GenomeNet

Database: UniProt
Entry: Q4JF28
LinkDB: Q4JF28
Original site: Q4JF28 
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   01-OCT-2014, entry version 81.
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 which plays a critical role in
CC       the innate immune response against DNA and RNA viruses. Regulates
CC       the 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, is 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). {ECO:0000250}.
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. {ECO:0000250}.
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 rotavirus A NSP1 (via C-terminus); this interaction
CC       leads to the proteasome-dependent degradation of IRF3. Interacts
CC       with RBCK1. Interacts with TRIM21. Interacts with HERC5. InteractS
CC       with DDX3X; the interaction allows the phosphorylation and
CC       activation of IRF3 by IKBKE (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC       {ECO:0000250}. 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). {ECO:0000250}.
CC   -!- PTM: Constitutively phosphorylated on many Ser/Thr residues. C-
CC       terminal serine/threonine cluster is phosphorylated in response of
CC       induction by IKBKE and TBK1. Phosphorylated at Ser-392 by IKBKE
CC       upon ssRNA viral infection. Phosphorylation at Ser-382 by TBK1
CC       results in oligomerization (By similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated; ubiquitination involves RBCK1 leading to
CC       proteasomal degradation. Polyubiquitinated; ubiquitination
CC       involves TRIM21 leading to proteasomal degradation (By
CC       similarity). {ECO:0000250}.
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). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00840}.
CC   -!- SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding
CC       domain. {ECO:0000255|PROSITE-ProRule:PRU00840}.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
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   RefSeq; NP_001025016.1; NM_001029845.3.
DR   RefSeq; XP_005219329.1; XM_005219272.1.
DR   UniGene; Bt.45332; -.
DR   ProteinModelPortal; Q4JF28; -.
DR   SMR; Q4JF28; 1-112, 185-417.
DR   IntAct; Q4JF28; 1.
DR   PRIDE; Q4JF28; -.
DR   Ensembl; ENSBTAT00000031869; ENSBTAP00000031815; ENSBTAG00000006633.
DR   GeneID; 516979; -.
DR   KEGG; bta:516979; -.
DR   CTD; 3661; -.
DR   eggNOG; NOG42868; -.
DR   GeneTree; ENSGT00740000115254; -.
DR   HOGENOM; HOG000033705; -.
DR   HOVERGEN; HBG105601; -.
DR   InParanoid; Q4JF28; -.
DR   KO; K05411; -.
DR   OMA; CHTYWAV; -.
DR   OrthoDB; EOG7CCBR1; -.
DR   TreeFam; TF328512; -.
DR   Reactome; REACT_203575; IRF3 mediated activation of type 1 IFN.
DR   Reactome; REACT_205128; TRAF3-dependent IRF activation pathway.
DR   Reactome; REACT_205585; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR   Reactome; REACT_211149; Negative regulators of RIG-I/MDA5 signaling.
DR   Reactome; REACT_215067; Factors involved in megakaryocyte development and platelet production.
DR   Reactome; REACT_215264; ISG15 antiviral mechanism.
DR   Reactome; REACT_218986; TRAF6 mediated IRF7 activation.
DR   Reactome; REACT_219559; IRF3-mediated induction of type I IFN.
DR   Reactome; REACT_221627; LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
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:Ensembl.
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:Ensembl.
DR   GO; GO:0050689; P:negative regulation of defense response to virus by host; IEA:Ensembl.
DR   GO; GO:0045358; P:negative regulation of interferon-beta biosynthetic process; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
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:Ensembl.
DR   GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   GO; GO:0045351; P:type I interferon biosynthetic process; IEA:Ensembl.
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; SSF49879; 1.
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                                {ECO:0000255|PROSITE-ProRule:PRU00840}.
FT   REGION      196    356       Involved in HERC5 binding. {ECO:0000250}.
FT   MOD_RES       3      3       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES      14     14       Phosphoserine. {ECO:0000250}.
FT   MOD_RES      75     75       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES      97     97       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     184    184       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     249    249       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES     382    382       Phosphoserine; by TBK1. {ECO:0000250}.
FT   MOD_RES     392    392       Phosphoserine; by IKKE. {ECO:0000250}.
FT   MOD_RES     394    394       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     400    400       Phosphothreonine. {ECO:0000250}.
FT   CROSSLNK    189    189       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ISG15).
FT                                {ECO:0000250}.
FT   CROSSLNK    356    356       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ISG15).
FT                                {ECO:0000250}.
FT   CROSSLNK    362    362       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ISG15).
FT                                {ECO:0000250}.
FT   CONFLICT     56     59       AWAV -> VRAE (in Ref. 2; AAZ38325).
FT                                {ECO:0000305}.
FT   CONFLICT    100    101       SQ -> PH (in Ref. 2; AAZ38325).
FT                                {ECO:0000305}.
FT   CONFLICT    115    117       RDI -> GDF (in Ref. 2; AAZ38325).
FT                                {ECO:0000305}.
FT   CONFLICT    130    130       N -> S (in Ref. 2; AAZ38325).
FT                                {ECO:0000305}.
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
//
DBGET integrated database retrieval system