CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-020386
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Interferon-induced helicase C domain-containing protein 1 
Protein Synonyms/Alias
 Clinically amyopathic dermatomyositis autoantigen 140 kDa; CADM-140 autoantigen; Helicase with 2 CARD domains; Helicard; Interferon-induced with helicase C domain protein 1; Melanoma differentiation-associated protein 5; MDA-5; Murabutide down-regulated protein; RIG-I-like receptor 2; RLR-2; RNA helicase-DEAD box protein 116 
Gene Name
 IFIH1 
Gene Synonyms/Alias
 MDA5; RH116 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
137LVRDVLDKCMEEELLubiquitination[1]
174LLKRIVQKENWFSAFubiquitination[1, 2]
700NPEYENEKLTKLRNTubiquitination[1]
726ARGIIFTKTRQSAYAubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 7 97 CARD 1.
 DOMAIN 110 190 CARD 2.
 DOMAIN 316 509 Helicase ATP-binding.
 DOMAIN 700 882 Helicase C-terminal.
 METAL 907 907 Zinc.
 METAL 910 910 Zinc.
 METAL 962 962 Zinc.
 METAL 964 964 Zinc.
 MOD_RES 289 289 Phosphoserine (By similarity).
 MOD_RES 301 301 Phosphoserine (By similarity).
 MOD_RES 645 645 Phosphoserine (By similarity).  
Keyword
 3D-structure; Alternative splicing; Antiviral defense; ATP-binding; Complete proteome; Cytoplasm; Diabetes mellitus; Helicase; Host-virus interaction; Hydrolase; Immunity; Innate immunity; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; RNA-binding; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1025 AA 
Protein Sequence
MSNGYSTDEN FRYLISCFRA RVKMYIQVEP VLDYLTFLPA EVKEQIQRTV ATSGNMQAVE 60
LLLSTLEKGV WHLGWTREFV EALRRTGSPL AARYMNPELT DLPSPSFENA HDEYLQLLNL 120
LQPTLVDKLL VRDVLDKCME EELLTIEDRN RIAAAENNGN ESGVRELLKR IVQKENWFSA 180
FLNVLRQTGN NELVQELTGS DCSESNAEIE NLSQVDGPQV EEQLLSTTVQ PNLEKEVWGM 240
ENNSSESSFA DSSVVSESDT SLAEGSVSCL DESLGHNSNM GSDSGTMGSD SDEENVAARA 300
SPEPELQLRP YQMEVAQPAL EGKNIIICLP TGSGKTRVAV YIAKDHLDKK KKASEPGKVI 360
VLVNKVLLVE QLFRKEFQPF LKKWYRVIGL SGDTQLKISF PEVVKSCDII ISTAQILENS 420
LLNLENGEDA GVQLSDFSLI IIDECHHTNK EAVYNNIMRH YLMQKLKNNR LKKENKPVIP 480
LPQILGLTAS PGVGGATKQA KAEEHILKLC ANLDAFTIKT VKENLDQLKN QIQEPCKKFA 540
IADATREDPF KEKLLEIMTR IQTYCQMSPM SDFGTQPYEQ WAIQMEKKAA KEGNRKERVC 600
AEHLRKYNEA LQINDTIRMI DAYTHLETFY NEEKDKKFAV IEDDSDEGGD DEYCDGDEDE 660
DDLKKPLKLD ETDRFLMTLF FENNKMLKRL AENPEYENEK LTKLRNTIME QYTRTEESAR 720
GIIFTKTRQS AYALSQWITE NEKFAEVGVK AHHLIGAGHS SEFKPMTQNE QKEVISKFRT 780
GKINLLIATT VAEEGLDIKE CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVAHSGSGV 840
IEHETVNDFR EKMMYKAIHC VQNMKPEEYA HKILELQMQS IMEKKMKTKR NIAKHYKNNP 900
SLITFLCKNC SVLACSGEDI HVIEKMHHVN MTPEFKELYI VRENKALQKK CADYQINGEI 960
ICKCGQAWGT MMVHKGLDLP CLKIRNFVVV FKNNSTKKQY KKWVELPITF PNLDYSECCL 1020
FSDED 1025 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003677; F:DNA binding; IEA:InterPro.
 GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
 GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
 GO:0043021; F:ribonucleoprotein complex binding; IPI:UniProtKB.
 GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0039528; P:cytoplasmic pattern recognition receptor signaling pathway in response to virus; TAS:UniProtKB.
 GO:0009597; P:detection of virus; TAS:BHF-UCL.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
 GO:0032727; P:positive regulation of interferon-alpha production; IMP:UniProtKB.
 GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
 GO:0016925; P:protein sumoylation; IDA:UniProtKB.
 GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
 GO:0034344; P:regulation of type III interferon production; TAS:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 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. 
Pfam
 PF00619; CARD
 PF00271; Helicase_C
 PF04851; ResIII
 PF11648; RIG-I_C-RD 
SMART
 SM00487; DEXDc
 SM00490; HELICc 
PROSITE
 PS50209; CARD
 PS51192; HELICASE_ATP_BIND_1
 PS51194; HELICASE_CTER 
PRINTS