IFIH1_HUMAN
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 03-AUG-2022, entry version 189.
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, ECO:0000303|PubMed:33727702},
GN 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 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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
RP VARIANT THR-946, AND POSSIBLE ASSOCIATION WITH IDDM19.
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 [50]
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 [51]
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 [52]
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).
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). Its ligands include mRNA lacking
CC 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length)
CC (PubMed:22160685). Upon ligand binding it associates with mitochondria
CC antiviral signaling protein (MAVS/IPS1) which activates the IKK-related
CC kinases: TBK1 and IKBKE which phosphorylate interferon regulatory
CC factors: IRF3 and IRF7 which in turn activate transcription of
CC antiviral immunological genes, including interferons (IFNs); IFN-alpha
CC and IFN-beta. Responsible for detecting the Picornaviridae family
CC members such as encephalomyocarditis virus (EMCV) and mengo
CC encephalomyocarditis virus (ENMG). Detects coronavirus SARS-CoV-2
CC (PubMed:33440148, PubMed:33514628). Can also detect other viruses such
CC as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also
CC involved in antiviral signaling in response to viruses containing a
CC dsDNA genome, such as vaccinia virus. Plays an important role in
CC amplifying innate immune signaling through recognition of RNA
CC metabolites that are produced during virus infection by ribonuclease L
CC (RNase L). May play an important role in enhancing natural killer cell
CC function and may be involved in growth inhibition and apoptosis in
CC several tumor cell lines. {ECO:0000269|PubMed:14645903,
CC ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19656871,
CC ECO:0000269|PubMed:21217758, ECO:0000269|PubMed:21742966,
CC ECO:0000269|PubMed:22160685, ECO:0000269|PubMed:29117565,
CC ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:33514628,
CC 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).
CC {ECO:0000269|PubMed:15563593, ECO:0000269|PubMed:16127453,
CC ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:17600090,
CC ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:19380577,
CC ECO:0000269|PubMed:19531363, ECO:0000269|PubMed:19881509,
CC ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20434986,
CC ECO:0000269|PubMed:21156324, ECO:0000269|PubMed:21791617,
CC ECO:0000269|PubMed:22160685, ECO:0000269|PubMed:23711367,
CC ECO:0000269|PubMed:27312109, ECO:0000269|PubMed:30193849,
CC 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). {ECO:0000269|PubMed:17460044,
CC ECO:0000269|PubMed:20368735, 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: Diabetes mellitus, insulin-dependent, 19 (IDDM19)
CC [MIM:610155]: A multifactorial disorder of glucose homeostasis that is
CC characterized by susceptibility to ketoacidosis in the absence of
CC insulin therapy. Clinical features are polydipsia, polyphagia and
CC polyuria which result from hyperglycemia-induced osmotic diuresis and
CC secondary thirst. These derangements result in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:16699517}. Note=Disease susceptibility may be
CC associated with variants affecting 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 -!- 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};
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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 SMR; Q9BYX4; -.
DR BioGRID; 122082; 40.
DR DIP; DIP-42607N; -.
DR IntAct; Q9BYX4; 57.
DR STRING; 9606.ENSP00000263642; -.
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; Q9BYX4; -.
DR PeptideAtlas; Q9BYX4; -.
DR PRIDE; Q9BYX4; -.
DR ProteomicsDB; 79740; -. [Q9BYX4-1]
DR ProteomicsDB; 79741; -. [Q9BYX4-2]
DR Antibodypedia; 805; 514 antibodies from 42 providers.
DR DNASU; 64135; -.
DR Ensembl; ENST00000421365.2; ENSP00000408450.2; ENSG00000115267.9. [Q9BYX4-2]
DR Ensembl; ENST00000649979.2; ENSP00000497271.1; ENSG00000115267.9. [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 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 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; IQTFCQM; -.
DR OrthoDB; 1337630at2759; -.
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-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; Q9BYX4; -.
DR SIGNOR; Q9BYX4; -.
DR BioGRID-ORCS; 64135; 9 hits in 1080 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 193 other tissues.
DR ExpressionAtlas; Q9BYX4; baseline and differential.
DR Genevisible; Q9BYX4; HS.
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: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:0071360; P:cellular response to exogenous dsRNA; IMP:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; IEP:ARUK-UCL.
DR GO; GO:0039528; P:cytoplasmic pattern recognition receptor signaling pathway in response to virus; 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; IBA:GO_Central.
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: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 Gene3D; 1.10.533.10; -; 2.
DR Gene3D; 2.170.150.30; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
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_C.
DR InterPro; IPR038557; RLR_C_sf.
DR InterPro; IPR021673; RLR_CTR.
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; SSF52540; 2.
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; 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 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 946
FT /note="A -> T (associated with susceptibility to IDDM19;
FT 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
