ID IFIH1_MOUSE Reviewed; 1025 AA. AC Q8R5F7; A2AUY7; Q3U6S2; Q68EM4; Q8BYC9; Q8BZ01; Q8K5C7; Q8R144; Q8VE79; AC Q99KS4; Q9D2Z5; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 27-MAR-2024, entry version 176. DE RecName: Full=Interferon-induced helicase C domain-containing protein 1; DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9BYX4}; 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=RIG-I-like receptor 2; DE Short=RLR-2; GN Name=Ifih1 {ECO:0000312|MGI:MGI:1918836}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CLEAVAGE SITES, RP SUBCELLULAR LOCATION, 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 [2] 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Cecum, Thymus, and Vagina; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=FVB/N; TISSUE=Mammary gland; 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 [7] RP FUNCTION. RX PubMed=16625202; DOI=10.1038/nature04734; RA Kato H., Takeuchi O., Sato S., Yoneyama M., Yamamoto M., Matsui K., RA Uematsu S., Jung A., Kawai T., Ishii K.J., Yamaguchi O., Otsu K., RA Tsujimura T., Koh C.S., Reis e Sousa C., Matsuura Y., Fujita T., Akira S.; RT "Differential roles of MDA5 and RIG-I helicases in the recognition of RNA RT viruses."; RL Nature 441:101-105(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-645 AND SER-648, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [9] RP FUNCTION. RX PubMed=17942531; DOI=10.1128/jvi.01080-07; RA Loo Y.M., Fornek J., Crochet N., Bajwa G., Perwitasari O., RA Martinez-Sobrido L., Akira S., Gill M.A., Garcia-Sastre A., Katze M.G., RA Gale M. Jr.; RT "Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity."; RL J. Virol. 82:335-345(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [11] 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289; SER-291; SER-302; RP SER-645 AND SER-648, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 545-697, AND SUBUNIT. RX PubMed=22314235; DOI=10.1038/emboj.2012.19; RA Berke I.C., Modis Y.; RT "MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding RT double-stranded RNA."; RL EMBO J. 31:1714-1726(2012). 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. Its CC ligands include mRNA lacking 2'-O-methylation at their 5' cap and long- CC dsRNA (>1 kb in length). Upon ligand binding it associates with CC mitochondria antiviral signaling protein (MAVS/IPS1) which activates CC the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon CC regulatory factors: IRF3 and IRF7 which in turn activate transcription CC of antiviral immunological genes, including interferons (IFNs); IFN- CC alpha and IFN-beta. Responsible for detecting the Picornaviridae family CC members such as encephalomyocarditis virus (EMCV), mengo CC encephalomyocarditis virus (ENMG), and theiler's murine CC encephalomyelitis virus (TMEV). Can also detect other viruses such as CC dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved CC in antiviral signaling in response to viruses containing a dsDNA CC genome, such as vaccinia virus. Plays an important role in amplifying CC innate immune signaling through recognition of RNA metabolites that are CC produced during virus infection by ribonuclease L (RNase L). May play CC an 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:12015121, ECO:0000269|PubMed:16625202, CC ECO:0000269|PubMed:17942531, ECO:0000269|PubMed:19656871, CC ECO:0000269|PubMed:21217758}. 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:0000250|UniProtKB:Q9BYX4}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000250|UniProtKB:Q9BYX4}; 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. Interacts with MAVS/IPS1. Interacts CC (via the CARD domains) with TKFC, the interaction is inhibited by viral CC infection. Interacts with PCBP2. Interacts with NLRC5. Interacts with CC PIAS2-beta. Interacts with DDX60. Interacts with ANKRD17. Interacts CC with IKBKE. Interacts with ATG5 and ATG12, either as ATG5 and ATG12 CC monomers or as ATG12-ATG5 conjugates. Interacts with ZCCHC3; leading to CC activate IFIH1/MDA5. Interacts with RNF123. Interacts with DDX3X. CC Interacts with NOD1; this interaction promotes transcription of CC antiviral genes and inhibition of viral replication. Interacts with CC ECSIT; this interaction bridges IFIH1 to the MAVS complex at the CC mitochondrion. {ECO:0000250|UniProtKB:Q9BYX4}. CC -!- INTERACTION: CC Q8R5F7-1; P11207: P/V; Xeno; NbExp=3; IntAct=EBI-16019291, EBI-6148694; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12015121}. Nucleus CC {ECO:0000250|UniProtKB:Q9BYX4}. Mitochondrion CC {ECO:0000250|UniProtKB:Q9BYX4}. Note=Upon viral RNA stimulation and CC ISGylation, translocates from cytosol to mitochondrion. May be found in CC the nucleus, during apoptosis. {ECO:0000250|UniProtKB:Q9BYX4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8R5F7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8R5F7-2; Sequence=VSP_013339; CC -!- TISSUE SPECIFICITY: Expression is prominent in lung, liver, kidney, CC heart and spleen (at protein level). Widely expressed at low level. CC {ECO:0000269|PubMed:12015121}. CC -!- INDUCTION: By interferon (IFN). 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:0000269|PubMed:12015121}. CC -!- PTM: Sumoylated. Sumoylation positively regulates its role in type I CC interferon induction and is enhanced by PIAS2-beta. CC {ECO:0000250|UniProtKB:Q9BYX4}. CC -!- PTM: Ubiquitinated by RNF125, leading to its degradation by the CC proteasome. USP17/UPS17L2-dependent deubiquitination positively CC regulates the receptor. Ubiquitinated by TRIM25 via 'Lys-63'-linked CC ubiquitination, promoting activation of IFIH1/MDA5. Ubiquitinated by CC TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal CC degradation. Ubiquitinated by TRIM65 via 'Lys-63'-linked CC ubiquitination, promoting activation of IFIH1/MDA5. CC {ECO:0000250|UniProtKB:Q9BYX4}. CC -!- PTM: ISGylated by ISG15. ISGylation increases upon infection with CC viruses. ISGylation at Lys-23 and Lys-43 is dependent of CC dephosphorylation, regulates mitochondrial translocation and CC oligomerization. Essential for IFIH1/MDA5-mediated cytokine responses CC and restriction of virus replication. {ECO:0000250|UniProtKB:Q9BYX4}. CC -!- PTM: Phosphorylated. Dephosphorylated by phsophatases PP1; CC dephosphorylation precedes and is required for ISGylation. CC {ECO:0000250|UniProtKB:Q9BYX4}. CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH25508.1; 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; AY075132; AAL77205.1; -; mRNA. DR EMBL; AF374384; AAM21359.1; -; mRNA. DR EMBL; AK018602; BAB31303.2; -; mRNA. DR EMBL; AK037057; BAC29687.2; -; mRNA. DR EMBL; AK040519; BAC30614.1; -; mRNA. DR EMBL; AK153018; BAE31652.1; -; mRNA. DR EMBL; AL929246; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC004031; AAH04031.1; -; mRNA. DR EMBL; BC019605; AAH19605.1; -; mRNA. DR EMBL; BC025508; AAH25508.1; ALT_INIT; mRNA. DR EMBL; BC080200; AAH80200.1; -; mRNA. DR CCDS; CCDS16068.1; -. [Q8R5F7-1] DR CCDS; CCDS50594.1; -. [Q8R5F7-2] DR RefSeq; NP_001157949.1; NM_001164477.1. [Q8R5F7-2] DR RefSeq; NP_082111.2; NM_027835.3. [Q8R5F7-1] DR PDB; 3TS9; X-ray; 2.00 A; A=545-697. DR PDB; 6G19; EM; 3.68 A; A=307-1020. DR PDB; 6G1S; EM; 3.93 A; A=310-1020. DR PDB; 6G1X; EM; 3.93 A; A=307-1020. DR PDB; 6GJZ; EM; 4.06 A; A=1-1025. DR PDB; 6GKH; EM; 4.06 A; A=1-1025. DR PDB; 6GKM; EM; 3.87 A; A=1-1025. DR PDB; 6H61; EM; 4.02 A; A=1-1025. DR PDB; 6H66; EM; 4.16 A; A=1-1025. DR PDB; 7BKP; EM; 2.80 A; A=1-1025. DR PDB; 7BKQ; EM; 3.40 A; A=307-1020. DR PDB; 7NGA; EM; 3.90 A; A=1-1025. DR PDB; 7NIC; EM; 4.30 A; A=1-1025. DR PDB; 7NIQ; EM; 4.30 A; B=1-1025. DR PDBsum; 3TS9; -. DR PDBsum; 6G19; -. DR PDBsum; 6G1S; -. DR PDBsum; 6G1X; -. DR PDBsum; 6GJZ; -. DR PDBsum; 6GKH; -. DR PDBsum; 6GKM; -. DR PDBsum; 6H61; -. DR PDBsum; 6H66; -. DR PDBsum; 7BKP; -. DR PDBsum; 7BKQ; -. DR PDBsum; 7NGA; -. DR PDBsum; 7NIC; -. DR PDBsum; 7NIQ; -. DR AlphaFoldDB; Q8R5F7; -. DR EMDB; EMD-0012; -. DR EMDB; EMD-0023; -. DR EMDB; EMD-0024; -. DR EMDB; EMD-0143; -. DR EMDB; EMD-0145; -. DR EMDB; EMD-11937; -. DR EMDB; EMD-12092; -. DR EMDB; EMD-12213; -. DR EMDB; EMD-12288; -. DR EMDB; EMD-12294; -. DR EMDB; EMD-4338; -. DR EMDB; EMD-4340; -. DR EMDB; EMD-4341; -. DR SMR; Q8R5F7; -. DR BioGRID; 214799; 4. DR DIP; DIP-60085N; -. DR IntAct; Q8R5F7; 1. DR STRING; 10090.ENSMUSP00000028259; -. DR iPTMnet; Q8R5F7; -. DR PhosphoSitePlus; Q8R5F7; -. DR SwissPalm; Q8R5F7; -. DR EPD; Q8R5F7; -. DR jPOST; Q8R5F7; -. DR MaxQB; Q8R5F7; -. DR PaxDb; 10090-ENSMUSP00000028259; -. DR PeptideAtlas; Q8R5F7; -. DR ProteomicsDB; 273099; -. [Q8R5F7-1] DR ProteomicsDB; 273100; -. [Q8R5F7-2] DR Antibodypedia; 805; 567 antibodies from 42 providers. DR DNASU; 71586; -. DR Ensembl; ENSMUST00000028259.12; ENSMUSP00000028259.6; ENSMUSG00000026896.15. [Q8R5F7-1] DR Ensembl; ENSMUST00000112459.4; ENSMUSP00000108078.4; ENSMUSG00000026896.15. [Q8R5F7-2] DR GeneID; 71586; -. DR KEGG; mmu:71586; -. DR UCSC; uc008jvm.2; mouse. [Q8R5F7-1] DR UCSC; uc012bvy.1; mouse. [Q8R5F7-2] DR AGR; MGI:1918836; -. DR CTD; 64135; -. DR MGI; MGI:1918836; Ifih1. DR VEuPathDB; HostDB:ENSMUSG00000026896; -. DR eggNOG; KOG0354; Eukaryota. DR GeneTree; ENSGT00940000153173; -. DR HOGENOM; CLU_006888_0_0_1; -. DR InParanoid; Q8R5F7; -. DR OMA; TFCQMNP; -. DR OrthoDB; 342391at2759; -. DR PhylomeDB; Q8R5F7; -. DR TreeFam; TF330258; -. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR BioGRID-ORCS; 71586; 1 hit in 79 CRISPR screens. DR PRO; PR:Q8R5F7; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q8R5F7; Protein. DR Bgee; ENSMUSG00000026896; Expressed in small intestine Peyer's patch and 189 other cell types or tissues. DR ExpressionAtlas; Q8R5F7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0032559; F:adenyl ribonucleotide binding; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB. DR GO; GO:0038187; F:pattern recognition receptor activity; ISO:MGI. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0035639; F:purine ribonucleoside triphosphate binding; ISO:MGI. DR GO; GO:0043021; F:ribonucleoprotein complex binding; ISO:MGI. DR GO; GO:0003723; F:RNA binding; ISO:MGI. DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB. DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0140374; P:antiviral innate immune response; IMP:MGI. DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISS:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB. DR GO; GO:0039530; P:MDA-5 signaling pathway; ISS:UniProtKB. DR GO; GO:0045071; P:negative regulation of viral genome replication; ISS:UniProtKB. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB. DR GO; GO:0060760; P:positive regulation of response to cytokine stimulus; ISS:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IDA:MGI. DR GO; GO:0016925; P:protein sumoylation; ISS:UniProtKB. DR GO; GO:0009615; P:response to virus; IMP:UniProtKB. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IMP:MGI. 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; SSF47986; DEATH domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS51789; RLR_CTR; 1. DR Genevisible; Q8R5F7; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Antiviral defense; ATP-binding; KW Cytoplasm; Helicase; Hydrolase; Immunity; Innate immunity; Isopeptide bond; KW Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; RNA-binding; Ubl conjugation; Zinc. FT CHAIN 1..1025 FT /note="Interferon-induced helicase C domain-containing FT protein 1" FT /id="PRO_0000102013" FT DOMAIN 7..97 FT /note="CARD 1" FT DOMAIN 110..190 FT /note="CARD 2" FT DOMAIN 317..510 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 700..872 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 273..297 FT /note="Disordered" 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 SITE 216..217 FT /note="Cleavage" FT SITE 251..252 FT /note="Cleavage" FT MOD_RES 289 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 291 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 302 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 645 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 648 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 828 FT /note="Phosphoserine; by RIOK3" FT /evidence="ECO:0000250|UniProtKB:Q9BYX4" FT CROSSLNK 23 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000250|UniProtKB:Q9BYX4" FT CROSSLNK 43 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000250|UniProtKB:Q9BYX4" FT VAR_SEQ 207..255 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013339" FT CONFLICT 100 FT /note="T -> I (in Ref. 6; AAH80200)" FT /evidence="ECO:0000305" FT CONFLICT 339 FT /note="V -> E (in Ref. 4; BAE31652)" FT /evidence="ECO:0000305" FT CONFLICT 412..414 FT /note="IST -> TRP (in Ref. 6; AAH25508)" FT /evidence="ECO:0000305" FT CONFLICT 624 FT /note="Y -> H (in Ref. 6; AAH25508)" FT /evidence="ECO:0000305" FT CONFLICT 629 FT /note="T -> A (in Ref. 3; AAM21359)" FT /evidence="ECO:0000305" FT CONFLICT 647 FT /note="K -> E (in Ref. 6; AAH25508/AAH04031/AAH80200)" FT /evidence="ECO:0000305" FT CONFLICT 889 FT /note="K -> E (in Ref. 4; BAB31303)" FT /evidence="ECO:0000305" FT HELIX 311..321 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 326..329 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 336..353 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 360..365 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 367..376 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 379..382 FT /evidence="ECO:0007829|PDB:7BKP" FT TURN 383..385 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 388..390 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 393..395 FT /evidence="ECO:0007829|PDB:7BKQ" FT HELIX 397..400 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 401..407 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 409..414 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 415..426 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 435..437 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 439..445 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 446..448 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 454..474 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 475..477 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 484..490 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 500..513 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 526..532 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 537..543 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 550..565 FT /evidence="ECO:0007829|PDB:3TS9" FT STRAND 574..576 FT /evidence="ECO:0007829|PDB:7BKQ" FT HELIX 577..593 FT /evidence="ECO:0007829|PDB:3TS9" FT HELIX 596..617 FT /evidence="ECO:0007829|PDB:3TS9" FT HELIX 620..640 FT /evidence="ECO:0007829|PDB:3TS9" FT HELIX 671..691 FT /evidence="ECO:0007829|PDB:3TS9" FT HELIX 694..696 FT /evidence="ECO:0007829|PDB:3TS9" FT HELIX 699..715 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 721..724 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 728..740 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 742..747 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 751..754 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 761..763 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 768..780 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 785..789 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 790..792 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 793..795 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 802..808 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 813..821 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 825..827 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 829..839 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 840..862 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 866..890 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 900..902 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 904..910 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 913..916 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 919..923 FT /evidence="ECO:0007829|PDB:7BKP" FT TURN 924..926 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 927..930 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 933..936 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 940..942 FT /evidence="ECO:0007829|PDB:7BKQ" FT HELIX 945..948 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 959..961 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 967..974 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 977..982 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 984..986 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 987..990 FT /evidence="ECO:0007829|PDB:7BKP" FT STRAND 992..994 FT /evidence="ECO:0007829|PDB:7BKP" FT HELIX 1003..1005 FT /evidence="ECO:0007829|PDB:7BKP" FT TURN 1015..1018 FT /evidence="ECO:0007829|PDB:7BKQ" SQ SEQUENCE 1025 AA; 115971 MW; 708FCAC690C9F6D8 CRC64; MSIVCSAEDS FRNLILFFRP RLKMYIQVEP VLDHLIFLSA ETKEQILKKI NTCGNTSAAE LLLSTLEQGQ WPLGWTQMFV EALEHSGNPL AARYVKPTLT DLPSPSSETA HDECLHLLTL LQPTLVDKLL INDVLDTCFE KGLLTVEDRN RISAAGNSGN ESGVRELLRR IVQKENWFST FLDVLRQTGN DALFQELTGG GCPEDNTDLA NSSHRDGPAA NECLLPAVDE SSLETEAWNV DDILPEASCT DSSVTTESDT SLAEGSVSCF DESLGHNSNM GRDSGTMGSD SDESVIQTKR VSPEPELQLR PYQMEVAQPA LDGKNIIICL PTGSGKTRVA VYITKDHLDK KKQASESGKV IVLVNKVMLA EQLFRKEFNP YLKKWYRIIG LSGDTQLKIS FPEVVKSYDV IISTAQILEN SLLNLESGDD DGVQLSDFSL IIIDECHHTN KEAVYNNIMR RYLKQKLRNN DLKKQNKPAI PLPQILGLTA SPGVGAAKKQ SEAEKHILNI CANLDAFTIK TVKENLGQLK HQIKEPCKKF VIADDTRENP FKEKLLEIMA SIQTYCQKSP MSDFGTQHYE QWAIQMEKKA AKDGNRKDRV CAEHLRKYNE ALQINDTIRM IDAYSHLETF YTDEKEKKFA VLNDSDKSDD EASSCNDQLK GDVKKSLKLD ETDEFLMNLF FDNKKMLKKL AENPKYENEK LIKLRNTILE QFTRSEESSR GIIFTKTRQS TYALSQWIME NAKFAEVGVK AHHLIGAGHS SEVKPMTQTE QKEVISKFRT GEINLLIATT VAEEGLDIKE CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVTSSGSGV TEREIVNDFR EKMMYKAINR VQNMKPEEYA HKILELQVQS ILEKKMKVKR SIAKQYNDNP SLITLLCKNC SMLVCSGENI HVIEKMHHVN MTPEFKGLYI VRENKALQKK FADYQTNGEI ICKCGQAWGT MMVHKGLDLP CLKIRNFVVN FKNNSPKKQY KKWVELPIRF PDLDYSEYCL YSDED //