ID IRF3_BOVIN Reviewed; 417 AA.
AC Q4JF28; A8W7A8; Q45VM9;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 29-MAY-2013, entry version 74.
DE RecName: Full=Interferon regulatory factor 3;
DE Short=IRF-3;
GN Name=IRF3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC Pecora; Bovidae; Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RA Yang W., Seyfert H.M.;
RT "Dissection of MyD88 dependent and independent TLR-mediated signal
RT transduction in mammary epithelial cells of the cow.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Werling D.;
RT "Stimulation of the MyD88-independent pathway in bovine antigen
RT presenting cells.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Goodbourn S., Moganeradj K., McCauley J.;
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Key transcriptional regulator of type I interferon
CC (IFN)-dependent immune responses and plays a critical role in the
CC innate immune response against DNA and RNA viruses. Regulates the
CC transcription of type I IFN genes (IFN-alpha and IFN-beta) and
CC IFN-stimulated genes (ISG) by binding to an interferon-stimulated
CC response element (ISRE) in their promoters. Acts as a more potent
CC activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA)
CC gene and plays a critical role in both the early and late phases
CC of the IFNA/B gene induction. Found in an inactive form in the
CC cytoplasm of uninfected cells and following viral infection,
CC double-stranded RNA (dsRNA), or toll-like receptor (TLR)
CC signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This
CC induces a conformational change, leading to its dimerization and
CC nuclear localization and association with CREB binding protein
CC (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which
CC activates the transcription of the type I IFN and ISG genes. Can
CC activate distinct gene expression programs in macrophages and can
CC induce significant apoptosis in primary macrophages (By
CC similarity).
CC -!- ENZYME REGULATION: In the absence of viral infection, maintained
CC as a monomer in an autoinhibited state and phosphorylation
CC disrupts this autoinhibition leading to the liberation of the DNA-
CC binding and dimerization activities and its nuclear localization
CC where it can activate type I IFN and ISG genes (By similarity).
CC -!- SUBUNIT: Monomer. Homodimer; phosphorylation-induced. Heterodimer
CC with IRF7. Interacts with CREBBP. May interact with MAVS.
CC Interacts with IKBKE and TBK1. Interacts with TICAM1 and TICAM2.
CC Interacts with RBCK1. Interacts with TRIM21. Interacts with HERC5
CC (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity). Note=Shuttles between cytoplasmic and nuclear
CC compartments, with export being the prevailing effect. When
CC activated, IRF3 interaction with CREBBP prevents its export to the
CC cytoplasm (By similarity).
CC -!- PTM: Constitutively phosphorylated on many serines residues. C-
CC terminal serine/threonine cluster is phosphorylated in response of
CC induction by IKBKE and TBK1 (By similarity).
CC -!- PTM: Ubiquitinated; ubiquitination involves RBCK1 leading to
CC proteasomal degradation. Polyubiquitinated; ubiquitination
CC involves TRIM21 leading to proteasomal degradation (By
CC similarity).
CC -!- PTM: ISGylated by HERC5 resulting in sustained IRF3 activation and
CC in the inhibition of IRF3 ubiquitination by disrupting PIN1
CC binding. The phosphorylation state of IRF3 does not alter
CC ISGylation (By similarity).
CC -!- SIMILARITY: Belongs to the IRF family.
CC -!- SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding
CC domain.
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DR EMBL; AJ879589; CAI53672.1; -; mRNA.
DR EMBL; DQ103889; AAZ38325.1; -; mRNA.
DR EMBL; EU194377; ABW74073.1; -; mRNA.
DR EMBL; BC102119; AAI02120.1; -; mRNA.
DR IPI; IPI00713562; -.
DR RefSeq; NP_001025016.1; NM_001029845.3.
DR UniGene; Bt.45332; -.
DR ProteinModelPortal; Q4JF28; -.
DR SMR; Q4JF28; 1-112, 185-417.
DR PRIDE; Q4JF28; -.
DR Ensembl; ENSBTAT00000031869; ENSBTAP00000031815; ENSBTAG00000006633.
DR GeneID; 516979; -.
DR KEGG; bta:516979; -.
DR CTD; 3661; -.
DR eggNOG; NOG42868; -.
DR GeneTree; ENSGT00670000097873; -.
DR HOGENOM; HOG000033705; -.
DR HOVERGEN; HBG105601; -.
DR InParanoid; Q4JF28; -.
DR KO; K05411; -.
DR OMA; EGVAWLD; -.
DR OrthoDB; EOG4X6C90; -.
DR BioCyc; CATTLE:516979-MONOMER; -.
DR NextBio; 20872344; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:Compara.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
DR GO; GO:0050689; P:negative regulation of defense response to virus by host; IEA:Compara.
DR GO; GO:0045358; P:negative regulation of interferon-beta biosynthetic process; IEA:Compara.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IEA:Compara.
DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Compara.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0045351; P:type I interferon biosynthetic process; IEA:Compara.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.200.10; -; 1.
DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR InterPro; IPR019471; Interferon_reg_factor-3.
DR InterPro; IPR017855; SMAD_dom-like.
DR InterPro; IPR008984; SMAD_FHA_domain.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF00605; IRF; 1.
DR Pfam; PF10401; IRF-3; 1.
DR PRINTS; PR00267; INTFRNREGFCT.
DR SMART; SM00348; IRF; 1.
DR SUPFAM; SSF49879; SMAD_FHA; 1.
DR PROSITE; PS00601; IRF_1; FALSE_NEG.
DR PROSITE; PS51507; IRF_2; 1.
PE 2: Evidence at transcript level;
KW Activator; Antiviral defense; Complete proteome; Cytoplasm;
KW DNA-binding; Immunity; Innate immunity; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 417 Interferon regulatory factor 3.
FT /FTId=PRO_0000223675.
FT DNA_BIND 5 111 IRF tryptophan pentad repeat.
FT REGION 196 356 Involved in HERC5 binding (By
FT similarity).
FT MOD_RES 123 123 Phosphoserine (By similarity).
FT CROSSLNK 189 189 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ISG15) (By
FT similarity).
FT CROSSLNK 356 356 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ISG15) (By
FT similarity).
FT CROSSLNK 362 362 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ISG15) (By
FT similarity).
FT CONFLICT 56 59 AWAV -> VRAE (in Ref. 2; AAZ38325).
FT CONFLICT 100 101 SQ -> PH (in Ref. 2; AAZ38325).
FT CONFLICT 115 117 RDI -> GDF (in Ref. 2; AAZ38325).
FT CONFLICT 130 130 N -> S (in Ref. 2; AAZ38325).
SQ SEQUENCE 417 AA; 46646 MW; 06ADC5BCCD4D6389 CRC64;
MGTQKPRILP WLISQLDRGE LEGVAWLGES RTRFRIPWKH GLRQDAQQED FGIFQAWAVA
SGAYTPGKDK PDLPTWKRNF RSALNRKEVL RLAEDHSKDS QDPHKIYEFV NSGVRDIPEP
DTSQDNGRHN TSDTQEDTLE KLLSDMDLSP GGPSNLTMAS EKPPQFLQSP DSDIPALCPN
SGLSENPLKQ LLANEEDWEF EVTAFYRGCQ VFQQTVFCPG GLRLVGSEAG DRMLPGQPIR
LPDPATSLTD KSVTDYVQRV LSCLGGGLAL WRAGQWLCAQ RLGHCHVYWA IGEELLPSCG
HKPDGEVPKD REGGVFNLGP FITDLITFIE GSRRSPLYTL WFCVGQSWPQ DQPWIKRLVM
VKVVPMCLRV LVDIARQGGA SSLENTVDLH ISNSDPLSLT PDQYMACLQD LAEDMDF
//
