(2021). RN [47] RP ISGYLATION AT LYS-23 AND LYS-43, INTERACTION WITH SARS-COV-2 VIRUS PROTEIN RP NSP3 (MICROBIAL INFECTION), FUNCTION, MUTAGENESIS OF LYS-23; LYS-43; RP LYS-68; 74-GLY-TRP-75; SER-88; 841-ILE-GLU-842 AND 848-ASP-PHE-849, RP SUBUNIT, PHOSPHORYLATION AT SER-88, AND SUBCELLULAR LOCATION. RX PubMed=33727702; DOI=10.1038/s41564-021-00884-1; RA Liu G., Lee J.H., Parker Z.M., Acharya D., Chiang J.J., van Gent M., RA Riedl W., Davis-Gardner M.E., Wies E., Chiang C., Gack M.U.; RT "ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS- RT CoV-2 papain-like protease to evade host innate immunity."; RL Nat. Microbiol. 6:467-478(2021). RN [48] RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 893-1017 IN COMPLEX WITH ZINC RP IONS. RX PubMed=19531363; DOI=10.1016/j.abb.2009.06.008; RA Li X., Lu C., Stewart M., Xu H., Strong R.K., Igumenova T., Li P.; RT "Structural basis of double-stranded RNA recognition by the RIG-I like RT receptor MDA5."; RL Arch. Biochem. Biophys. 488:23-33(2009). RN [49] RP STRUCTURE BY NMR OF 896-1025 IN COMPLEX WITH ZINC IONS. 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 [50] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 277-490. RG Structural genomics consortium (SGC); RT "Human dech-box RNA helicase mda5 (melanoma differentiation-associated RT protein 5), dech-domain."; RL Submitted (FEB-2009) to the PDB data bank. RN [51] RP VARIANT THR-946, AND POSSIBLE ASSOCIATION WITH T1D19. RX PubMed=16699517; DOI=10.1038/ng1800; RA Smyth D.J., Cooper J.D., Bailey R., Field S., Burren O., Smink L.J., RA Guja C., Ionescu-Tirgoviste C., Widmer B., Dunger D.B., Savage D.A., RA Walker N.M., Clayton D.G., Todd J.A.; RT "A genome-wide association study of nonsynonymous SNPs identifies a type 1 RT diabetes locus in the interferon-induced helicase (IFIH1) region."; RL Nat. Genet. 38:617-619(2006). RN [52] RP INVOLVEMENT IN AGS7, VARIANTS AGS7 PHE-372; THR-452 AND HIS-779, AND RP CHARACTERIZATION OF VARIANTS AGS7 PHE-372; THR-452 AND HIS-779. RX PubMed=24995871; DOI=10.1016/j.ajhg.2014.06.007; RA Oda H., Nakagawa K., Abe J., Awaya T., Funabiki M., Hijikata A., RA Nishikomori R., Funatsuka M., Ohshima Y., Sugawara Y., Yasumi T., Kato H., RA Shirai T., Ohara O., Fujita T., Heike T.; RT "Aicardi-Goutieres syndrome is caused by IFIH1 mutations."; RL Am. J. Hum. Genet. 95:121-125(2014). RN [53] RP INVOLVEMENT IN AGS7, VARIANTS AGS7 GLY-337; VAL-393; ARG-495; GLN-720; RP HIS-779 AND CYS-779, AND CHARACTERIZATION OF VARIANTS AGS7 GLY-337; RP VAL-393; ARG-495; GLN-720; HIS-779 AND CYS-779. RX PubMed=24686847; DOI=10.1038/ng.2933; RA Rice G.I., del Toro Duany Y., Jenkinson E.M., Forte G.M., Anderson B.H., RA Ariaudo G., Bader-Meunier B., Baildam E.M., Battini R., Beresford M.W., RA Casarano M., Chouchane M., Cimaz R., Collins A.E., Cordeiro N.J., RA Dale R.C., Davidson J.E., De Waele L., Desguerre I., Faivre L., Fazzi E., RA Isidor B., Lagae L., Latchman A.R., Lebon P., Li C., Livingston J.H., RA Lourenco C.M., Mancardi M.M., Masurel-Paulet A., McInnes I.B., RA Menezes M.P., Mignot C., O'Sullivan J., Orcesi S., Picco P.P., Riva E., RA Robinson R.A., Rodriguez D., Salvatici E., Scott C., Szybowska M., RA Tolmie J.L., Vanderver A., Vanhulle C., Vieira J.P., Webb K., Whitney R.N., RA Williams S.G., Wolfe L.A., Zuberi S.M., Hur S., Crow Y.J.; RT "Gain-of-function mutations in IFIH1 cause a spectrum of human disease RT phenotypes associated with upregulated type I interferon signaling."; RL Nat. Genet. 46:503-509(2014). RN [54] RP INVOLVEMENT IN SGMRT1, VARIANT SGMRT1 GLN-822, AND CHARACTERIZATION OF RP VARIANT SGMRT1 GLN-822. RX PubMed=25620204; DOI=10.1016/j.ajhg.2014.12.014; RA Rutsch F., MacDougall M., Lu C., Buers I., Mamaeva O., Nitschke Y., RA Rice G.I., Erlandsen H., Kehl H.G., Thiele H., Nurnberg P., Hohne W., RA Crow Y.J., Feigenbaum A., Hennekam R.C.; RT "A specific IFIH1 gain-of-function mutation causes Singleton-Merten RT syndrome."; RL Am. J. Hum. Genet. 96:275-282(2015). RN [55] RP VARIANT IMD95 GLU-365, CHARACTERIZATION OF VARIANT IMD95 GLU-365, FUNCTION, RP AND INVOLVEMENT IN IMD95. RX PubMed=28606988; DOI=10.1084/jem.20161759; RA Lamborn I.T., Jing H., Zhang Y., Drutman S.B., Abbott J.K., Munir S., RA Bade S., Murdock H.M., Santos C.P., Brock L.G., Masutani E., Fordjour E.Y., RA McElwee J.J., Hughes J.D., Nichols D.P., Belkadi A., Oler A.J., RA Happel C.S., Matthews H.F., Abel L., Collins P.L., Subbarao K., RA Gelfand E.W., Ciancanelli M.J., Casanova J.L., Su H.C.; RT "Recurrent rhinovirus infections in a child with inherited MDA5 RT deficiency."; RL J. Exp. Med. 214:1949-1972(2017). RN [56] RP VARIANT IMD95 889-LYS--ASP-1025 DEL, AND CHARACTERIZATION OF VARIANT IMD95 RP 889-LYS--ASP-1025 DEL. RX PubMed=29018476; DOI=10.3389/fgene.2017.00130; RA Zaki M., Thoenes M., Kawalia A., Nuernberg P., Kaiser R., Heller R., RA Bolz H.J.; RT "Recurrent and prolonged infections in a child with a homozygous IFIH1 RT nonsense mutation."; RL Front. Genet. 8:130-130(2017). CC -!- FUNCTION: Innate immune receptor which acts as a cytoplasmic sensor of CC viral nucleic acids and plays a major role in sensing viral infection CC and in the activation of a cascade of antiviral responses including the CC induction of type I interferons and pro-inflammatory cytokines CC (PubMed:32169843, PubMed:33727702, PubMed:28594402). Its ligands CC include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA CC (>1 kb in length) (PubMed:22160685). Upon ligand binding it associates CC with mitochondria antiviral signaling protein (MAVS/IPS1) which CC activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate CC interferon regulatory factors: IRF3 and IRF7 which in turn activate CC transcription of antiviral immunological genes, including interferons CC (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the CC Picornaviridae family members such as encephalomyocarditis virus CC (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus CC (PubMed:28606988). Detects coronavirus SARS-CoV-2 (PubMed:33440148, CC PubMed:33514628). Can also detect other viruses such as dengue virus CC (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral CC signaling in response to viruses containing a dsDNA genome, such as CC vaccinia virus. Plays an important role in amplifying innate immune CC signaling through recognition of RNA metabolites that are produced CC during virus infection by ribonuclease L (RNase L). May play an CC important role in enhancing natural killer cell function and may be CC involved in growth inhibition and apoptosis in several tumor cell CC lines. {ECO:0000269|PubMed:14645903, ECO:0000269|PubMed:19211564, CC ECO:0000269|PubMed:19656871, ECO:0000269|PubMed:21217758, CC ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:22160685, CC ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:28606988, CC ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:33440148, CC ECO:0000269|PubMed:33514628, ECO:0000269|PubMed:33727702}. 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:22160685}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000305|PubMed:19211564, ECO:0000305|PubMed:22160685}; CC -!- SUBUNIT: Monomer in the absence of ligands and homodimerizes in the CC presence of dsRNA ligands. Can assemble into helical or linear CC polymeric filaments on long dsRNA (PubMed:33727702). Interacts with CC MAVS/IPS1. Interacts (via the CARD domains) with TKFC, the interaction CC is inhibited by viral infection (PubMed:17600090). Interacts with CC PCBP2. Interacts with NLRC5. Interacts with PIAS2-beta. Interacts with CC DDX60. Interacts with ANKRD17. Interacts with IKBKE (PubMed:17600090). CC Interacts with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as CC ATG12-ATG5 conjugates (PubMed:17709747). Interacts with ZCCHC3; leading CC to activate IFIH1/MDA5 (PubMed:30193849). Interacts with RNF123 CC (PubMed:27312109). Interacts with DDX3X (PubMed:20127681). Interacts CC with NOD1; this interaction promotes transcription of antiviral genes CC and inhibition of viral replication (PubMed:32169843). Interacts with CC ECSIT; this interaction bridges IFIH1 to the MAVS complex at the CC mitochondrion (PubMed:25228397). {ECO:0000269|PubMed:15563593, CC ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16177806, CC ECO:0000269|PubMed:17600090, ECO:0000269|PubMed:17709747, CC ECO:0000269|PubMed:19380577, ECO:0000269|PubMed:19531363, CC ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20127681, CC ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:21156324, CC ECO:0000269|PubMed:21791617, ECO:0000269|PubMed:22160685, CC ECO:0000269|PubMed:23711367, ECO:0000269|PubMed:27312109, CC ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:33727702}. CC -!- SUBUNIT: (Microbial infection) Interacts with V protein of CC paramyxoviruses; these interactions prevent IFN-beta induction, and CC subsequent establishment of an antiviral state. CC {ECO:0000269|PubMed:15563593}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC protein US11; this interaction prevents the interaction of MAVS/IPS1 to CC IFIH1. {ECO:0000269|PubMed:22301138}. CC -!- SUBUNIT: (Microbial infection) Interacts with Encephalomyocarditis CC virus protein 2C; this interaction inhibits the induction of the IFN- CC beta signal pathway. {ECO:0000269|PubMed:30312637}. CC -!- SUBUNIT: (Microbial infection) Interacts with protease 3C of CC coxsackievirus A16; this interaction inhibits IFIH1 thereby attenuating CC type-I IFN production. {ECO:0000269|PubMed:28424289}. CC -!- SUBUNIT: (Microbial infection) Interacts with SARS-COV-2 virus protein CC NSP3; the interaction antagonizes ISG15-dependent IFIH1 activation via CC active de-ISGylation. {ECO:0000269|PubMed:33727702}. CC -!- INTERACTION: CC Q9BYX4; Q9BYX4: IFIH1; NbExp=6; IntAct=EBI-6115771, EBI-6115771; CC Q9BYX4; Q14164: IKBKE; NbExp=2; IntAct=EBI-6115771, EBI-307369; CC Q9BYX4; P05161: ISG15; NbExp=7; IntAct=EBI-6115771, EBI-746466; CC Q9BYX4; Q14145: KEAP1; NbExp=3; IntAct=EBI-6115771, EBI-751001; CC Q9BYX4; Q7Z434: MAVS; NbExp=7; IntAct=EBI-6115771, EBI-995373; CC Q9BYX4; Q7Z434-1: MAVS; NbExp=3; IntAct=EBI-6115771, EBI-15577799; CC Q9BYX4; O75569: PRKRA; NbExp=4; IntAct=EBI-6115771, EBI-713955; CC Q9BYX4; O14730: RIOK3; NbExp=6; IntAct=EBI-6115771, EBI-1047061; CC Q9BYX4; Q96EQ8: RNF125; NbExp=2; IntAct=EBI-6115771, EBI-2339208; CC Q9BYX4; Q3LXA3: TKFC; NbExp=5; IntAct=EBI-6115771, EBI-4291069; CC Q9BYX4; P0DTC5: M; Xeno; NbExp=3; IntAct=EBI-6115771, EBI-25475853; CC Q9BYX4; P0C774: P/V; Xeno; NbExp=3; IntAct=EBI-6115771, EBI-3650423; CC Q9BYX4; P11207: P/V; Xeno; NbExp=3; IntAct=EBI-6115771, EBI-6148694; CC Q9BYX4; P30927: P/V; Xeno; NbExp=2; IntAct=EBI-6115771, EBI-6599165; CC Q9BYX4; Q9EMA9: P/V; Xeno; NbExp=2; IntAct=EBI-6115771, EBI-6598728; CC Q9BYX4; PRO_0000449621 [P0DTD1]: rep; Xeno; NbExp=2; IntAct=EBI-6115771, EBI-25492388; CC Q9BYX4; P04487: US11; Xeno; NbExp=4; IntAct=EBI-6115771, EBI-6150681; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11805321, CC ECO:0000269|PubMed:14645903, ECO:0000269|PubMed:32169843, CC ECO:0000269|PubMed:33727702}. Nucleus {ECO:0000305}. Mitochondrion CC {ECO:0000269|PubMed:33727702}. Note=Upon viral RNA stimulation and CC ISGylation, translocates from cytosol to mitochondrion. May be found in CC the nucleus, during apoptosis. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BYX4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BYX4-2; Sequence=VSP_013337, VSP_013338; CC -!- TISSUE SPECIFICITY: Widely expressed, at a low level. Expression is CC detected at slightly highest levels in placenta, pancreas and spleen CC and at barely levels in detectable brain, testis and lung. CC {ECO:0000269|PubMed:11805321, ECO:0000269|PubMed:12015121, CC ECO:0000269|PubMed:14645903}. CC -!- INDUCTION: By interferon (IFN) and TNF. {ECO:0000269|PubMed:11805321}. CC -!- PTM: Sumoylated. Sumoylation positively regulates its role in type I CC interferon induction and is enhanced by PIAS2-beta. CC {ECO:0000269|PubMed:21156324}. CC -!- PTM: Ubiquitinated by RNF125, leading to its degradation by the CC proteasome (PubMed:17460044). USP17/UPS17L2-dependent deubiquitination CC positively regulates the receptor (PubMed:20368735). Ubiquitinated by CC TRIM25 via 'Lys-63'-linked ubiquitination, promoting activation of CC IFIH1/MDA5 (PubMed:30193849). Ubiquitinated by TRIM40 via 'Lys-48'- CC linked ubiquitination; leading to proteasomal degradation CC (PubMed:29117565). Ubiquitinated by TRIM65 via 'Lys-63'-linked CC ubiquitination, promoting activation of IFIH1/MDA5 (PubMed:28594402). CC {ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:20368735, CC ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:29117565, CC ECO:0000269|PubMed:30193849}. CC -!- PTM: ISGylated by ISG15. ISGylation increases upon infection with CC dengue (DENV) or Zika (ZIKV) viruses. ISGylation at Lys-23 and Lys-43 CC is dependent of dephosphorylation at Ser-88, regulates mitochondrial CC translocation and oligomerization. Essential for IFIH1/MDA5-mediated CC cytokine responses and restriction of virus replication. CC {ECO:0000269|PubMed:33727702}. CC -!- PTM: Phosphorylated at Ser-88. Dephosphorylated by phsophatases PP1; CC dephosphorylation precedes and is required for ISGylation. CC {ECO:0000269|PubMed:33727702}. CC -!- PTM: During apoptosis, processed into 3 cleavage products. The CC helicase-containing fragment, once liberated from the CARD domains, CC translocate from the cytoplasm to the nucleus. The processed protein CC significantly sensitizes cells to DNA degradation. CC {ECO:0000250|UniProtKB:Q8R5F7}. CC -!- PTM: (Microbial infection) Cleaved and inactivated by the protease 2A CC of coxsackievirus B3, poliovirus and enterovirus 71 allowing the virus CC to disrupt the host type I interferon production. CC {ECO:0000269|PubMed:24390337}. CC -!- DISEASE: Type 1 diabetes mellitus 19 (T1D19) [MIM:610155]: A CC multifactorial disorder of glucose homeostasis that is characterized by CC susceptibility to ketoacidosis in the absence of insulin therapy. CC Clinical features are polydipsia, polyphagia and polyuria which result CC from hyperglycemia-induced osmotic diuresis and secondary thirst. These CC derangements result in long-term complications that affect the eyes, CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:16699517}. CC Note=Disease susceptibility may be associated with variants affecting CC the gene represented in this entry. CC -!- DISEASE: Note=IFIH1 is the CADM-140 autoantigen, involved in clinically CC amyopathic dermatomyositis (CADM). This is a chronic inflammatory CC disorder that shows typical skin manifestations of dermatomyositis but CC has no or little evidence of clinical myositis. Anti-CADM-140 CC antibodies appear to be specific to dermatomyositis, especially CADM. CC Patients with anti-CADM-140 antibodies frequently develop life- CC threatening acute progressive interstitial lung disease (ILD). CC {ECO:0000269|PubMed:19565506, ECO:0000269|PubMed:20015976}. CC -!- DISEASE: Aicardi-Goutieres syndrome 7 (AGS7) [MIM:615846]: A form of CC Aicardi-Goutieres syndrome, a genetically heterogeneous disease CC characterized by cerebral atrophy, leukoencephalopathy, intracranial CC calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, CC increased CSF alpha-interferon, and negative serologic investigations CC for common prenatal infection. Clinical features as thrombocytopenia, CC hepatosplenomegaly and elevated hepatic transaminases along with CC intermittent fever may erroneously suggest an infective process. Severe CC neurological dysfunctions manifest in infancy as progressive CC microcephaly, spasticity, dystonic posturing and profound psychomotor CC retardation. Death often occurs in early childhood. CC {ECO:0000269|PubMed:24686847, ECO:0000269|PubMed:24995871}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Singleton-Merten syndrome 1 (SGMRT1) [MIM:182250]: An CC autosomal dominant disorder with variable expression. Core features are CC marked aortic calcification, dental anomalies, osteopenia, acro- CC osteolysis, and to a lesser extent glaucoma, psoriasis, muscle CC weakness, and joint laxity. Dental anomalies include delayed eruption CC and immature root formation of anterior permanent teeth, early loss of CC permanent teeth due to short roots, acute root resorption, high caries, CC and aggressive alveolar bone loss. Additional clinical manifestations CC include particular facial characteristics and abnormal joint and muscle CC ligaments. {ECO:0000269|PubMed:25620204}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Immunodeficiency 95 (IMD95) [MIM:619773]: An autosomal CC recessive disorder characterized by the onset of recurrent and severe CC viral respiratory infections in infancy or early childhood, and CC impaired interferon production during viral infection. CC {ECO:0000269|PubMed:28606988, ECO:0000269|PubMed:29018476}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: In HIV-1 infected HeLa-CD4 cells, overexpression of CC IFIH1 results in a great increase in the level of secreted viral p24 CC protein. CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH78180.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAB71141.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AF095844; AAG34368.1; -; mRNA. DR EMBL; AY017378; AAG54076.1; -; mRNA. DR EMBL; BC046208; AAH46208.1; -; mRNA. DR EMBL; BC078180; AAH78180.1; ALT_SEQ; mRNA. DR EMBL; BC111750; AAI11751.1; -; mRNA. DR EMBL; AK056293; BAB71141.1; ALT_INIT; mRNA. DR CCDS; CCDS2217.1; -. [Q9BYX4-1] DR RefSeq; NP_071451.2; NM_022168.3. [Q9BYX4-1] DR PDB; 2RQB; NMR; -; A=896-1025. DR PDB; 3B6E; X-ray; 1.60 A; A=277-490. DR PDB; 3GA3; X-ray; 1.45 A; A=893-1017. DR PDB; 4GL2; X-ray; 3.56 A; A/B=306-1017. DR PDB; 7DNI; EM; 3.20 A; A/B/C/D=1-208. DR PDB; 7DNJ; EM; 3.30 A; A/B/C/D=1-208. DR PDB; 7JL0; EM; 4.30 A; A=287-1025. DR PDB; 7JL2; EM; 4.30 A; A/C/E=287-1025. DR PDBsum; 2RQB; -. DR PDBsum; 3B6E; -. DR PDBsum; 3GA3; -. DR PDBsum; 4GL2; -. DR PDBsum; 7DNI; -. DR PDBsum; 7DNJ; -. DR PDBsum; 7JL0; -. DR PDBsum; 7JL2; -. DR AlphaFoldDB; Q9BYX4; -. DR EMDB; EMD-22368; -. DR EMDB; EMD-22370; -. DR EMDB; EMD-30784; -. DR EMDB; EMD-30785; -. DR SMR; Q9BYX4; -. DR BioGRID; 122082; 44. DR DIP; DIP-42607N; -. DR IntAct; Q9BYX4; 58. DR STRING; 9606.ENSP00000497271; -. DR ChEMBL; CHEMBL4739862; -. DR iPTMnet; Q9BYX4; -. DR PhosphoSitePlus; Q9BYX4; -. DR BioMuta; IFIH1; -. DR DMDM; 134047802; -. DR EPD; Q9BYX4; -. DR jPOST; Q9BYX4; -. DR MassIVE; Q9BYX4; -. DR MaxQB; Q9BYX4; -. DR PaxDb; 9606-ENSP00000263642; -. DR PeptideAtlas; Q9BYX4; -. DR ProteomicsDB; 79740; -. [Q9BYX4-1] DR ProteomicsDB; 79741; -. [Q9BYX4-2] DR Pumba; Q9BYX4; -. DR Antibodypedia; 805; 567 antibodies from 42 providers. DR DNASU; 64135; -. DR Ensembl; ENST00000421365.2; ENSP00000408450.2; ENSG00000115267.10. [Q9BYX4-2] DR Ensembl; ENST00000649979.2; ENSP00000497271.1; ENSG00000115267.10. [Q9BYX4-1] DR GeneID; 64135; -. DR KEGG; hsa:64135; -. DR MANE-Select; ENST00000649979.2; ENSP00000497271.1; NM_022168.4; NP_071451.2. DR UCSC; uc002uce.5; human. [Q9BYX4-1] DR AGR; HGNC:18873; -. DR CTD; 64135; -. DR DisGeNET; 64135; -. DR GeneCards; IFIH1; -. DR GeneReviews; IFIH1; -. DR HGNC; HGNC:18873; IFIH1. DR HPA; ENSG00000115267; Tissue enhanced (bone). DR MalaCards; IFIH1; -. DR MIM; 182250; phenotype. DR MIM; 606951; gene. DR MIM; 610155; phenotype. DR MIM; 615846; phenotype. DR MIM; 619773; phenotype. DR neXtProt; NX_Q9BYX4; -. DR OpenTargets; ENSG00000115267; -. DR Orphanet; 51; Aicardi-Goutieres syndrome. DR Orphanet; 85191; Singleton-Merten dysplasia. DR PharmGKB; PA134889215; -. DR VEuPathDB; HostDB:ENSG00000115267; -. DR eggNOG; KOG0354; Eukaryota. DR GeneTree; ENSGT00940000153173; -. DR HOGENOM; CLU_006888_0_0_1; -. DR InParanoid; Q9BYX4; -. DR OMA; TFCQMNP; -. DR OrthoDB; 342391at2759; -. DR PhylomeDB; Q9BYX4; -. DR TreeFam; TF330258; -. DR PathwayCommons; Q9BYX4; -. DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation. DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10. DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling. DR Reactome; R-HSA-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; Q9BYX4; -. DR SIGNOR; Q9BYX4; -. DR BioGRID-ORCS; 64135; 9 hits in 1158 CRISPR screens. DR ChiTaRS; IFIH1; human. DR EvolutionaryTrace; Q9BYX4; -. DR GeneWiki; MDA5; -. DR GenomeRNAi; 64135; -. DR Pharos; Q9BYX4; Tbio. DR PRO; PR:Q9BYX4; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9BYX4; Protein. DR Bgee; ENSG00000115267; Expressed in palpebral conjunctiva and 195 other cell types or tissues. DR ExpressionAtlas; Q9BYX4; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. 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:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProt. DR GO; GO:0043021; F:ribonucleoprotein complex binding; IPI:UniProtKB. DR GO; GO:0003723; F: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:0071360; P:cellular response to exogenous dsRNA; IMP:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IEP:ARUK-UCL. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0009597; P:detection of virus; TAS:BHF-UCL. DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB. DR GO; GO:0039530; P:MDA-5 signaling pathway; IDA:UniProtKB. DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IMP:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB. DR GO; GO:0060760; P:positive regulation of response to cytokine stimulus; IMP:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IEA:Ensembl. DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB. DR GO; GO:0034344; P:regulation of type III interferon production; TAS:UniProtKB. DR GO; GO:0009615; P:response to virus; IDA:UniProtKB. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IEA:Ensembl. DR CDD; cd08818; CARD_MDA5_r1; 1. DR CDD; cd08819; CARD_MDA5_r2; 1. DR CDD; cd18074; DEXHc_RLR-2; 1. DR CDD; cd15807; MDA5_C; 1. DR CDD; cd12090; MDA5_ID; 1. DR CDD; cd18802; SF2_C_dicer; 1. DR Gene3D; 1.20.1320.30; -; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 2. 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; IPR031964; CARD_dom. DR InterPro; IPR011029; DEATH-like_dom_sf. 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; HELICASE WITH DEATH DOMAIN-RELATED; 1. DR PANTHER; PTHR14074:SF14; INTERFERON-INDUCED HELICASE C DOMAIN-CONTAINING PROTEIN 1; 1. DR Pfam; PF16739; CARD_2; 2. 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; 2. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS51789; RLR_CTR; 1. DR Genevisible; Q9BYX4; HS. PE 1: Evidence at protein level; KW 3D-structure; Aicardi-Goutieres syndrome; Alternative splicing; KW Antiviral defense; ATP-binding; Cytoplasm; Diabetes mellitus; KW Disease variant; Helicase; Host-virus interaction; Hydrolase; Immunity; KW Innate immunity; Isopeptide bond; Metal-binding; Mitochondrion; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW RNA-binding; Ubl conjugation; Zinc. FT CHAIN 1..1025 FT /note="Interferon-induced helicase C domain-containing FT protein 1" FT /id="PRO_0000102012" FT DOMAIN 7..97 FT /note="CARD 1" FT DOMAIN 110..190 FT /note="CARD 2" FT DOMAIN 316..509 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 700..882 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT DOMAIN 893..1020 FT /note="RLR CTR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125" FT REGION 271..307 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 640..662 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 271..291 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 644..659 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 907 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125" FT BINDING 910 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125" FT BINDING 962 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125" FT BINDING 964 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125" FT SITE 208..209 FT /note="Cleavage" FT /evidence="ECO:0000250" FT SITE 216..217 FT /note="Cleavage" FT /evidence="ECO:0000250" FT SITE 251..252 FT /note="Cleavage" FT /evidence="ECO:0000250" FT MOD_RES 88 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:33727702" FT MOD_RES 289 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8R5F7" FT MOD_RES 291 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8R5F7" FT MOD_RES 301 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8R5F7" FT MOD_RES 645 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8R5F7" FT MOD_RES 828 FT /note="Phosphoserine; by RIOK3" FT /evidence="ECO:0000269|PubMed:25865883" FT CROSSLNK 23 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000269|PubMed:33727702" FT CROSSLNK 43 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000269|PubMed:33727702" FT VAR_SEQ 208..221 FT /note="EIENLSQVDGPQVE -> GICNFTEEDSSNSA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013337" FT VAR_SEQ 222..1025 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013338" FT VARIANT 337 FT /note="R -> G (in AGS7; enhances the interferon signaling FT pathway activation; enhances the stability of filament FT formation; enhances dsRNA binding activity; no loss of ATP FT hydrolysis; dbSNP:rs587777447)" FT /evidence="ECO:0000269|PubMed:24686847" FT /id="VAR_071375" FT VARIANT 365 FT /note="K -> E (in IMD95; does not bind the double-stranded FT RNA analog poly(I:C); loss of IFNB1 and NFKB promoter FT activation after stimulation with poly(I:C), when tested in FT a luciferase reporter assay)" FT /evidence="ECO:0000269|PubMed:28606988" FT /id="VAR_087007" FT VARIANT 372 FT /note="L -> F (in AGS7; enhances IFNB1 promoter activation; FT loss of ligand-induced responsiveness; dbSNP:rs587777576)" FT /evidence="ECO:0000269|PubMed:24995871" FT /id="VAR_071376" FT VARIANT 393 FT /note="D -> V (in AGS7; enhances the interferon signaling FT pathway activation; enhances the stability of filament FT formation; enhances dsRNA binding activity; no loss of ATP FT hydrolysis; dbSNP:rs587777449)" FT /evidence="ECO:0000269|PubMed:24686847" FT /id="VAR_071377" FT VARIANT 452 FT /note="A -> T (in AGS7; enhances IFNB1 promoter activation; FT loss of ligand-induced responsiveness; dbSNP:rs587777575)" FT /evidence="ECO:0000269|PubMed:24995871" FT /id="VAR_071378" FT VARIANT 460 FT /note="H -> R (in dbSNP:rs10930046)" FT /id="VAR_031226" FT VARIANT 495 FT /note="G -> R (in AGS7; enhances the interferon signaling FT pathway activation; enhances the stability of filament FT formation; enhances dsRNA binding activity; no loss of ATP FT hydrolysis; dbSNP:rs672601336)" FT /evidence="ECO:0000269|PubMed:24686847" FT /id="VAR_071379" FT VARIANT 720 FT /note="R -> Q (in AGS7; enhances the interferon signaling FT pathway activation; enhances the stability of filament FT formation; enhances dsRNA binding activity; no loss of ATP FT hydrolysis; dbSNP:rs587777445)" FT /evidence="ECO:0000269|PubMed:24686847" FT /id="VAR_071380" FT VARIANT 779 FT /note="R -> C (in AGS7; enhances the interferon signaling FT pathway activation; enhances the stability of filament FT formation; enhances dsRNA binding activity; no loss of ATP FT hydrolysis; dbSNP:rs587777448)" FT /evidence="ECO:0000269|PubMed:24686847" FT /id="VAR_071381" FT VARIANT 779 FT /note="R -> H (in AGS7; enhances the interferon signaling FT pathway activation; enhances the stability of filament FT formation; enhances dsRNA binding activity; enhances IFNB1 FT promoter activation; no loss of ATP hydrolysis; FT dbSNP:rs587777446)" FT /evidence="ECO:0000269|PubMed:24686847, FT ECO:0000269|PubMed:24995871" FT /id="VAR_071382" FT VARIANT 822 FT /note="R -> Q (in SGMRT1; gain-of-function mutation FT resulting in enhanced INFB1 induction; dbSNP:rs376048533)" FT /evidence="ECO:0000269|PubMed:25620204" FT /id="VAR_073666" FT VARIANT 843 FT /note="H -> R (in dbSNP:rs3747517)" FT /evidence="ECO:0000269|PubMed:14645903, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334" FT /id="VAR_021594" FT VARIANT 889..1025 FT /note="Missing (in IMD95; no protein detected by Western FT blot in homozygous patient cells)" FT /evidence="ECO:0000269|PubMed:29018476" FT /id="VAR_087008" FT VARIANT 946 FT /note="A -> T (risk factor for T1D19; dbSNP:rs1990760)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16699517" FT /id="VAR_021595" FT MUTAGEN 23 FT /note="K->A: Loss of ISGylation, loss of oligomerization, FT strongly reduced signaling activity and IFNB induction, FT loss of virus replication restriction, no effect on FT phosphorylation or RNA-binding; when associated with A-43." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 43 FT /note="K->A: Loss of ISGylation, loss of oligomerization, FT strongly reduced signaling activity and IFNB induction, FT loss of virus replication restriction, no effect on FT phosphorylation or RNA-binding; when associated with A-23." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 68 FT /note="K->A: No effect on ISGylation or signaling activity FT and IFNB induction." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 74..75 FT /note="GW->AA: Loss of oligomerization." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 88 FT /note="S->A: Increases ISGylation." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 88 FT /note="S->E,D: Loss of signaling activity and IFNB FT induction. Reduced ISGylation. Loss of virus replication FT restriction." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 251 FT /note="D->A: No cleavage and no acceleration of DNA FT degradation." FT /evidence="ECO:0000269|PubMed:12015121" FT MUTAGEN 335 FT /note="K->A: Loss of dsRNA-induced ATPase activity. No FT effect on RNA binding. Changed MDA-5 signaling pathway." FT /evidence="ECO:0000269|PubMed:19211564" FT MUTAGEN 443..446 FT /note="DECH->AACA: Loss of dsRNA-induced ATPase activity. FT No effect on RNA binding. Changed MDA-5 signaling pathway." FT /evidence="ECO:0000269|PubMed:19211564" FT MUTAGEN 444 FT /note="E->A: No acceleration of DNA degradation, no binding FT to ATP, and no helicase activity." FT /evidence="ECO:0000269|PubMed:12015121" FT MUTAGEN 488..490 FT /note="TAS->AAA: Loss of dsRNA-induced ATPase activity. No FT effect on RNA binding. Changed MDA-5 signaling pathway." FT /evidence="ECO:0000269|PubMed:19211564" FT MUTAGEN 789..793 FT /note="TTVAE->ATVAA: Loss of dsRNA-induced ATPase activity. FT Loss of MDA-5 signaling pathway." FT /evidence="ECO:0000269|PubMed:19211564" FT MUTAGEN 818..822 FT /note="QARGR->AARGA: Loss of dsRNA-induced ATPase activity. FT No effect on MDA-5 signaling pathway." FT /evidence="ECO:0000269|PubMed:19211564" FT MUTAGEN 828 FT /note="S->A: Promotes multimerization after polyI:C FT stimulation; greatly enhances signaling." FT /evidence="ECO:0000269|PubMed:25865883" FT MUTAGEN 828 FT /note="S->D: Inhibits multimerization after polyI:C FT stimulation." FT /evidence="ECO:0000269|PubMed:25865883" FT MUTAGEN 829 FT /note="T->A: Moderately increases signaling." FT /evidence="ECO:0000269|PubMed:25865883" FT MUTAGEN 841..842 FT /note="IE->RR: Loss of oligomerization." FT /evidence="ECO:0000269|PubMed:33727702" FT MUTAGEN 848..849 FT /note="DF->AA: Loss of oligomerization." FT /evidence="ECO:0000269|PubMed:33727702" FT CONFLICT 439 FT /note="L -> F (in Ref. 2; AAG54076)" FT /evidence="ECO:0000305" FT CONFLICT 475 FT /note="N -> H (in Ref. 4; BAB71141)" FT /evidence="ECO:0000305" FT CONFLICT 592 FT /note="E -> K (in Ref. 1; AAG34368)" FT /evidence="ECO:0000305" FT CONFLICT 598 FT /note="R -> S (in Ref. 2; AAG54076)" FT /evidence="ECO:0000305" FT CONFLICT 609 FT /note="E -> K (in Ref. 2; AAG54076)" FT /evidence="ECO:0000305" FT CONFLICT 782 FT /note="K -> R (in Ref. 4; BAB71141)" FT /evidence="ECO:0000305" FT HELIX 8..17 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 19..25 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 28..31 FT /evidence="ECO:0007829|PDB:7DNI" FT TURN 32..34 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 40..67 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 75..85 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 89..93 FT /evidence="ECO:0007829|PDB:7DNI" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 105..128 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 131..141 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 146..155 FT /evidence="ECO:0007829|PDB:7DNI" FT TURN 156..158 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 160..170 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 177..186 FT /evidence="ECO:0007829|PDB:7DNI" FT TURN 187..189 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 191..198 FT /evidence="ECO:0007829|PDB:7DNI" FT HELIX 293..299 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 310..320 FT /evidence="ECO:0007829|PDB:3B6E" FT STRAND 325..328 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 332..352 FT /evidence="ECO:0007829|PDB:3B6E" FT STRAND 359..365 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 366..375 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 377..381 FT /evidence="ECO:0007829|PDB:3B6E" FT TURN 382..384 FT /evidence="ECO:0007829|PDB:3B6E" FT STRAND 387..389 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 400..406 FT /evidence="ECO:0007829|PDB:3B6E" FT STRAND 408..413 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 414..422 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 434..436 FT /evidence="ECO:0007829|PDB:3B6E" FT STRAND 438..442 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 454..473 FT /evidence="ECO:0007829|PDB:3B6E" FT STRAND 483..488 FT /evidence="ECO:0007829|PDB:3B6E" FT HELIX 900..902 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 903..907 FT /evidence="ECO:0007829|PDB:3GA3" FT TURN 908..910 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 913..916 FT /evidence="ECO:0007829|PDB:3GA3" FT HELIX 917..919 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 921..923 FT /evidence="ECO:0007829|PDB:3GA3" FT TURN 924..926 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 927..929 FT /evidence="ECO:0007829|PDB:3GA3" FT HELIX 934..937 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 938..942 FT /evidence="ECO:0007829|PDB:3GA3" FT TURN 945..947 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 955..962 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 967..974 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 977..982 FT /evidence="ECO:0007829|PDB:3GA3" FT HELIX 984..986 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 987..991 FT /evidence="ECO:0007829|PDB:3GA3" FT TURN 992..995 FT /evidence="ECO:0007829|PDB:3GA3" FT STRAND 996..998 FT /evidence="ECO:0007829|PDB:3GA3" FT HELIX 1003..1005 FT /evidence="ECO:0007829|PDB:3GA3" FT HELIX 1015..1017 FT /evidence="ECO:0007829|PDB:3GA3" SQ SEQUENCE 1025 AA; 116689 MW; 789CFB4824B92DC9 CRC64; MSNGYSTDEN FRYLISCFRA RVKMYIQVEP VLDYLTFLPA EVKEQIQRTV ATSGNMQAVE LLLSTLEKGV WHLGWTREFV EALRRTGSPL AARYMNPELT DLPSPSFENA HDEYLQLLNL LQPTLVDKLL VRDVLDKCME EELLTIEDRN RIAAAENNGN ESGVRELLKR IVQKENWFSA FLNVLRQTGN NELVQELTGS DCSESNAEIE NLSQVDGPQV EEQLLSTTVQ PNLEKEVWGM ENNSSESSFA DSSVVSESDT SLAEGSVSCL DESLGHNSNM GSDSGTMGSD SDEENVAARA SPEPELQLRP YQMEVAQPAL EGKNIIICLP TGSGKTRVAV YIAKDHLDKK KKASEPGKVI VLVNKVLLVE QLFRKEFQPF LKKWYRVIGL SGDTQLKISF PEVVKSCDII ISTAQILENS LLNLENGEDA GVQLSDFSLI IIDECHHTNK EAVYNNIMRH YLMQKLKNNR LKKENKPVIP LPQILGLTAS PGVGGATKQA KAEEHILKLC ANLDAFTIKT VKENLDQLKN QIQEPCKKFA IADATREDPF KEKLLEIMTR IQTYCQMSPM SDFGTQPYEQ WAIQMEKKAA KEGNRKERVC AEHLRKYNEA LQINDTIRMI DAYTHLETFY NEEKDKKFAV IEDDSDEGGD DEYCDGDEDE DDLKKPLKLD ETDRFLMTLF FENNKMLKRL AENPEYENEK LTKLRNTIME QYTRTEESAR GIIFTKTRQS AYALSQWITE NEKFAEVGVK AHHLIGAGHS SEFKPMTQNE QKEVISKFRT GKINLLIATT VAEEGLDIKE CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVAHSGSGV IEHETVNDFR EKMMYKAIHC VQNMKPEEYA HKILELQMQS IMEKKMKTKR NIAKHYKNNP SLITFLCKNC SVLACSGEDI HVIEKMHHVN MTPEFKELYI VRENKALQKK CADYQINGEI ICKCGQAWGT MMVHKGLDLP CLKIRNFVVV FKNNSTKKQY KKWVELPITF PNLDYSECCL FSDED //