IRF5_MOUSE
ID IRF5_MOUSE Reviewed; 497 AA.
AC P56477;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Interferon regulatory factor 5 {ECO:0000303|PubMed:15665823, ECO:0000303|PubMed:18824541};
DE Short=IRF-5 {ECO:0000303|PubMed:15665823, ECO:0000303|PubMed:18824541};
GN Name=Irf5 {ECO:0000303|PubMed:15665823, ECO:0000303|PubMed:18824541,
GN ECO:0000312|MGI:MGI:1350924};
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=C57BL/6J; TISSUE=Lymph node;
RA Grossman A., Kondo S., Antonio L., Mak T.W.;
RT "Generation of mutant mice deficient in IRF5.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MYD88 AND TRAF6, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=15665823; DOI=10.1038/nature03308;
RA Takaoka A., Yanai H., Kondo S., Duncan G., Negishi H., Mizutani T.,
RA Kano S., Honda K., Ohba Y., Mak T.W., Taniguchi T.;
RT "Integral role of IRF-5 in the gene induction programme activated by Toll-
RT like receptors.";
RL Nature 434:243-249(2005).
RN [3]
RP UBIQUITINATION AT LYS-410 AND LYS-411 BY TRAF6, AND SUBCELLULAR LOCATION.
RX PubMed=18824541; DOI=10.1128/mcb.00662-08;
RA Balkhi M.Y., Fitzgerald K.A., Pitha P.M.;
RT "Functional regulation of MyD88-activated interferon regulatory factor 5 by
RT K63-linked polyubiquitination.";
RL Mol. Cell. Biol. 28:7296-7308(2008).
RN [4]
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 [5]
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, SUBUNIT, PHOSPHORYLATION AT
RP SER-430; SER-434; SER-436 AND SER-445, AND MUTAGENESIS OF SER-434 AND
RP SER-445.
RX PubMed=25326420; DOI=10.1073/pnas.1418516111;
RA Ren J., Chen X., Chen Z.J.;
RT "IKKbeta is an IRF5 kinase that instigates inflammation.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:17438-17443(2014).
CC -!- FUNCTION: Transcription factor that plays a critical role in innate
CC immunity by activating expression of type I interferon (IFN) IFNA and
CC INFB and inflammatory cytokines downstream of endolysosomal toll-like
CC receptors TLR7, TLR8 and TLR9 (PubMed:15665823). Regulates the
CC transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-
CC stimulated genes (ISG) by binding to an interferon-stimulated response
CC element (ISRE) in their promoters (PubMed:15665823). Can efficiently
CC activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and
CC mediate their induction downstream of the TLR-activated, MyD88-
CC dependent pathway (PubMed:15665823). {ECO:0000269|PubMed:15665823}.
CC -!- ACTIVITY REGULATION: Maintained as a monomer in an autoinhibited state
CC (PubMed:25326420). Phosphorylation and activation follow the following
CC steps: innate adapter protein TASL recruits IRF5, thereby licensing
CC IRF5 for phosphorylation by IKBKB (By similarity). Phosphorylated IRF5
CC dissociates from the adapter proteins, dimerizes, and then enters the
CC nucleus to induce IFNs (PubMed:25326420).
CC {ECO:0000250|UniProtKB:Q13568, ECO:0000269|PubMed:25326420}.
CC -!- SUBUNIT: Homodimer, when phosphorylated (PubMed:25326420). Interacts
CC with TASL (via pLxIS motif); interaction takes place downstream of
CC TLR7, TLR8 or TLR9, leading to its activation (By similarity).
CC Interacts with MYD88 and TRAF6 (PubMed:15665823).
CC {ECO:0000250|UniProtKB:Q13568, ECO:0000269|PubMed:15665823,
CC ECO:0000269|PubMed:25326420}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15665823,
CC ECO:0000269|PubMed:18824541, ECO:0000269|PubMed:25326420}. Nucleus
CC {ECO:0000269|PubMed:15665823, ECO:0000269|PubMed:18824541,
CC ECO:0000269|PubMed:25326420}. Note=Shuttles between the nucleus and the
CC cytoplasm: upon activation by the TLR adapter MYD88 and subsequent
CC phosphorylation, translocates to the nucleus.
CC {ECO:0000269|PubMed:15665823, ECO:0000269|PubMed:25326420}.
CC -!- PTM: Phosphorylation of serine and threonine residues by IKBKB in a C-
CC terminal autoinhibitory region, stimulates dimerization, transport into
CC the nucleus, assembly with the coactivator CBP/EP300 and initiation of
CC transcription. {ECO:0000269|PubMed:25326420}.
CC -!- PTM: 'Lys-63'-linked polyubiquitination by TRAF6 is required for
CC activation. {ECO:0000269|PubMed:18824541}.
CC -!- DISRUPTION PHENOTYPE: Mice develop normally and no overt phenotype is
CC observed in hematopoietic cell population (PubMed:15665823). However,
CC the induction of pro-inflammatory cytokines, such as interleukin-6
CC (IL6) and IL12 by various TLR ligands is impaired, whereas interferon-
CC alpha induction is normal (PubMed:15665823).
CC {ECO:0000269|PubMed:15665823}.
CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC ProRule:PRU00840}.
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DR EMBL; AF028725; AAB81997.1; -; mRNA.
DR CCDS; CCDS19962.1; -.
DR RefSeq; NP_001239311.1; NM_001252382.1.
DR RefSeq; NP_036187.1; NM_012057.4.
DR RefSeq; XP_006505160.1; XM_006505097.1.
DR AlphaFoldDB; P56477; -.
DR SMR; P56477; -.
DR BioGRID; 205111; 5.
DR DIP; DIP-49382N; -.
DR IntAct; P56477; 4.
DR STRING; 10090.ENSMUSP00000004392; -.
DR iPTMnet; P56477; -.
DR PhosphoSitePlus; P56477; -.
DR PaxDb; P56477; -.
DR PeptideAtlas; P56477; -.
DR PRIDE; P56477; -.
DR ProteomicsDB; 269332; -.
DR Antibodypedia; 17820; 640 antibodies from 45 providers.
DR DNASU; 27056; -.
DR Ensembl; ENSMUST00000004392; ENSMUSP00000004392; ENSMUSG00000029771.
DR Ensembl; ENSMUST00000163511; ENSMUSP00000127021; ENSMUSG00000029771.
DR GeneID; 27056; -.
DR KEGG; mmu:27056; -.
DR UCSC; uc009bdu.2; mouse.
DR CTD; 3663; -.
DR MGI; MGI:1350924; Irf5.
DR VEuPathDB; HostDB:ENSMUSG00000029771; -.
DR eggNOG; ENOG502QSKM; Eukaryota.
DR GeneTree; ENSGT00940000159926; -.
DR HOGENOM; CLU_031544_0_0_1; -.
DR InParanoid; P56477; -.
DR OMA; HHIWQAQ; -.
DR OrthoDB; 648909at2759; -.
DR PhylomeDB; P56477; -.
DR TreeFam; TF328512; -.
DR BioGRID-ORCS; 27056; 4 hits in 76 CRISPR screens.
DR PRO; PR:P56477; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P56477; protein.
DR Bgee; ENSMUSG00000029771; Expressed in mesenteric lymph node and 145 other tissues.
DR ExpressionAtlas; P56477; baseline and differential.
DR Genevisible; P56477; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISO:MGI.
DR GO; GO:0032494; P:response to peptidoglycan; ISO:MGI.
DR CDD; cd00103; IRF; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.200.10; -; 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; IPR029838; IRF5.
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:SF10; PTHR11949:SF10; 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; SSF46785; SSF46785; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS00601; IRF_1; 1.
DR PROSITE; PS51507; IRF_2; 1.
PE 1: Evidence at protein level;
KW Antiviral defense; Cytoplasm; DNA-binding; Immunity; Inflammatory response;
KW Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..497
FT /note="Interferon regulatory factor 5"
FT /id="PRO_0000154559"
FT DNA_BIND 14..122
FT /note="IRF tryptophan pentad repeat"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT REGION 124..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 12..18
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q13568"
FT MOTIF 149..159
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q13568"
FT COMPBIAS 135..149
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q13568"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13568"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25326420"
FT MOD_RES 434
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000269|PubMed:25326420"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25326420"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13568"
FT MOD_RES 445
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000269|PubMed:25326420"
FT CROSSLNK 410
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18824541"
FT CROSSLNK 411
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18824541"
FT MUTAGEN 434
FT /note="S->A: Reduced homodimerization and subsequent
FT activation."
FT /evidence="ECO:0000269|PubMed:25326420"
FT MUTAGEN 445
FT /note="S->A: Abolished homodimerization and subsequent
FT activation."
FT /evidence="ECO:0000269|PubMed:25326420"
SQ SEQUENCE 497 AA; 56005 MW; D8BD54DB946E354F CRC64;
MNHSAPGIPP PPRRVRLKPW LVAQVNSCQY PGLQWVNGEK KLFYIPWRHA TRHGPSQDGD
NTIFKAWAKE TGKYTEGVDE ADPAKWKANL RCALNKSRDF QLFYDGPRDM PPQPYKIYEV
CSNGPAPTES QPTDDYVLGE EEEEEEEELQ RMLPGLSITE PALPGPPNAP YSLPKEDTKW
PPALQPPVGL GPPVPDPNLL APPSGNPAGF RQLLPEVLEP GPLASSQPPT EPLLPDLLIS
PHMLPLTDLE IKFQYRGRAP RTLTISNPQG CRLFYSQLEA TQEQVELFGP VTLEQVRFPS
PEDIPSDKQR FYTNQLLDVL DRGLILQLQG QDLYAIRLCQ CKVFWSGPCA LAHGSCPNPI
QREVKTKLFS LEQFLNELIL FQKGQTNTPP PFEIFFCFGE EWPDVKPREK KLITVQVVPV
AARLLLEMFS GELSWSADSI RLQISNPDLK DHMVEQFKEL HHLWQSQQQL QPMVQAPPVA
GLDASQGPWP MHPVGMQ
