CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012354
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Interferon regulatory factor 3 
Protein Synonyms/Alias
 IRF-3 
Gene Name
 IRF3 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
70AYVPGRDKPDLPTWKubiquitination[1]
87FRSALNRKEGLRLAEsumoylation[2]
193GPSENPLKRLLVPGEubiquitination[3, 4, 5]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation.
 Ran Y, Liu TT, Zhou Q, Li S, Mao AP, Li Y, Liu LJ, Cheng JK, Shu HB.
 J Mol Cell Biol. 2011 Oct;3(5):283-92. [PMID: 22028379]
 [3] 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]
 [4] 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]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages. 
Sequence Annotation
 DNA_BIND 5 111 IRF tryptophan pentad repeat.
 REGION 200 360 Involved in HERC5 binding.
 MOTIF 139 149 Nuclear export signal.
 MOD_RES 123 123 Phosphoserine (By similarity).
 DISULFID 267 289
 CROSSLNK 193 193 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 360 360 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 366 366 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Activator; Alternative splicing; Antiviral defense; Complete proteome; Cytoplasm; Disulfide bond; DNA-binding; Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 427 AA 
Protein Sequence
MGTPKPRILP WLVSQLDLGQ LEGVAWVNKS RTRFRIPWKH GLRQDAQQED FGIFQAWAEA 60
TGAYVPGRDK PDLPTWKRNF RSALNRKEGL RLAEDRSKDP HDPHKIYEFV NSGVGDFSQP 120
DTSPDTNGGG STSDTQEDIL DELLGNMVLA PLPDPGPPSL AVAPEPCPQP LRSPSLDNPT 180
PFPNLGPSEN PLKRLLVPGE EWEFEVTAFY RGRQVFQQTI SCPEGLRLVG SEVGDRTLPG 240
WPVTLPDPGM SLTDRGVMSY VRHVLSCLGG GLALWRAGQW LWAQRLGHCH TYWAVSEELL 300
PNSGHGPDGE VPKDKEGGVF DLGPFIVDLI TFTEGSGRSP RYALWFCVGE SWPQDQPWTK 360
RLVMVKVVPT CLRALVEMAR VGGASSLENT VDLHISNSHP LSLTSDQYKA YLQDLVEGMD 420
FQGPGES 427 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0003677; F:DNA binding; NAS:BHF-UCL.
 GO:0000975; F:regulatory region DNA binding; IEA:InterPro.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
 GO:0003712; F:transcription cofactor activity; TAS:ProtInc.
 GO:0006917; P:induction of apoptosis; TAS:UniProtKB.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0071888; P:macrophage apoptotic process; TAS:UniProtKB.
 GO:0039530; P:MDA-5 signaling pathway; TAS:UniProtKB.
 GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
 GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
 GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
 GO:0006974; P:response to DNA damage stimulus; TAS:UniProtKB.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR019817; Interferon_reg_fac_CS.
 IPR001346; Interferon_reg_fact_DNA-bd_dom.
 IPR019471; Interferon_reg_factor-3.
 IPR017855; SMAD_dom-like.
 IPR008984; SMAD_FHA_domain.
 IPR011991; WHTH_DNA-bd_dom. 
Pfam
 PF00605; IRF
 PF10401; IRF-3 
SMART
 SM00348; IRF 
PROSITE
 PS00601; IRF_1
 PS51507; IRF_2 
PRINTS
 PR00267; INTFRNREGFCT.