Protein: Interferon-induced helicase C domain-containing protein 1 (EC 3.6.4.13) (Helicase with 2 CARD domains) (Helicard) (Interferon induced with helicase C domain protein 1) (Melanoma differentiation-associated protein 5) (MDA-5) (RIG-I-like receptor 2) (RLR-2) (Q8R5F7)
Organism: Mus musculus (Mouse)
Function: Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and theiler's murine encephalomyelitis virus (TMEV). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:12015121}. Nucleus {ECO:0000250|UniProtKB:Q9BYX4}. Mitochondrion {ECO:0000250|UniProtKB:Q9BYX4}. Note=Upon viral RNA stimulation and ISGylation, translocates from cytosol to mitochondrion. May be found in the nucleus, during apoptosis. {ECO:0000250|UniProtKB:Q9BYX4}.
Interaction partners:
- Mitochondrial antiviral-signaling protein
- ATP-dependent RNA helicase DHX58
- Protein NLRC5
- Antiviral innate immune response effector IFIT1
- E3 ubiquitin/ISG15 ligase TRIM25
- E3 ubiquitin-protein ligase RNF125
- Toll-like receptor 3
- Ubiquitin-like protein ISG15
- Ubiquitin-like protein ATG12
- Interferon-induced, double-stranded RNA-activated protein kinase
Sequence:
MSIVCSAEDSFRNLILFFRPRLKMYIQVEPVLDHLIFLSAETKEQILKKINTCGNTSAAELLLSTLEQGQWPLGWTQMFVEALEHSGNPLAARYVKPTLTDLPSPSSETAHDECLHLLTLLQPTLVDKLLINDVLDTCFEKGLLTVEDRNRISAAGNSGNESGVRELLRRIVQKENWFSTFLDVLRQTGNDALFQELTGGGCPEDNTDLANSSHRDGPAANECLLPAVDESSLETEAWNVDDILPEASCTDSSVTTESDTSLAEGSVSCFDESLGHNSNMGRDSGTMGSDSDESVIQTKRVSPEPELQLRPYQMEVAQPALDGKNIIICLPTGSGKTRVAVYITKDHLDKKKQASESGKVIVLVNKVMLAEQLFRKEFNPYLKKWYRIIGLSGDTQLKISFPEVVKSYDVIISTAQILENSLLNLESGDDDGVQLSDFSLIIIDECHHTNKEAVYNNIMRRYLKQKLRNNDLKKQNKPAIPLPQILGLTASPGVGAAKKQSEAEKHILNICANLDAFTIKTVKENLGQLKHQIKEPCKKFVIADDTRENPFKEKLLEIMASIQTYCQKSPMSDFGTQHYEQWAIQMEKKAAKDGNRKDRVCAEHLRKYNEALQINDTIRMIDAYSHLETFYTDEKEKKFAVLNDSDKSDDEASSCNDQLKGDVKKSLKLDETDEFLMNLFFDNKKMLKKLAENPKYENEKLIKLRNTILEQFTRSEESSRGIIFTKTRQSTYALSQWIMENAKFAEVGVKAHHLIGAGHSSEVKPMTQTEQKEVISKFRTGEINLLIATTVAEEGLDIKECNIVIRYGLVTNEIAMVQARGRARADESTYVLVTSSGSGVTEREIVNDFREKMMYKAINRVQNMKPEEYAHKILELQVQSILEKKMKVKRSIAKQYNDNPSLITLLCKNCSMLVCSGENIHVIEKMHHVNMTPEFKGLYIVRENKALQKKFADYQTNGEIICKCGQAWGTMMVHKGLDLPCLKIRNFVVNFKNNSPKKQYKKWVELPIRFPDLDYSEYCLYSDED