ID   IRF4_MOUSE              Reviewed;         450 AA.
AC   Q64287; Q60802;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   24-JAN-2024, entry version 192.
DE   RecName: Full=Interferon regulatory factor 4;
DE            Short=IRF-4;
DE   AltName: Full=Lymphocyte-specific interferon regulatory factor;
DE            Short=LSIRF;
DE   AltName: Full=NF-EM5;
DE   AltName: Full=PU.1 interaction partner;
DE   AltName: Full=Transcriptional activator PIP;
GN   Name=Irf4; Synonyms=Spip;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=7797077; DOI=10.1101/gad.9.11.1377;
RA   Eisenbeis C.F., Singh H., Storb U.;
RT   "Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent
RT   transcriptional activator.";
RL   Genes Dev. 9:1377-1387(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   STRAIN=129/SvJ, and C57BL/6J; TISSUE=Spleen;
RX   PubMed=7541907; DOI=10.1093/nar/23.12.2127;
RA   Matsuyama T., Grossman A., Mittruecker H.-W., Siderovski D.P., Kiefer F.,
RA   Kawakami T., Richardson C.D., Taniguchi T., Yoshinaga S.K., Mak T.W.;
RT   "Molecular cloning of LSIRF, a lymphoid-specific member of the interferon
RT   regulatory factor family that binds the interferon-stimulated response
RT   element (ISRE).";
RL   Nucleic Acids Res. 23:2127-2136(1995).
RN   [3]
RP   PROTEIN SEQUENCE OF 65-72, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [4]
RP   PHOSPHORYLATION AT SER-446 AND SER-447.
RX   PubMed=20697158; DOI=10.1172/jci42856;
RA   Biswas P.S., Gupta S., Chang E., Song L., Stirzaker R.A., Liao J.K.,
RA   Bhagat G., Pernis A.B.;
RT   "Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and
RT   the development of autoimmunity in mice.";
RL   J. Clin. Invest. 120:3280-3295(2010).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH BATF.
RX   PubMed=22992524; DOI=10.1038/nature11531;
RA   Tussiwand R., Lee W.L., Murphy T.L., Mashayekhi M., Kc W., Albring J.C.,
RA   Satpathy A.T., Rotondo J.A., Edelson B.T., Kretzer N.M., Wu X., Weiss L.A.,
RA   Glasmacher E., Li P., Liao W., Behnke M., Lam S.S., Aurthur C.T.,
RA   Leonard W.J., Singh H., Stallings C.L., Sibley L.D., Schreiber R.D.,
RA   Murphy K.M.;
RT   "Compensatory dendritic cell development mediated by BATF-IRF
RT   interactions.";
RL   Nature 490:502-507(2012).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH BATF.
RX   PubMed=22992523; DOI=10.1038/nature11530;
RA   Li P., Spolski R., Liao W., Wang L., Murphy T.L., Murphy K.M.,
RA   Leonard W.J.;
RT   "BATF-JUN is critical for IRF4-mediated transcription in T cells.";
RL   Nature 490:543-546(2012).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH BATF.
RX   PubMed=22983707; DOI=10.1126/science.1228309;
RA   Glasmacher E., Agrawal S., Chang A.B., Murphy T.L., Zeng W.,
RA   Vander Lugt B., Khan A.A., Ciofani M., Spooner C., Rutz S., Hackney J.,
RA   Nurieva R., Escalante C.R., Ouyang W., Littman D.R., Murphy K.M., Singh H.;
RT   "A genomic regulatory element that directs assembly and function of immune-
RT   specific AP-1-IRF complexes.";
RL   Science 338:975-980(2012).
RN   [8]
RP   INTERACTION WITH NLRP3.
RX   PubMed=26098997; DOI=10.1038/ni.3202;
RA   Bruchard M., Rebe C., Derangere V., Togbe D., Ryffel B., Boidot R.,
RA   Humblin E., Hamman A., Chalmin F., Berger H., Chevriaux A., Limagne E.,
RA   Apetoh L., Vegran F., Ghiringhelli F.;
RT   "The receptor NLRP3 is a transcriptional regulator of TH2
RT   differentiation.";
RL   Nat. Immunol. 16:859-870(2015).
CC   -!- FUNCTION: Transcriptional activator. Binds to the interferon-stimulated
CC       response element (ISRE) of the MHC class I promoter. Binds the
CC       immunoglobulin lambda light chain enhancer, together with PU.1.
CC       Probably plays a role in ISRE-targeted signal transduction mechanisms
CC       specific to lymphoid cells. Involved in CD8(+) dendritic cell
CC       differentiation by forming a complex with the BATF-JUNB heterodimer in
CC       immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-
CC       3'), an immune-specific regulatory element, followed by cooperative
CC       binding of BATF and IRF4 and activation of genes.
CC       {ECO:0000269|PubMed:22983707, ECO:0000269|PubMed:22992523,
CC       ECO:0000269|PubMed:22992524}.
CC   -!- SUBUNIT: Interacts with SPIB and DEF6 (By similarity). Interacts with
CC       the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the
CC       interaction is direct. Directly interacts with NLRP3 in the nucleus of
CC       Th2 cells; this interaction enhances IRF4 ability to bind to the IL4
CC       promoter and is required for optimal IRF4-dependent IL4 transcription
CC       (PubMed:26098997). Interacts with SPI1 (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:Q15306, ECO:0000269|PubMed:22983707,
CC       ECO:0000269|PubMed:22992523, ECO:0000269|PubMed:22992524,
CC       ECO:0000269|PubMed:26098997}.
CC   -!- INTERACTION:
CC       Q64287; O35284: Batf; NbExp=7; IntAct=EBI-6398485, EBI-6398523;
CC       Q64287; O70343: Ppargc1a; NbExp=6; IntAct=EBI-6398485, EBI-1371053;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q64287-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q64287-2; Sequence=VSP_002756;
CC   -!- TISSUE SPECIFICITY: Lymphoid cells.
CC   -!- INDUCTION: Not induced by interferons.
CC   -!- PTM: Phosphorylation by ROCK2 regulates IL-17 and IL-21 production.
CC       {ECO:0000269|PubMed:20697158}.
CC   -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00840}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U34307; AAA75283.1; -; mRNA.
DR   EMBL; U11692; AAA75309.1; -; mRNA.
DR   EMBL; U20949; AAA75316.1; -; Genomic_DNA.
DR   EMBL; U20949; AAA75317.1; -; Genomic_DNA.
DR   CCDS; CCDS26419.1; -. [Q64287-1]
DR   CCDS; CCDS84017.1; -. [Q64287-2]
DR   PIR; S57837; S57837.
DR   RefSeq; NP_001334437.1; NM_001347508.1. [Q64287-2]
DR   RefSeq; NP_038702.1; NM_013674.2. [Q64287-1]
DR   PDB; 5BVI; X-ray; 2.60 A; A/B=238-420.
DR   PDBsum; 5BVI; -.
DR   AlphaFoldDB; Q64287; -.
DR   SMR; Q64287; -.
DR   BioGRID; 200786; 7.
DR   CORUM; Q64287; -.
DR   DIP; DIP-59740N; -.
DR   IntAct; Q64287; 6.
DR   STRING; 10090.ENSMUSP00000021784; -.
DR   iPTMnet; Q64287; -.
DR   PhosphoSitePlus; Q64287; -.
DR   EPD; Q64287; -.
DR   MaxQB; Q64287; -.
DR   PaxDb; 10090-ENSMUSP00000021784; -.
DR   ProteomicsDB; 268993; -. [Q64287-1]
DR   ProteomicsDB; 268994; -. [Q64287-2]
DR   Antibodypedia; 1057; 767 antibodies from 47 providers.
DR   DNASU; 16364; -.
DR   Ensembl; ENSMUST00000021784.10; ENSMUSP00000021784.3; ENSMUSG00000021356.11. [Q64287-1]
DR   Ensembl; ENSMUST00000110307.3; ENSMUSP00000105936.2; ENSMUSG00000021356.11. [Q64287-2]
DR   GeneID; 16364; -.
DR   KEGG; mmu:16364; -.
DR   UCSC; uc007pyz.1; mouse. [Q64287-1]
DR   AGR; MGI:1096873; -.
DR   CTD; 3662; -.
DR   MGI; MGI:1096873; Irf4.
DR   VEuPathDB; HostDB:ENSMUSG00000021356; -.
DR   eggNOG; ENOG502QUE4; Eukaryota.
DR   GeneTree; ENSGT00940000159059; -.
DR   HOGENOM; CLU_031544_1_1_1; -.
DR   InParanoid; Q64287; -.
DR   OMA; DHIQEQN; -.
DR   OrthoDB; 3740806at2759; -.
DR   PhylomeDB; Q64287; -.
DR   TreeFam; TF328512; -.
DR   BioGRID-ORCS; 16364; 2 hits in 81 CRISPR screens.
DR   PRO; PR:Q64287; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; Q64287; Protein.
DR   Bgee; ENSMUSG00000021356; Expressed in mesenteric lymph node and 56 other cell types or tissues.
DR   ExpressionAtlas; Q64287; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0000786; C:nucleosome; IDA:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IMP:ARUK-UCL.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:ARUK-UCL.
DR   GO; GO:0006338; P:chromatin remodeling; IMP:MGI.
DR   GO; GO:0042832; P:defense response to protozoan; IMP:UniProtKB.
DR   GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR   GO; GO:0043011; P:myeloid dendritic cell differentiation; IMP:UniProtKB.
DR   GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IMP:MGI.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:ARUK-UCL.
DR   GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR   GO; GO:0032736; P:positive regulation of interleukin-13 production; ISS:UniProtKB.
DR   GO; GO:0032743; P:positive regulation of interleukin-2 production; ISS:UniProtKB.
DR   GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0072540; P:T-helper 17 cell lineage commitment; IMP:UniProtKB.
DR   CDD; cd00103; IRF; 1.
DR   Gene3D; 2.60.200.10; -; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR019817; Interferon_reg_fac_CS.
DR   InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR   InterPro; IPR019471; Interferon_reg_factor-3.
DR   InterPro; IPR017855; SMAD-like_dom_sf.
DR   InterPro; IPR008984; SMAD_FHA_dom_sf.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR11949; INTERFERON REGULATORY FACTOR; 1.
DR   PANTHER; PTHR11949:SF6; INTERFERON REGULATORY FACTOR 4; 1.
DR   Pfam; PF00605; IRF; 1.
DR   Pfam; PF10401; IRF-3; 1.
DR   PRINTS; PR00267; INTFRNREGFCT.
DR   SMART; SM00348; IRF; 1.
DR   SMART; SM01243; IRF-3; 1.
DR   SUPFAM; SSF49879; SMAD/FHA domain; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS00601; IRF_1; 1.
DR   PROSITE; PS51507; IRF_2; 1.
DR   Genevisible; Q64287; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Alternative splicing; Direct protein sequencing;
KW   DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..450
FT                   /note="Interferon regulatory factor 4"
FT                   /id="PRO_0000154557"
FT   DNA_BIND        21..129
FT                   /note="IRF tryptophan pentad repeat"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT   MOD_RES         446
FT                   /note="Phosphoserine; by ROCK2"
FT                   /evidence="ECO:0000269|PubMed:20697158"
FT   MOD_RES         447
FT                   /note="Phosphoserine; by ROCK2"
FT                   /evidence="ECO:0000269|PubMed:20697158"
FT   VAR_SEQ         165
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_002756"
FT   HELIX           241..248
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          252..258
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          261..267
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          274..279
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          286..291
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          297..300
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   HELIX           301..308
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          315..319
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          321..328
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          330..332
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          334..338
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          343..345
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          355..360
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   HELIX           361..374
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          383..388
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   STRAND          400..407
FT                   /evidence="ECO:0007829|PDB:5BVI"
FT   HELIX           408..418
FT                   /evidence="ECO:0007829|PDB:5BVI"
SQ   SEQUENCE   450 AA;  51577 MW;  5FD94CA6C453869C CRC64;
     MNLETGSRGS EFGMSAVSCG NGKLRQWLID QIDSGKYPGL VWENEEKSVF RIPWKHAGKQ
     DYNREEDAAL FKAWALFKGK FREGIDKPDP PTWKTRLRCA LNKSNDFEEL VERSQLDISD
     PYKVYRIVPE GAKKGAKQLT LDDTQMAMGH PYPMTAPYGS LPAQQVHNYM MPPHDRSWRD
     YAPDQSHPEI PYQCPVTFGP RGHHWQGPSC ENGCQVTGTF YACAPPESQA PGIPIEPSIR
     SAEALALSDC RLHICLYYRD ILVKELTTTS PEGCRISHGH TYDVSNLDQV LFPYPDDNGQ
     RKNIEKLLSH LERGLVLWMA PDGLYAKRLC QSRIYWDGPL ALCSDRPNKL ERDQTCKLFD
     TQQFLSELQV FAHHGRPAPR FQVTLCFGEE FPDPQRQRKL ITAHVEPLLA RQLYYFAQQN
     TGHFLRGYEL PEHVTTPDYH RSLRHSSIQE
//