CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009988
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
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
152GLILGPLKDEGSSDLsumoylation[1, 2, 3]
366KVVPTCLKELLEMARubiquitination[4]
Reference
 [1] Virus infection triggers SUMOylation of IRF3 and IRF7, leading to the negative regulation of type I interferon gene expression.
 Kubota T, Matsuoka M, Chang TH, Tailor P, Sasaki T, Tashiro M, Kato A, Ozato K.
 J Biol Chem. 2008 Sep 12;283(37):25660-70. [PMID: 18635538]
 [2] PIASy inhibits virus-induced and interferon-stimulated transcription through distinct mechanisms.
 Kubota T, Matsuoka M, Xu S, Otsuki N, Takeda M, Kato A, Ozato K.
 J Biol Chem. 2011 Mar 11;286(10):8165-75. [PMID: 21199872]
 [3] 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]
 [4] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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.
 MOD_RES 123 123 Phosphoserine.
 MOD_RES 135 135 Phosphoserine.
 CROSSLNK 188 188 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 353 353 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 359 359 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 Activator; Antiviral defense; Complete proteome; Cytoplasm; DNA-binding; Immunity; Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 419 AA 
Protein Sequence
METPKPRILP WLVSQLDLGQ LEGVAWLDES RTRFRIPWKH GLRQDAQMAD FGIFQAWAEA 60
SGAYTPGKDK PDVSTWKRNF RSALNRKEVL RLAADNSKDP YDPHKVYEFV TPGARDFVHL 120
GASPDTNGKS SLPHSQENLP KLFDGLILGP LKDEGSSDLA IVSDPSQQLP SPNVNNFLNP 180
APQENPLKQL LAEEQWEFEV TAFYRGRQVF QQTLFCPGGL RLVGSTADMT LPWQPVTLPD 240
PEGFLTDKLV KEYVGQVLKG LGNGLALWQA GQCLWAQRLG HSHAFWALGE ELLPDSGRGP 300
DGEVHKDKDG AVFDLRPFVA DLIAFMEGSG HSPRYTLWFC MGEMWPQDQP WVKRLVMVKV 360
VPTCLKELLE MAREGGASSL KTVDLHISNS QPISLTSDQY KAYLQDLVED MDFQATGNI 419 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:MGI.
 GO:0042803; F:protein homodimerization activity; IDA:MGI.
 GO:0000975; F:regulatory region DNA binding; IEA:InterPro.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:MGI.
 GO:0071359; P:cellular response to dsRNA; IEA:Compara.
 GO:0051607; P:defense response to virus; IMP:UniProtKB.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
 GO:0050689; P:negative regulation of defense response to virus by host; IDA:MGI.
 GO:0045358; P:negative regulation of interferon-beta biosynthetic process; IDA:MGI.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI.
 GO:0050715; P:positive regulation of cytokine secretion; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Compara.
 GO:0032727; P:positive regulation of interferon-alpha production; IMP:UniProtKB.
 GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
 GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:MGI.
 GO:0043330; P:response to exogenous dsRNA; IDA:MGI.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0045351; P:type I interferon biosynthetic process; IGI:MGI. 
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.