LOCUS       NM_022168               3581 bp    mRNA    linear   PRI 05-DEC-2024
DEFINITION  Homo sapiens interferon induced with helicase C domain 1 (IFIH1),
            mRNA.
ACCESSION   NM_022168
VERSION     NM_022168.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3581)
  AUTHORS   Zhang,S., Huang,W., Wu,X., Chen,H., Wang,L., Chao,J., Xie,J. and
            Qiu,H.
  TITLE     IBR1, a novel endogenous IFIH1-binding dsRNA, governs IFIH1
            activation and M1 macrophage polarisation in ARDS
  JOURNAL   Clin Transl Med 14 (9), e70027 (2024)
   PUBMED   39313944
  REMARK    GeneRIF: IBR1, a novel endogenous IFIH1-binding dsRNA, governs
            IFIH1 activation and M1 macrophage polarisation in ARDS.
REFERENCE   2  (bases 1 to 3581)
  AUTHORS   Song,W., Bian,W.J., Li,H., Guo,Q.H., Wang,J., Tang,B., Zhang,J.Y.,
            Wei,W., Liu,X.R., Liao,W.P., Li,B. and He,N.
  TITLE     IFIH1 variants are associated with generalised epilepsy preceded by
            febrile seizures
  JOURNAL   J Med Genet 61 (9), 895-903 (2024)
   PUBMED   38964834
  REMARK    GeneRIF: IFIH1 variants are associated with generalised epilepsy
            preceded by febrile seizures.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3581)
  AUTHORS   Guney,M.H., Nagalekshmi,K., McCauley,S.M., Carbone,C., Aydemir,O.
            and Luban,J.
  TITLE     IFIH1 (MDA5) is required for innate immune detection of
            intron-containing RNA expressed from the HIV-1 provirus
  JOURNAL   Proc Natl Acad Sci U S A 121 (29), e2404349121 (2024)
   PUBMED   38985764
  REMARK    GeneRIF: IFIH1 (MDA5) is required for innate immune detection of
            intron-containing RNA expressed from the HIV-1 provirus.
REFERENCE   4  (bases 1 to 3581)
  AUTHORS   Chan,Y.J., Liu,N.T., Hsin,F., Lu,J.Y., Lin,J.Y. and Liu,H.M.
  TITLE     Temporal regulation of MDA5 inactivation by Caspase-3 dependent
            cleavage of 14-3-3eta
  JOURNAL   PLoS Pathog 20 (6), e1012287 (2024)
   PUBMED   38843304
  REMARK    GeneRIF: Temporal regulation of MDA5 inactivation by Caspase-3
            dependent cleavage of 14-3-3eta.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3581)
  AUTHORS   Rizk,S.K., Farag,A.G.A., El-Ghlban,S. and Eldin Metwally,I.S.
  TITLE     Identifying the association between polymorphisms in the GZMB and
            IFIH1 genes and psoriasis in Egyptians
  JOURNAL   J Immunoassay Immunochem 45 (3), 189-209 (2024)
   PUBMED   38733267
  REMARK    GeneRIF: Identifying the association between polymorphisms in the
            GZMB and IFIH1 genes and psoriasis in Egyptians.
REFERENCE   6  (bases 1 to 3581)
  AUTHORS   Cocude,C., Truong,M.J., Billaut-Mulot,O., Delsart,V., Darcissac,E.,
            Capron,A., Mouton,Y. and Bahr,G.M.
  TITLE     A novel cellular RNA helicase, RH116, differentially regulates cell
            growth, programmed cell death and human immunodeficiency virus type
            1 replication
  JOURNAL   J Gen Virol 84 (Pt 12), 3215-3225 (2003)
   PUBMED   14645903
REFERENCE   7  (bases 1 to 3581)
  AUTHORS   Kovacsovics,M., Martinon,F., Micheau,O., Bodmer,J.L., Hofmann,K.
            and Tschopp,J.
  TITLE     Overexpression of Helicard, a CARD-containing helicase cleaved
            during apoptosis, accelerates DNA degradation
  JOURNAL   Curr Biol 12 (10), 838-843 (2002)
   PUBMED   12015121
  REMARK    Erratum:[Curr Biol. 2002 Sep 17;12(18):1633.]
REFERENCE   8  (bases 1 to 3581)
  AUTHORS   Kang,D.C., Gopalkrishnan,R.V., Wu,Q., Jankowsky,E., Pyle,A.M. and
            Fisher,P.B.
  TITLE     mda-5: An interferon-inducible putative RNA helicase with
            double-stranded RNA-dependent ATPase activity and melanoma
            growth-suppressive properties
  JOURNAL   Proc Natl Acad Sci U S A 99 (2), 637-642 (2002)
   PUBMED   11805321
  REMARK    GeneRIF: mda-5: An interferon-inducible putative RNA helicase with
            double-stranded RNA-dependent ATPase activity and melanoma
            growth-suppressive properties
REFERENCE   9  (bases 1 to 3581)
  AUTHORS   Chaudhary,P.M., Eby,M.T., Jasmin,A., Kumar,A., Liu,L. and Hood,L.
  TITLE     Activation of the NF-kappaB pathway by caspase 8 and its homologs
  JOURNAL   Oncogene 19 (39), 4451-4460 (2000)
   PUBMED   11002417
REFERENCE   10 (bases 1 to 3581)
  AUTHORS   Crow,Y.J.
  TITLE     Aicardi-Goutieres Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301648
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC046208.1, AF095844.1,
            BC111750.1 and AC007750.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 5, 2018 this sequence version replaced NM_022168.3.
            
            Summary: IFIH1 encodes MDA5 which is an intracellular sensor of
            viral RNA that triggers the innate immune response. Sensing RNA
            length and secondary structure, MDA5 binds dsRNA oligonucleotides
            with a modified DExD/H-box helicase core and a C-terminal domain,
            thus leading to a proinflammatory response that includes
            interferons. It has been shown that Coronaviruses (CoVs) as well as
            various other virus families, are capable of evading the
            MDA5-dependent interferon response, thus impeding the activation of
            the innate immune response to infection. MDA5 has also been shown
            to play an important role in enhancing natural killer cell function
            in malaria infection. In addition to its protective role in
            antiviral responses, MDA5 has been implicated in autoimmune and
            autoinflammatory diseases such as type 1 diabetes, systemic lupus
            erythematosus, and Aicardi-Goutieres syndrome[provided by RefSeq,
            Jul 2020].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK314611.1, AF095844.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            coronavirus related    :: involved in immune response or antiviral
                                      activity
            MANE Ensembl match     :: ENST00000649979.2/ ENSP00000497271.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-830               BC046208.1         1-830
            831-2150            AF095844.1         622-1941
            2151-2904           BC111750.1         1842-2595
            2905-3574           AF095844.1         2696-3365
            3575-3581           AC007750.3         148929-148935       c
FEATURES             Location/Qualifiers
     source          1..3581
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q24.2"
     gene            1..3581
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /note="interferon induced with helicase C domain 1"
                     /db_xref="GeneID:64135"
                     /db_xref="HGNC:HGNC:18873"
                     /db_xref="MIM:606951"
     exon            1..830
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     CDS             378..3455
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /EC_number="3.6.4.13"
                     /note="helicard; DEAD/H (Asp-Glu-Ala-Asp/His) box
                     polypeptide; helicase with 2 CARD domains; RNA
                     helicase-DEAD box protein 116; murabutide down-regulated
                     protein; melanoma differentiation-associated protein 5;
                     CADM-140 autoantigen; clinically amyopathic
                     dermatomyositis autoantigen 140 kDa; RIG-I-like receptor
                     2; melanoma differentiation-associated gene 5"
                     /codon_start=1
                     /product="interferon-induced helicase C domain-containing
                     protein 1"
                     /protein_id="NP_071451.2"
                     /db_xref="CCDS:CCDS2217.1"
                     /db_xref="GeneID:64135"
                     /db_xref="HGNC:HGNC:18873"
                     /db_xref="MIM:606951"
                     /translation="MSNGYSTDENFRYLISCFRARVKMYIQVEPVLDYLTFLPAEVKE
                     QIQRTVATSGNMQAVELLLSTLEKGVWHLGWTREFVEALRRTGSPLAARYMNPELTDL
                     PSPSFENAHDEYLQLLNLLQPTLVDKLLVRDVLDKCMEEELLTIEDRNRIAAAENNGN
                     ESGVRELLKRIVQKENWFSAFLNVLRQTGNNELVQELTGSDCSESNAEIENLSQVDGP
                     QVEEQLLSTTVQPNLEKEVWGMENNSSESSFADSSVVSESDTSLAEGSVSCLDESLGH
                     NSNMGSDSGTMGSDSDEENVAARASPEPELQLRPYQMEVAQPALEGKNIIICLPTGSG
                     KTRVAVYIAKDHLDKKKKASEPGKVIVLVNKVLLVEQLFRKEFQPFLKKWYRVIGLSG
                     DTQLKISFPEVVKSCDIIISTAQILENSLLNLENGEDAGVQLSDFSLIIIDECHHTNK
                     EAVYNNIMRHYLMQKLKNNRLKKENKPVIPLPQILGLTASPGVGGATKQAKAEEHILK
                     LCANLDAFTIKTVKENLDQLKNQIQEPCKKFAIADATREDPFKEKLLEIMTRIQTYCQ
                     MSPMSDFGTQPYEQWAIQMEKKAAKEGNRKERVCAEHLRKYNEALQINDTIRMIDAYT
                     HLETFYNEEKDKKFAVIEDDSDEGGDDEYCDGDEDEDDLKKPLKLDETDRFLMTLFFE
                     NNKMLKRLAENPEYENEKLTKLRNTIMEQYTRTEESARGIIFTKTRQSAYALSQWITE
                     NEKFAEVGVKAHHLIGAGHSSEFKPMTQNEQKEVISKFRTGKINLLIATTVAEEGLDI
                     KECNIVIRYGLVTNEIAMVQARGRARADESTYVLVAHSGSGVIEHETVNDFREKMMYK
                     AIHCVQNMKPEEYAHKILELQMQSIMEKKMKTKRNIAKHYKNNPSLITFLCKNCSVLA
                     CSGEDIHVIEKMHHVNMTPEFKELYIVRENKALQKKCADYQINGEIICKCGQAWGTMM
                     VHKGLDLPCLKIRNFVVVFKNNSTKKQYKKWVELPITFPNLDYSECCLFSDED"
     exon            831..999
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1000..1146
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1147..1251
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1252..1472
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1473..1683
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1684..1901
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1902..2018
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2019..2142
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2143..2421
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2422..2681
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2682..2831
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2832..2993
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2994..3184
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3185..3275
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3276..3581
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3552..3557
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /note="hexamer: AATAAA"
     polyA_site      3576
                     /gene="IFIH1"
                     /gene_synonym="AGS7; Hlcd; IDDM19; IMD95; MDA-5; MDA5;
                     RLR-2; SGMRT1"
                     /note="major polyA site"
ORIGIN      
        1 caaactctgt aagaactgcc tgacagaaag ctggactcaa agctcctacc cgagtgtgca
       61 gcaggatcgc cccggtccgg gaccccaggc gcacaccgca gagtccaaag tgccgcgcct
      121 gccggccgca cctgcctgcc gcggccccgc gcgccgcccc gctgcccacc tgcccgcctg
      181 cccacctgcc caggtgcgag tgcagccccg cgcgccggcc tgagagccct gtggacaacc
      241 tcgtcattgt caggcacaga gcggtagacc ctgcttctct aagtgggcag cggacagcgg
      301 cacgcacatt tcacctgtcc cgcagacaac agcaccatct gcttgggaga accctctccc
      361 ttctctgaga aagaaagatg tcgaatgggt attccacaga cgagaatttc cgctatctca
      421 tctcgtgctt cagggccagg gtgaaaatgt acatccaggt ggagcctgtg ctggactacc
      481 tgacctttct gcctgcagag gtgaaggagc agattcagag gacagtcgcc acctccggga
      541 acatgcaggc agttgaactg ctgctgagca ccttggagaa gggagtctgg caccttggtt
      601 ggactcggga attcgtggag gccctccgga gaaccggcag ccctctggcc gcccgctaca
      661 tgaaccctga gctcacggac ttgccctctc catcgtttga gaacgctcat gatgaatatc
      721 tccaactgct gaacctcctt cagcccactc tggtggacaa gcttctagtt agagacgtct
      781 tggataagtg catggaggag gaactgttga caattgaaga cagaaaccgg attgctgctg
      841 cagaaaacaa tggaaatgaa tcaggtgtaa gagagctact aaaaaggatt gtgcagaaag
      901 aaaactggtt ctctgcattt ctgaatgttc ttcgtcaaac aggaaacaat gaacttgtcc
      961 aagagttaac aggctctgat tgctcagaaa gcaatgcaga gattgagaat ttatcacaag
     1021 ttgatggtcc tcaagtggaa gagcaacttc tttcaaccac agttcagcca aatctggaga
     1081 aggaggtctg gggcatggag aataactcat cagaatcatc ttttgcagat tcttctgtag
     1141 tttcagaatc agacacaagt ttggcagaag gaagtgtcag ctgcttagat gaaagtcttg
     1201 gacataacag caacatgggc agtgattcag gcaccatggg aagtgattca gatgaagaga
     1261 atgtggcagc aagagcatcc ccggagccag aactccagct caggccttac caaatggaag
     1321 ttgcccagcc agccttggaa gggaagaata tcatcatctg cctccctaca gggagtggaa
     1381 aaaccagagt ggctgtttac attgccaagg atcacttaga caagaagaaa aaagcatctg
     1441 agcctggaaa agttatagtt cttgtcaata aggtactgct agttgaacag ctcttccgca
     1501 aggagttcca accatttttg aagaaatggt atcgtgttat tggattaagt ggtgataccc
     1561 aactgaaaat atcatttcca gaagttgtca agtcctgtga tattattatc agtacagctc
     1621 aaatccttga aaactccctc ttaaacttgg aaaatggaga agatgctggt gttcaattgt
     1681 cagacttttc cctcattatc attgatgaat gtcatcacac caacaaagaa gcagtgtata
     1741 ataacatcat gaggcattat ttgatgcaga agttgaaaaa caatagactc aagaaagaaa
     1801 acaaaccagt gattcccctt cctcagatac tgggactaac agcttcacct ggtgttggag
     1861 gggccacgaa gcaagccaaa gctgaagaac acattttaaa actatgtgcc aatcttgatg
     1921 catttactat taaaactgtt aaagaaaacc ttgatcaact gaaaaaccaa atacaggagc
     1981 catgcaagaa gtttgccatt gcagatgcaa ccagagaaga tccatttaaa gagaaacttc
     2041 tagaaataat gacaaggatt caaacttatt gtcaaatgag tccaatgtca gattttggaa
     2101 ctcaacccta tgaacaatgg gccattcaaa tggaaaaaaa agctgcaaaa gaaggaaatc
     2161 gcaaagaacg tgtttgtgca gaacatttga ggaagtacaa tgaggcccta caaattaatg
     2221 acacaattcg aatgatagat gcgtatactc atcttgaaac tttctataat gaagagaaag
     2281 ataagaagtt tgcagtcata gaagatgata gtgatgaggg tggtgatgat gagtattgtg
     2341 atggtgatga agatgaggat gatttaaaga aacctttgaa actggatgaa acagatagat
     2401 ttctcatgac tttatttttt gaaaacaata aaatgttgaa aaggctggct gaaaacccag
     2461 aatatgaaaa tgaaaagctg accaaattaa gaaataccat aatggagcaa tatactagga
     2521 ctgaggaatc agcacgagga ataatcttta caaaaacacg acagagtgca tatgcgcttt
     2581 cccagtggat tactgaaaat gaaaaatttg ctgaagtagg agtcaaagcc caccatctga
     2641 ttggagctgg acacagcagt gagttcaaac ccatgacaca gaatgaacaa aaagaagtca
     2701 ttagtaaatt tcgcactgga aaaataaatc tgcttatcgc taccacagtg gcagaagaag
     2761 gtctggatat taaagaatgt aacattgtta tccgttatgg tctcgtcacc aatgaaatag
     2821 ccatggtcca ggcccgtggt cgagccagag ctgatgagag cacctacgtc ctggttgctc
     2881 acagtggttc aggagttatc gaacatgaga cagttaatga tttccgagag aagatgatgt
     2941 ataaagctat acattgtgtt caaaatatga aaccagagga gtatgctcat aagattttgg
     3001 aattacagat gcaaagtata atggaaaaga aaatgaaaac caagagaaat attgccaagc
     3061 attacaagaa taacccatca ctaataactt tcctttgcaa aaactgcagt gtgctagcct
     3121 gttctgggga agatatccat gtaattgaga aaatgcatca cgtcaatatg accccagaat
     3181 tcaaggaact ttacattgta agagaaaaca aagcactgca aaagaagtgt gccgactatc
     3241 aaataaatgg tgaaatcatc tgcaaatgtg gccaggcttg gggaacaatg atggtgcaca
     3301 aaggcttaga tttgccttgt ctcaaaataa ggaattttgt agtggttttc aaaaataatt
     3361 caacaaagaa acaatacaaa aagtgggtag aattacctat cacatttccc aatcttgact
     3421 attcagaatg ctgtttattt agtgatgagg attagcactt gattgaagat tcttttaaaa
     3481 tactatcagt taaacattta atatgattat gattaatgta ttcattatgc tacagaactg
     3541 acataagaat caataaaatg attgttttac tctgcattga a
//
