ID   IRF8_MOUSE              Reviewed;         424 AA.
AC   P23611;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Interferon regulatory factor 8 {ECO:0000303|PubMed:17579016};
DE            Short=IRF-8 {ECO:0000303|PubMed:17579016};
DE   AltName: Full=Interferon consensus sequence-binding protein {ECO:0000303|PubMed:2111015};
DE            Short=ICSBP {ECO:0000303|PubMed:2111015};
GN   Name=Irf8 {ECO:0000303|PubMed:17579016, ECO:0000312|MGI:MGI:96395};
GN   Synonyms=Icsbp {ECO:0000303|PubMed:2111015}, Icsbp1;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=2111015; DOI=10.1073/pnas.87.10.3743;
RA   Driggers P.H., Ennist D.L., Gleason S.L., Mak W.-H., Marks M.S.,
RA   Levi B.-Z., Flanagan J.R., Appella E., Ozato K.;
RT   "An interferon gamma-regulated protein that binds the interferon-inducible
RT   enhancer element of major histocompatibility complex class I genes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:3743-3747(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Colon;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=12461077; DOI=10.1084/jem.20021263;
RA   Schiavoni G., Mattei F., Sestili P., Borghi P., Venditti M.,
RA   Morse H.C. III, Belardelli F., Gabriele L.;
RT   "ICSBP is essential for the development of mouse type I interferon-
RT   producing cells and for the generation and activation of CD8alpha(+)
RT   dendritic cells.";
RL   J. Exp. Med. 196:1415-1425(2002).
RN   [5]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=12393690; DOI=10.1182/blood-2002-04-1088;
RA   Aliberti J., Schulz O., Pennington D.J., Tsujimura H., Reis e Sousa C.,
RA   Ozato K., Sher A.;
RT   "Essential role for ICSBP in the in vivo development of murine CD8alpha +
RT   dendritic cells.";
RL   Blood 101:305-310(2003).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=12538667; DOI=10.4049/jimmunol.170.3.1131;
RA   Tsujimura H., Tamura T., Ozato K.;
RT   "IFN consensus sequence binding protein/IFN regulatory factor 8 drives the
RT   development of type I IFN-producing plasmacytoid dendritic cells.";
RL   J. Immunol. 170:1131-1135(2003).
RN   [7]
RP   INTERACTION WITH TRIM21, UBIQUITINATION, INDUCTION, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=17579016; DOI=10.4049/jimmunol.179.1.26;
RA   Kong H.J., Anderson D.E., Lee C.H., Jang M.K., Tamura T., Tailor P.,
RA   Cho H.K., Cheong J., Xiong H., Morse H.C. III, Ozato K.;
RT   "Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates
RT   IRF-8 and enhances cytokine expression in macrophages.";
RL   J. Immunol. 179:26-30(2007).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [9]
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   [10]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=23382217; DOI=10.1073/pnas.1222798110;
RA   Baccala R., Gonzalez-Quintial R., Blasius A.L., Rimann I., Ozato K.,
RA   Kono D.H., Beutler B., Theofilopoulos A.N.;
RT   "Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid
RT   dendritic cells in the pathogenesis of lupus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:2940-2945(2013).
RN   [11]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=32741026; DOI=10.1096/fj.202001197r;
RA   Jeong E., Kim J., Go M., Lee S.Y.;
RT   "Early estrogen-induced gene 1 facilitates osteoclast formation through the
RT   inhibition of interferon regulatory factor 8 expression.";
RL   FASEB J. 34:12894-12906(2020).
CC   -!- FUNCTION: Transcription factor that specifically binds to the upstream
CC       regulatory region of type I interferon (IFN) and IFN-inducible MHC
CC       class I genes (the interferon consensus sequence (ICS))
CC       (PubMed:2111015, PubMed:12393690). Can both act as a transcriptional
CC       activator or repressor (PubMed:2111015). Plays a negative regulatory
CC       role in cells of the immune system (PubMed:2111015). Involved in CD8(+)
CC       dendritic cell differentiation by forming a complex with the BATF-JUNB
CC       heterodimer in immune cells, leading to recognition of AICE sequence
CC       (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed
CC       by cooperative binding of BATF and IRF8 and activation of genes
CC       (PubMed:12393690, PubMed:22992524). Required for the development of
CC       plasmacytoid dendritic cells (pDCs), which produce most of the type I
CC       IFN in response to viral infection (PubMed:12461077, PubMed:12393690,
CC       PubMed:12538667, PubMed:23382217). Positively regulates macroautophagy
CC       in dendritic cells (By similarity). Acts as a transcriptional repressor
CC       of osteoclast differentiation factors such as NFATC1 and EEIG1
CC       (PubMed:32741026). {ECO:0000250|UniProtKB:Q02556,
CC       ECO:0000269|PubMed:12393690, ECO:0000269|PubMed:12461077,
CC       ECO:0000269|PubMed:12538667, ECO:0000269|PubMed:2111015,
CC       ECO:0000269|PubMed:22992524, ECO:0000269|PubMed:23382217,
CC       ECO:0000269|PubMed:32741026}.
CC   -!- SUBUNIT: Interacts with COPS2 (By similarity). Interacts (via C-
CC       terminus) with TRIM21 (via C-terminus). Interacts with the BATF-JUNB
CC       heterodimer. Interacts with BATF (via bZIP domain); the interaction is
CC       direct. Interacts with SPI1 (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:Q02556, ECO:0000269|PubMed:17579016,
CC       ECO:0000269|PubMed:22992524}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17579016}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q02556}. Note=In resting macrophages, localizes
CC       in the cytoplasm. Translocated in the nucleus upon IFN-gamma induction.
CC       {ECO:0000250|UniProtKB:Q02556}.
CC   -!- TISSUE SPECIFICITY: Expressed in bone marrow macrophages (at protein
CC       level) (PubMed:32741026). Mainly expressed in lymphoid tissues
CC       (PubMed:2111015). Predominantly expressed in CD8(+)-expressing
CC       dendritic cells (PubMed:12393690). {ECO:0000269|PubMed:12393690,
CC       ECO:0000269|PubMed:2111015, ECO:0000269|PubMed:32741026}.
CC   -!- INDUCTION: By interferon gamma. {ECO:0000269|PubMed:17579016}.
CC   -!- PTM: Ubiquitinated (PubMed:17579016). Ubiquitination by TRIM21 in
CC       macrophages, a process that is strongly increased upon interferon gamma
CC       stimulation, leds to the enhanced transcriptional activity of target
CC       cytokine genes (PubMed:17579016). Ubiquitination leads to its
CC       degradation by the proteasome (By similarity).
CC       {ECO:0000250|UniProtKB:Q02556, ECO:0000269|PubMed:17579016}.
CC   -!- PTM: Sumoylated with SUMO3. Desumoylated by SENP1.
CC       {ECO:0000250|UniProtKB:Q02556}.
CC   -!- DISRUPTION PHENOTYPE: Mice display an absence of interferon (IFN)-
CC       producing cells and show impaired IFN production in response to viral
CC       infection (PubMed:12461077). Complete absence of plasmacytoid dendritic
CC       cells (pDCs) and conventional CD8(+)-expressing dendritic cells (cDCs)
CC       (PubMed:12393690, PubMed:12538667, PubMed:23382217). Mice display
CC       reduced autoimmunity (PubMed:23382217). {ECO:0000269|PubMed:12393690,
CC       ECO:0000269|PubMed:12461077, ECO:0000269|PubMed:12538667,
CC       ECO:0000269|PubMed:23382217}.
CC   -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00840}.
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DR   EMBL; M32489; AAA37878.1; -; mRNA.
DR   EMBL; AK018533; BAB31258.1; -; mRNA.
DR   EMBL; BC005450; AAH05450.1; -; mRNA.
DR   CCDS; CCDS22721.1; -.
DR   PIR; A35861; A35861.
DR   RefSeq; NP_001288740.1; NM_001301811.1.
DR   RefSeq; NP_032346.1; NM_008320.4.
DR   AlphaFoldDB; P23611; -.
DR   SMR; P23611; -.
DR   BioGRID; 200504; 6.
DR   CORUM; P23611; -.
DR   IntAct; P23611; 1.
DR   STRING; 10090.ENSMUSP00000040245; -.
DR   iPTMnet; P23611; -.
DR   PhosphoSitePlus; P23611; -.
DR   SwissPalm; P23611; -.
DR   EPD; P23611; -.
DR   PaxDb; 10090-ENSMUSP00000040245; -.
DR   PeptideAtlas; P23611; -.
DR   ProteomicsDB; 267007; -.
DR   Antibodypedia; 1058; 508 antibodies from 42 providers.
DR   DNASU; 15900; -.
DR   Ensembl; ENSMUST00000047737.10; ENSMUSP00000040245.4; ENSMUSG00000041515.11.
DR   Ensembl; ENSMUST00000162001.8; ENSMUSP00000125029.2; ENSMUSG00000041515.11.
DR   GeneID; 15900; -.
DR   KEGG; mmu:15900; -.
DR   UCSC; uc009nrk.2; mouse.
DR   AGR; MGI:96395; -.
DR   CTD; 3394; -.
DR   MGI; MGI:96395; Irf8.
DR   VEuPathDB; HostDB:ENSMUSG00000041515; -.
DR   eggNOG; ENOG502QT9P; Eukaryota.
DR   GeneTree; ENSGT00940000158140; -.
DR   HOGENOM; CLU_031544_1_1_1; -.
DR   InParanoid; P23611; -.
DR   OMA; SSYEQYH; -.
DR   OrthoDB; 3740806at2759; -.
DR   PhylomeDB; P23611; -.
DR   TreeFam; TF328512; -.
DR   BioGRID-ORCS; 15900; 1 hit in 79 CRISPR screens.
DR   ChiTaRS; Irf8; mouse.
DR   PRO; PR:P23611; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; P23611; Protein.
DR   Bgee; ENSMUSG00000041515; Expressed in ileal epithelium and 177 other cell types or tissues.
DR   ExpressionAtlas; P23611; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI.
DR   GO; GO:0071346; P:cellular response to type II interferon; ISS:UniProtKB.
DR   GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR   GO; GO:0042832; P:defense response to protozoan; IMP:MGI.
DR   GO; GO:0097028; P:dendritic cell differentiation; IMP:UniProtKB.
DR   GO; GO:0002316; P:follicular B cell differentiation; IGI:ARUK-UCL.
DR   GO; GO:0002314; P:germinal center B cell differentiation; IGI:ARUK-UCL.
DR   GO; GO:0006955; P:immune response; IMP:UniProtKB.
DR   GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR   GO; GO:0030099; P:myeloid cell differentiation; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0006909; P:phagocytosis; IMP:MGI.
DR   GO; GO:0002273; P:plasmacytoid dendritic cell differentiation; IMP:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IPI:MGI.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:ARUK-UCL.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; IMP:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0032479; P:regulation of type I interferon production; IMP:UniProtKB.
DR   GO; GO:0009617; P:response to bacterium; IMP:MGI.
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:SF7; INTERFERON REGULATORY FACTOR 8; 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; P23611; MM.
PE   1: Evidence at protein level;
KW   Activator; Autophagy; Cytoplasm; DNA-binding; Nucleus; Reference proteome;
KW   Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT   CHAIN           1..424
FT                   /note="Interferon regulatory factor 8"
FT                   /id="PRO_0000154565"
FT   DNA_BIND        7..114
FT                   /note="IRF tryptophan pentad repeat"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
SQ   SEQUENCE   424 AA;  48237 MW;  FBE79A76846E8EB2 CRC64;
     MCDRNGGRRL RQWLIEQIDS SMYPGLIWEN DEKTMFRIPW KHAGKQDYNQ EVDASIFKAW
     AVFKGKFKEG DKAEPATWKT RLRCALNKSP DFEEVTDRSQ LDISEPYKVY RIVPEEEQKC
     KLGVAPAGCM SEVPEMECGR SEIEELIKEP SVDEYMGMTK RSPSPPEACR SQILPDWWVQ
     QPSAGLPLVT GYAAYDTHHS AFSQMVISFY YGGKLVGQAT TTCLEGCRLS LSQPGLPKLY
     GPDGLEPVCF PTADTIPSER QRQVTRKLFG HLERGVLLHS NRKGVFVKRL CQGRVFCSGN
     AVVCKGRPNK LERDEVVQVF DTNQFIRELQ QFYATQSRLP DSRVVLCFGE EFPDTVPLRS
     KLILVQVEQL YARQLVEEAG KSCGAGSLMP ALEEPQPDQA FRMFPDICTS HQRPFFRENQ
     QITV
//