CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009968
UniProt Accession
Genbank Protein ID
 U73037 
Genbank Nucleotide ID
Protein Name
 Interferon regulatory factor 7 
Protein Synonyms/Alias
 IRF-7 
Gene Name
 Irf7 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
59EEDAQIFKAWAVARGubiquitination[1]
406EKTLILVKLEPWVCKsumoylation[2, 3]
413KLEPWVCKAYLEGVQubiquitination[1]
Reference
 [1] 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]
 [2] 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]
 [3] 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] 
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. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88- independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists 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 where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages. 
Sequence Annotation
 DNA_BIND 9 126 IRF tryptophan pentad repeat.
 MOD_RES 92 92 N6-acetyllysine; by KAT2A and KAT2B (By
 MOD_RES 425 425 Phosphoserine (Probable).
 MOD_RES 426 426 Phosphoserine (Probable).
 MOD_RES 429 429 Phosphoserine (Probable).
 MOD_RES 431 431 Phosphoserine; by TBK1 and IKKE (By
 MOD_RES 437 437 Phosphoserine (Probable).
 MOD_RES 438 438 Phosphoserine (Probable).
 CROSSLNK 398 398 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 400 400 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Activator; 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
 457 AA 
Protein Sequence
MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL DEEDAQIFKA 60
WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH STGRFILRQD NSGDPVDPHK 120
VYELSRELGS TVGPATENRE EVSLSNALPT QGVSPGSFLA RENAGLQTPS PLLSSDAGDL 180
LLQVLQYSHI LESESGADPV PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL 240
GFLDVTIMYK GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT 300
ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL ERNRHTPIFD 360
FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK TLILVKLEPW VCKAYLEGVQ 420
REGVSSLDSS SLGLCLSSTN SLYEDIEHFL MDLGQWP 457 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0003677; F:DNA binding; ISS:UniProtKB.
 GO:0000982; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Compara.
 GO:0016064; P:immunoglobulin mediated immune response; IMP:MGI.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0032607; P:interferon-alpha production; IMP:UniProtKB.
 GO:0032608; P:interferon-beta production; IMP:UniProtKB.
 GO:0032727; P:positive regulation of interferon-alpha production; TAS:UniProtKB.
 GO:0032728; P:positive regulation of interferon-beta production; TAS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:MGI.
 GO:0006473; P:protein acetylation; IEA:Compara.
 GO:0006468; P:protein phosphorylation; IEA:Compara.
 GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
 GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; IMP:UniProtKB.
 GO:0034127; P:regulation of MyD88-independent toll-like receptor signaling pathway; IMP:UniProtKB.
 GO:0045351; P:type I interferon biosynthetic process; IMP: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.