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, Spleen,
RC 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};
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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 Genevisible; Q8R5F7; MM.
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.
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
//
