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Q9BYX4

- IFIH1_HUMAN

UniProt

Q9BYX4 - IFIH1_HUMAN

Protein

Interferon-induced helicase C domain-containing protein 1

Gene

IFIH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 3 (20 Mar 2007)
      Previous versions | rss
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    Functioni

    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 proinflammatory 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) and mengo encephalomyocarditis virus (ENMG). 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.5 Publications

    Catalytic activityi

    ATP + H2O = ADP + phosphate.

    Cofactori

    Zinc.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei208 – 2092CleavageBy similarity
    Sitei216 – 2172CleavageBy similarity
    Sitei251 – 2522CleavageBy similarity
    Metal bindingi907 – 9071Zinc
    Metal bindingi910 – 9101Zinc
    Metal bindingi962 – 9621Zinc
    Metal bindingi964 – 9641Zinc

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. DNA binding Source: InterPro
    3. double-stranded RNA binding Source: UniProtKB
    4. helicase activity Source: UniProtKB-KW
    5. protein binding Source: UniProtKB
    6. ribonucleoprotein complex binding Source: UniProtKB
    7. single-stranded RNA binding Source: UniProtKB
    8. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. cytoplasmic pattern recognition receptor signaling pathway in response to virus Source: UniProtKB
    2. detection of virus Source: BHF-UCL
    3. innate immune response Source: UniProtKB
    4. negative regulation of type I interferon production Source: Reactome
    5. positive regulation of interferon-alpha production Source: UniProtKB
    6. positive regulation of interferon-beta production Source: UniProtKB
    7. protein sumoylation Source: UniProtKB
    8. regulation of apoptotic process Source: InterPro
    9. regulation of type III interferon production Source: UniProtKB
    10. response to virus Source: UniProtKB
    11. viral process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Helicase, Hydrolase

    Keywords - Biological processi

    Antiviral defense, Host-virus interaction, Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_198532. Negative regulators of RIG-I/MDA5 signaling.
    REACT_24938. TRAF6 mediated IRF7 activation.
    REACT_24969. TRAF6 mediated NF-kB activation.
    REACT_25026. TRAF3-dependent IRF activation pathway.
    REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
    REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon-induced helicase C domain-containing protein 1 (EC:3.6.4.13)
    Alternative name(s):
    Clinically amyopathic dermatomyositis autoantigen 140 kDa
    Short name:
    CADM-140 autoantigen
    Helicase with 2 CARD domains
    Short name:
    Helicard
    Interferon-induced with helicase C domain protein 1
    Melanoma differentiation-associated protein 5
    Short name:
    MDA-5
    Murabutide down-regulated protein
    RIG-I-like receptor 2
    Short name:
    RLR-2
    RNA helicase-DEAD box protein 116
    Gene namesi
    Name:IFIH1
    Synonyms:MDA5, RH116
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:18873. IFIH1.

    Subcellular locationi

    Cytoplasm 2 Publications. Nucleus Curated
    Note: May be found in the nucleus, during apoptosis.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Diabetes mellitus, insulin-dependent, 19 (IDDM19) [MIM:610155]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
    Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti946 – 9461A → T Associated with susceptibility to IDDM19. 3 Publications
    Corresponds to variant rs1990760 [ dbSNP | Ensembl ].
    VAR_021595
    IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD).

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi251 – 2511D → A: No cleavage and no acceleration of DNA degradation. 1 Publication
    Mutagenesisi444 – 4441E → A: No acceleration of DNA degradation, no binding to ATP, and no helicase activity. 1 Publication

    Keywords - Diseasei

    Diabetes mellitus

    Organism-specific databases

    MIMi610155. phenotype.
    PharmGKBiPA134889215.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10251025Interferon-induced helicase C domain-containing protein 1PRO_0000102012Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei645 – 6451PhosphoserineBy similarity

    Post-translational modificationi

    During apoptosis, processed into 3 cleavage products. The helicase-containing fragment, once liberated from the CARD domains, translocate from the cytoplasm to the nucleus. The processed protein significantly sensitizes cells to DNA degradation By similarity.By similarity
    Sumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta.1 Publication
    Ubiquitinated. USP17/UPS17L2-dependent deubiquitination positively regulates the receptor.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9BYX4.
    PaxDbiQ9BYX4.
    PRIDEiQ9BYX4.

    PTM databases

    PhosphoSiteiQ9BYX4.

    Expressioni

    Tissue specificityi

    Widely expressed, at a low level. Expression is detected at slightly highest levels in placenta, pancreas and spleen and at barely levels in detectable brain, testis and lung.3 Publications

    Inductioni

    By interferon (IFN) and TNF.1 Publication

    Gene expression databases

    ArrayExpressiQ9BYX4.
    BgeeiQ9BYX4.
    CleanExiHS_IFIH1.
    GenevestigatoriQ9BYX4.

    Organism-specific databases

    HPAiHPA002656.

    Interactioni

    Subunit structurei

    Monomer in the absence of ligands and homodimerizes in the presence of dsRNA ligands. Can assemble into helical or linear polymeric filaments on long dsRNA. Interacts with MAVS/IPS1. Interacts with V protein of Simian virus 5, Human parainfluenza virus 2, Mumps virus, Sendai virus and Hendra virus. Binding to paramyxoviruses V proteins prevents IFN-beta induction, and the further establishment of an antiviral state. Interacts with PCBP2. Interacts with NLRC5. Interacts with PIAS2-beta. Interacts with DDX60.10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MAVSQ7Z4345EBI-6115771,EBI-995373
    P/VP112072EBI-6115771,EBI-6148694From a different organism.
    P/VP309272EBI-6115771,EBI-6599165From a different organism.
    P/VQ9EMA92EBI-6115771,EBI-6598728From a different organism.
    US11P044874EBI-6115771,EBI-6150681From a different organism.

    Protein-protein interaction databases

    BioGridi122082. 11 interactions.
    DIPiDIP-42607N.
    IntActiQ9BYX4. 15 interactions.
    MINTiMINT-3381993.
    STRINGi9606.ENSP00000263642.

    Structurei

    Secondary structure

    1
    1025
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi293 – 2997
    Helixi310 – 32011
    Beta strandi325 – 3284
    Helixi332 – 35221
    Beta strandi359 – 3657
    Helixi366 – 37510
    Helixi377 – 3815
    Turni382 – 3843
    Beta strandi387 – 3893
    Helixi400 – 4067
    Beta strandi408 – 4136
    Helixi414 – 4229
    Helixi434 – 4363
    Beta strandi438 – 4425
    Helixi454 – 47320
    Beta strandi483 – 4886
    Helixi900 – 9023
    Beta strandi903 – 9075
    Turni908 – 9103
    Beta strandi913 – 9164
    Helixi917 – 9193
    Beta strandi921 – 9233
    Turni924 – 9263
    Beta strandi927 – 9293
    Helixi934 – 9374
    Beta strandi938 – 9425
    Turni945 – 9473
    Beta strandi955 – 9628
    Beta strandi967 – 9748
    Beta strandi977 – 9826
    Helixi984 – 9863
    Beta strandi987 – 9915
    Turni992 – 9954
    Beta strandi996 – 9983
    Helixi1003 – 10053
    Helixi1015 – 10173

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2RQBNMR-A896-1025[»]
    3B6EX-ray1.60A277-490[»]
    3GA3X-ray1.45A893-1017[»]
    4GL2X-ray3.56A/B306-1017[»]
    ProteinModelPortaliQ9BYX4.
    SMRiQ9BYX4. Positions 4-199, 292-1025.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9BYX4.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini7 – 9791CARD 1Add
    BLAST
    Domaini110 – 19081CARD 2Add
    BLAST
    Domaini316 – 509194Helicase ATP-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini700 – 882183Helicase C-terminalPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the helicase family. RLR subfamily.Curated
    Contains 2 CARD domains.Curated
    Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
    Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG1111.
    HOGENOMiHOG000230992.
    HOVERGENiHBG106019.
    InParanoidiQ9BYX4.
    KOiK12647.
    OMAiKCGQAWG.
    OrthoDBiEOG7RV9FC.
    PhylomeDBiQ9BYX4.
    TreeFamiTF330258.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    3.40.50.300. 2 hits.
    InterProiIPR001315. CARD.
    IPR011029. DEATH-like_dom.
    IPR006935. Helicase/UvrB_dom.
    IPR014001. Helicase_ATP-bd.
    IPR001650. Helicase_C.
    IPR027417. P-loop_NTPase.
    IPR021673. RIG-I_C-RD.
    [Graphical view]
    PfamiPF00619. CARD. 1 hit.
    PF00271. Helicase_C. 1 hit.
    PF04851. ResIII. 1 hit.
    PF11648. RIG-I_C-RD. 1 hit.
    [Graphical view]
    SMARTiSM00487. DEXDc. 1 hit.
    SM00490. HELICc. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 6 hits.
    PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
    PS51194. HELICASE_CTER. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9BYX4-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSNGYSTDEN FRYLISCFRA RVKMYIQVEP VLDYLTFLPA EVKEQIQRTV     50
    ATSGNMQAVE LLLSTLEKGV WHLGWTREFV EALRRTGSPL AARYMNPELT 100
    DLPSPSFENA HDEYLQLLNL LQPTLVDKLL VRDVLDKCME EELLTIEDRN 150
    RIAAAENNGN ESGVRELLKR IVQKENWFSA FLNVLRQTGN NELVQELTGS 200
    DCSESNAEIE NLSQVDGPQV EEQLLSTTVQ PNLEKEVWGM ENNSSESSFA 250
    DSSVVSESDT SLAEGSVSCL DESLGHNSNM GSDSGTMGSD SDEENVAARA 300
    SPEPELQLRP YQMEVAQPAL EGKNIIICLP TGSGKTRVAV YIAKDHLDKK 350
    KKASEPGKVI VLVNKVLLVE QLFRKEFQPF LKKWYRVIGL SGDTQLKISF 400
    PEVVKSCDII ISTAQILENS LLNLENGEDA GVQLSDFSLI IIDECHHTNK 450
    EAVYNNIMRH YLMQKLKNNR LKKENKPVIP LPQILGLTAS PGVGGATKQA 500
    KAEEHILKLC ANLDAFTIKT VKENLDQLKN QIQEPCKKFA IADATREDPF 550
    KEKLLEIMTR IQTYCQMSPM SDFGTQPYEQ WAIQMEKKAA KEGNRKERVC 600
    AEHLRKYNEA LQINDTIRMI DAYTHLETFY NEEKDKKFAV IEDDSDEGGD 650
    DEYCDGDEDE DDLKKPLKLD ETDRFLMTLF FENNKMLKRL AENPEYENEK 700
    LTKLRNTIME QYTRTEESAR GIIFTKTRQS AYALSQWITE NEKFAEVGVK 750
    AHHLIGAGHS SEFKPMTQNE QKEVISKFRT GKINLLIATT VAEEGLDIKE 800
    CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVAHSGSGV IEHETVNDFR 850
    EKMMYKAIHC VQNMKPEEYA HKILELQMQS IMEKKMKTKR NIAKHYKNNP 900
    SLITFLCKNC SVLACSGEDI HVIEKMHHVN MTPEFKELYI VRENKALQKK 950
    CADYQINGEI ICKCGQAWGT MMVHKGLDLP CLKIRNFVVV FKNNSTKKQY 1000
    KKWVELPITF PNLDYSECCL FSDED 1025
    Length:1,025
    Mass (Da):116,689
    Last modified:March 20, 2007 - v3
    Checksum:i789CFB4824B92DC9
    GO
    Isoform 2 (identifier: Q9BYX4-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         208-221: EIENLSQVDGPQVE → GICNFTEEDSSNSA
         222-1025: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:221
    Mass (Da):25,129
    Checksum:i3C7139ECAC564BB5
    GO

    Sequence cautioni

    The sequence AAH78180.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.
    The sequence BAB71141.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti439 – 4391L → F in AAG54076. (PubMed:14645903)Curated
    Sequence conflicti475 – 4751N → H in BAB71141. (PubMed:14702039)Curated
    Sequence conflicti592 – 5921E → K in AAG34368. (PubMed:11805321)Curated
    Sequence conflicti598 – 5981R → S in AAG54076. (PubMed:14645903)Curated
    Sequence conflicti609 – 6091E → K in AAG54076. (PubMed:14645903)Curated
    Sequence conflicti782 – 7821K → R in BAB71141. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti460 – 4601H → R.
    Corresponds to variant rs10930046 [ dbSNP | Ensembl ].
    VAR_031226
    Natural varianti843 – 8431H → R.3 Publications
    Corresponds to variant rs3747517 [ dbSNP | Ensembl ].
    VAR_021594
    Natural varianti946 – 9461A → T Associated with susceptibility to IDDM19. 3 Publications
    Corresponds to variant rs1990760 [ dbSNP | Ensembl ].
    VAR_021595

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei208 – 22114EIENL…GPQVE → GICNFTEEDSSNSA in isoform 2. 1 PublicationVSP_013337Add
    BLAST
    Alternative sequencei222 – 1025804Missing in isoform 2. 1 PublicationVSP_013338Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF095844 mRNA. Translation: AAG34368.1.
    AY017378 mRNA. Translation: AAG54076.1.
    BC046208 mRNA. Translation: AAH46208.1.
    BC078180 mRNA. Translation: AAH78180.1. Sequence problems.
    BC111750 mRNA. Translation: AAI11751.1.
    AK056293 mRNA. Translation: BAB71141.1. Different initiation.
    CCDSiCCDS2217.1. [Q9BYX4-1]
    RefSeqiNP_071451.2. NM_022168.3. [Q9BYX4-1]
    UniGeneiHs.163173.

    Genome annotation databases

    EnsembliENST00000263642; ENSP00000263642; ENSG00000115267. [Q9BYX4-1]
    ENST00000421365; ENSP00000408450; ENSG00000115267. [Q9BYX4-2]
    GeneIDi64135.
    KEGGihsa:64135.
    UCSCiuc002uce.4. human. [Q9BYX4-1]
    uc002ucf.4. human. [Q9BYX4-2]

    Polymorphism databases

    DMDMi134047802.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF095844 mRNA. Translation: AAG34368.1 .
    AY017378 mRNA. Translation: AAG54076.1 .
    BC046208 mRNA. Translation: AAH46208.1 .
    BC078180 mRNA. Translation: AAH78180.1 . Sequence problems.
    BC111750 mRNA. Translation: AAI11751.1 .
    AK056293 mRNA. Translation: BAB71141.1 . Different initiation.
    CCDSi CCDS2217.1. [Q9BYX4-1 ]
    RefSeqi NP_071451.2. NM_022168.3. [Q9BYX4-1 ]
    UniGenei Hs.163173.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2RQB NMR - A 896-1025 [» ]
    3B6E X-ray 1.60 A 277-490 [» ]
    3GA3 X-ray 1.45 A 893-1017 [» ]
    4GL2 X-ray 3.56 A/B 306-1017 [» ]
    ProteinModelPortali Q9BYX4.
    SMRi Q9BYX4. Positions 4-199, 292-1025.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 122082. 11 interactions.
    DIPi DIP-42607N.
    IntActi Q9BYX4. 15 interactions.
    MINTi MINT-3381993.
    STRINGi 9606.ENSP00000263642.

    PTM databases

    PhosphoSitei Q9BYX4.

    Polymorphism databases

    DMDMi 134047802.

    Proteomic databases

    MaxQBi Q9BYX4.
    PaxDbi Q9BYX4.
    PRIDEi Q9BYX4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000263642 ; ENSP00000263642 ; ENSG00000115267 . [Q9BYX4-1 ]
    ENST00000421365 ; ENSP00000408450 ; ENSG00000115267 . [Q9BYX4-2 ]
    GeneIDi 64135.
    KEGGi hsa:64135.
    UCSCi uc002uce.4. human. [Q9BYX4-1 ]
    uc002ucf.4. human. [Q9BYX4-2 ]

    Organism-specific databases

    CTDi 64135.
    GeneCardsi GC02M163123.
    HGNCi HGNC:18873. IFIH1.
    HPAi HPA002656.
    MIMi 606951. gene.
    610155. phenotype.
    neXtProti NX_Q9BYX4.
    PharmGKBi PA134889215.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1111.
    HOGENOMi HOG000230992.
    HOVERGENi HBG106019.
    InParanoidi Q9BYX4.
    KOi K12647.
    OMAi KCGQAWG.
    OrthoDBi EOG7RV9FC.
    PhylomeDBi Q9BYX4.
    TreeFami TF330258.

    Enzyme and pathway databases

    Reactomei REACT_198532. Negative regulators of RIG-I/MDA5 signaling.
    REACT_24938. TRAF6 mediated IRF7 activation.
    REACT_24969. TRAF6 mediated NF-kB activation.
    REACT_25026. TRAF3-dependent IRF activation pathway.
    REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
    REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

    Miscellaneous databases

    ChiTaRSi IFIH1. human.
    EvolutionaryTracei Q9BYX4.
    GeneWikii MDA5.
    GenomeRNAii 64135.
    NextBioi 66034.
    PROi Q9BYX4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9BYX4.
    Bgeei Q9BYX4.
    CleanExi HS_IFIH1.
    Genevestigatori Q9BYX4.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    3.40.50.300. 2 hits.
    InterProi IPR001315. CARD.
    IPR011029. DEATH-like_dom.
    IPR006935. Helicase/UvrB_dom.
    IPR014001. Helicase_ATP-bd.
    IPR001650. Helicase_C.
    IPR027417. P-loop_NTPase.
    IPR021673. RIG-I_C-RD.
    [Graphical view ]
    Pfami PF00619. CARD. 1 hit.
    PF00271. Helicase_C. 1 hit.
    PF04851. ResIII. 1 hit.
    PF11648. RIG-I_C-RD. 1 hit.
    [Graphical view ]
    SMARTi SM00487. DEXDc. 1 hit.
    SM00490. HELICc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 6 hits.
    PROSITEi PS51192. HELICASE_ATP_BIND_1. 1 hit.
    PS51194. HELICASE_CTER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties."
      Kang D.-C., Gopalkrishnan R.V., Wu Q., Jankowsky E., Pyle A.M., Fisher P.B.
      Proc. Natl. Acad. Sci. U.S.A. 99:637-642(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Melanoma.
    2. "A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication."
      Cocude C., Truong M.-J., Billaut-Mulot O., Delsart V., Darcissac E., Capron A., Mouton Y., Bahr G.M.
      J. Gen. Virol. 84:3215-3225(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ARG-843.
      Tissue: Spleen.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS ARG-843 AND THR-946.
      Tissue: Uterus.
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 475-1025 (ISOFORM 1), VARIANTS ARG-843 AND THR-946.
    5. "Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation."
      Kovacsovics M., Martinon F., Micheau O., Bodmer J.-L., Hofmann K., Tschopp J.
      Curr. Biol. 12:838-843(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASP-251 AND GLU-444, TISSUE SPECIFICITY.
    6. Erratum
      Kovacsovics M., Martinon F., Micheau O., Bodmer J.-L., Hofmann K., Tschopp J.
      Curr. Biol. 12:1633-1633(2002)
    7. "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter."
      Andrejeva J., Childs K.S., Young D.F., Carlos T.S., Stock N., Goodbourn S., Randall R.E.
      Proc. Natl. Acad. Sci. U.S.A. 101:17264-17269(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PARAMYXOVIRUSES V PROTEIN.
    8. "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction."
      Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S.
      Nat. Immunol. 6:981-988(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAVS/IPS1.
    9. "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus."
      Meylan E., Curran J., Hofmann K., Moradpour D., Binder M., Bartenschlager R., Tschopp J.
      Nature 437:1167-1172(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAVS/IPS1.
    10. "RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease."
      Sato S., Hoshino K., Satoh T., Fujita T., Kawakami Y., Fujita T., Kuwana M.
      Arthritis Rheum. 60:2193-2200(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN CLINICALLY AMYOPATHIC DERMATOMYOSITIS, IDENTIFICATION AS CADM-140 AUTOANTIGEN.
    11. "Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2."
      Bamming D., Horvath C.M.
      J. Biol. Chem. 284:9700-9712(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Activation of MDA5 requires higher-order RNA structures generated during virus infection."
      Pichlmair A., Schulz O., Tan C.P., Rehwinkel J., Kato H., Takeuchi O., Akira S., Way M., Schiavo G., Reis e Sousa C.
      J. Virol. 83:10761-10769(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4."
      You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.
      Nat. Immunol. 10:1300-1308(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PCBP2.
    14. "NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways."
      Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., Zheng S., Chen Z.J., Wang R.F.
      Cell 141:483-496(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NLRC5.
    15. "The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling."
      Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B.
      Cell Res. 20:802-811(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP17L2.
    16. "The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody."
      Nakashima R., Imura Y., Kobayashi S., Yukawa N., Yoshifuji H., Nojima T., Kawabata D., Ohmura K., Usui T., Fujii T., Okawa K., Mimori T.
      Rheumatology 49:433-440(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN CLINICALLY AMYOPATHIC DERMATOMYOSITIS, IDENTIFICATION AS CADM-140 AUTOANTIGEN, IDENTIFICATION BY MASS SPECTROMETRY.
    17. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. "Immune signaling by RIG-I-like receptors."
      Loo Y.M., Gale M. Jr.
      Immunity 34:680-692(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    20. "RIG-I-like receptors: cytoplasmic sensors for non-self RNA."
      Kato H., Takahasi K., Fujita T.
      Immunol. Rev. 243:91-98(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    21. "Innate immune responses in human monocyte-derived dendritic cells are highly dependent on the size and the 5' phosphorylation of RNA molecules."
      Jiang M., Osterlund P., Sarin L.P., Poranen M.M., Bamford D.H., Guo D., Julkunen I.
      J. Immunol. 187:1713-1721(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    22. Cited for: REVIEW ON FUNCTION.
    23. "DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling."
      Miyashita M., Oshiumi H., Matsumoto M., Seya T.
      Mol. Cell. Biol. 31:3802-3819(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DDX60.
    24. "MDA5 is SUMOylated by PIAS2? in the upregulation of type I interferon signaling."
      Fu J., Xiong Y., Xu Y., Cheng G., Tang H.
      Mol. Immunol. 48:415-422(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION, INTERACTION WITH PIAS2-BETA.
    25. "2 methylate or not 2 methylate: viral evasion of the type I interferon response."
      Garcia-Sastre A.
      Nat. Immunol. 12:114-115(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    26. "Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5."
      Zuest R., Cervantes-Barragan L., Habjan M., Maier R., Neuman B.W., Ziebuhr J., Szretter K.J., Baker S.C., Barchet W., Diamond M.S., Siddell S.G., Ludewig B., Thiel V.
      Nat. Immunol. 12:137-143(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    27. "Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition."
      Peisley A., Lin C., Wu B., Orme-Johnson M., Liu M., Walz T., Hur S.
      Proc. Natl. Acad. Sci. U.S.A. 108:21010-21015(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    28. "A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region."
      Smyth D.J., Cooper J.D., Bailey R., Field S., Burren O., Smink L.J., Guja C., Ionescu-Tirgoviste C., Widmer B., Dunger D.B., Savage D.A., Walker N.M., Clayton D.G., Todd J.A.
      Nat. Genet. 38:617-619(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT THR-946, ASSOCIATION WITH IDDM19.
    29. "Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5."
      Li X., Lu C., Stewart M., Xu H., Strong R.K., Igumenova T., Li P.
      Arch. Biochem. Biophys. 488:23-33(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 893-1017 IN COMPLEX WITH ZINC IONS.
    30. "Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors."
      Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.
      J. Biol. Chem. 284:17465-17474(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 896-1025 IN COMPLEX WITH ZINC IONS.
    31. "Human dech-box RNA helicase mda5 (melanoma differentiation-associated protein 5), dech-domain."
      Structural genomics consortium (SGC)
      Submitted (FEB-2009) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 277-490.

    Entry informationi

    Entry nameiIFIH1_HUMAN
    AccessioniPrimary (citable) accession number: Q9BYX4
    Secondary accession number(s): Q2NKL6
    , Q6DC96, Q86X56, Q96MX8, Q9H3G6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 12, 2005
    Last sequence update: March 20, 2007
    Last modified: October 1, 2014
    This is version 127 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    In HIV-1 infected HeLa-CD4 cells, overexpression of IFIH1 results in a great increase in the level of secreted viral p24 protein.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3