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}.
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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 Genevisible; Q64287; MM.
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.
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
//
