ID   ELF4_MOUSE              Reviewed;         655 AA.
AC   Q9Z2U4; B1AY67;
DT   21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=ETS-related transcription factor Elf-4;
DE   AltName: Full=E74-like factor 4;
DE   AltName: Full=Myeloid Elf-1-like factor;
GN   Name=Elf4 {ECO:0000312|MGI:MGI:1928377};
GN   Synonyms=Mef {ECO:0000312|EMBL:AAD01601.1};
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] {ECO:0000312|EMBL:AAD01601.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Miyazaki Y., De Blasio T., Nimer S.D.;
RT   "Murine MEF (myeloid elf-1-like factor) cDNA clone.";
RL   Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=12387738; DOI=10.1016/s1074-7613(02)00422-3;
RA   Lacorazza H.D., Miyazaki Y., Di Cristofano A., Deblasio A., Hedvat C.,
RA   Zhang J., Cordon-Cardo C., Mao S., Pandolfi P.P., Nimer S.D.;
RT   "The ETS protein MEF plays a critical role in perforin gene expression and
RT   the development of natural killer and NK-T cells.";
RL   Immunity 17:437-449(2002).
RN   [4]
RP   FUNCTION.
RX   PubMed=19380490; DOI=10.1128/mcb.01551-08;
RA   Sashida G., Liu Y., Elf S., Miyata Y., Ohyashiki K., Izumi M., Menendez S.,
RA   Nimer S.D.;
RT   "ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16
RT   activation to promote transformation.";
RL   Mol. Cell. Biol. 29:3687-3699(2009).
RN   [5]
RP   FUNCTION.
RX   PubMed=19412182; DOI=10.1038/ni.1730;
RA   Yamada T., Park C.S., Mamonkin M., Lacorazza H.D.;
RT   "Transcription factor ELF4 controls the proliferation and homing of CD8+ T
RT   cells via the Kruppel-like factors KLF4 and KLF2.";
RL   Nat. Immunol. 10:618-626(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Lung, and 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   [7]
RP   FUNCTION, AND MUTAGENESIS OF TRP-250.
RX   PubMed=34326534; DOI=10.1038/s41590-021-00984-4;
RA   Tyler P.M., Bucklin M.L., Zhao M., Maher T.J., Rice A.J., Ji W., Warner N.,
RA   Pan J., Morotti R., McCarthy P., Griffiths A., van Rossum A.M.C.,
RA   Hollink I.H.I.M., Dalm V.A.S.H., Catanzaro J., Lakhani S.A., Muise A.M.,
RA   Lucas C.L.;
RT   "Human autoinflammatory disease reveals ELF4 as a transcriptional regulator
RT   of inflammation.";
RL   Nat. Immunol. 22:1118-1126(2021).
RN   [8]
RP   FUNCTION, AND MUTAGENESIS OF TRP-230.
RX   PubMed=35266071; DOI=10.1007/s10875-022-01243-3;
RA   Sun G., Qiu L., Yu L., An Y., Ding Y., Zhou L., Wu J., Yang X., Zhang Z.,
RA   Tang X., Xia H., Cao L., You F., Zhao X., Du H.;
RT   "Loss of Function Mutation in ELF4 Causes Autoinflammatory and
RT   Immunodeficiency Disease in Human.";
RL   J. Clin. Immunol. 42:798-810(2022).
CC   -!- FUNCTION: Transcriptional activator that binds to DNA sequences
CC       containing the consensus 5'-WGGA-3'. Transactivates promoters of the
CC       hematopoietic growth factor genes CSF2, IL3, IL8, and of LYZ. Acts
CC       synergistically with RUNX1 to transactivate the IL3 promoter (By
CC       similarity). Transactivates the PRF1 promoter in natural killer (NK)
CC       cells and in CD8+ T cells (PubMed:34326534). Plays a role in the
CC       development and function of NK and NK T-cells and in innate immunity.
CC       Controls the proliferation and homing of CD8+ T-cells via the Kruppel-
CC       like factors KLF4 and KLF2. Controls cell senescence in a p53-dependent
CC       manner. Can also promote cellular transformation through inhibition of
CC       the p16 pathway. Is a transcriptional regulator of inflammation,
CC       controlling T-helper 17 (Th17) cells and macrophage inflammatory
CC       responses. Required for sustained transcription of anti-inflammatory
CC       genes, including IL1RN (PubMed:34326534, PubMed:35266071). Is a
CC       negative regulator of pro-inflammatory cytokines expression, including
CC       IL17A, IL1B, IL6, TNFA and CXCL1 (PubMed:34326534, PubMed:35266071).
CC       Down-regulates expression of TREM1, a cell surface receptor involved in
CC       the amplification of inflammatory responses (PubMed:34326534,
CC       PubMed:35266071). {ECO:0000250, ECO:0000269|PubMed:12387738,
CC       ECO:0000269|PubMed:19380490, ECO:0000269|PubMed:19412182,
CC       ECO:0000269|PubMed:34326534, ECO:0000269|PubMed:35266071}.
CC   -!- SUBUNIT: Interacts with RUNX1 (via the Runt domain); the interaction
CC       transactivates the IL3 promoter. Interacts (via its C-terminus) with
CC       PML; the interaction translocates ELF4 to PML nuclear bodies and
CC       enhances transactivation of LYZ (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250}.
CC       Note=Accumulation into PML nuclear bodies is mediated by PML.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ETS family. {ECO:0000255}.
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DR   EMBL; AF016714; AAD01601.1; -; mRNA.
DR   EMBL; AL844594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS30108.1; -.
DR   RefSeq; NP_062654.2; NM_019680.2.
DR   RefSeq; XP_006541589.1; XM_006541526.2.
DR   RefSeq; XP_006541590.1; XM_006541527.1.
DR   AlphaFoldDB; Q9Z2U4; -.
DR   SMR; Q9Z2U4; -.
DR   BioGRID; 208021; 1.
DR   STRING; 10090.ENSMUSP00000110608; -.
DR   iPTMnet; Q9Z2U4; -.
DR   PhosphoSitePlus; Q9Z2U4; -.
DR   EPD; Q9Z2U4; -.
DR   jPOST; Q9Z2U4; -.
DR   MaxQB; Q9Z2U4; -.
DR   PaxDb; 10090-ENSMUSP00000110608; -.
DR   ProteomicsDB; 275740; -.
DR   Antibodypedia; 16200; 476 antibodies from 30 providers.
DR   DNASU; 56501; -.
DR   Ensembl; ENSMUST00000033429.9; ENSMUSP00000033429.3; ENSMUSG00000031103.13.
DR   Ensembl; ENSMUST00000114958.8; ENSMUSP00000110608.2; ENSMUSG00000031103.13.
DR   GeneID; 56501; -.
DR   KEGG; mmu:56501; -.
DR   UCSC; uc009tce.2; mouse.
DR   AGR; MGI:1928377; -.
DR   CTD; 2000; -.
DR   MGI; MGI:1928377; Elf4.
DR   VEuPathDB; HostDB:ENSMUSG00000031103; -.
DR   eggNOG; KOG3804; Eukaryota.
DR   GeneTree; ENSGT00940000161870; -.
DR   HOGENOM; CLU_027279_1_0_1; -.
DR   InParanoid; Q9Z2U4; -.
DR   OMA; DDQEGHC; -.
DR   OrthoDB; 4245771at2759; -.
DR   PhylomeDB; Q9Z2U4; -.
DR   TreeFam; TF318679; -.
DR   BioGRID-ORCS; 56501; 5 hits in 80 CRISPR screens.
DR   ChiTaRS; Elf4; mouse.
DR   PRO; PR:Q9Z2U4; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; Q9Z2U4; Protein.
DR   Bgee; ENSMUSG00000031103; Expressed in granulocyte and 102 other cell types or tissues.
DR   ExpressionAtlas; Q9Z2U4; baseline and differential.
DR   GO; GO:0016604; C:nuclear body; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0016605; C:PML body; ISS: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; IBA:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0001787; P:natural killer cell proliferation; IDA:UniProtKB.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR   GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB.
DR   GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:UniProtKB.
DR   GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR   GO; GO:0001866; P:NK T cell proliferation; IDA:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR000418; Ets_dom.
DR   InterPro; IPR046328; ETS_fam.
DR   InterPro; IPR022084; TF_Elf_N.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR11849; ETS; 1.
DR   PANTHER; PTHR11849:SF170; ETS-RELATED TRANSCRIPTION FACTOR ELF-4; 1.
DR   Pfam; PF12310; Elf-1_N; 1.
DR   Pfam; PF00178; Ets; 1.
DR   PRINTS; PR00454; ETSDOMAIN.
DR   SMART; SM00413; ETS; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS00018; EF_HAND_1; 1.
DR   PROSITE; PS00345; ETS_DOMAIN_1; 1.
DR   PROSITE; PS00346; ETS_DOMAIN_2; 1.
DR   PROSITE; PS50061; ETS_DOMAIN_3; 1.
DR   Genevisible; Q9Z2U4; MM.
PE   1: Evidence at protein level;
KW   Activator; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..655
FT                   /note="ETS-related transcription factor Elf-4"
FT                   /id="PRO_0000204090"
FT   DNA_BIND        208..290
FT                   /note="ETS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00237"
FT   REGION          86..205
FT                   /note="RUNX1-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q99607"
FT   REGION          136..202
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          301..362
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          493..512
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        141..171
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        310..332
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        334..349
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         187
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99607"
FT   MOD_RES         633
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99607"
FT   MOD_RES         640
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99607"
FT   MUTAGEN         230
FT                   /note="W->R: Higher TNFA, IL1B and IL6 expression in bone
FT                   marrow-derived and peritoneal macrophages from mutant mice
FT                   compared to wild-type, after VSV infection. Decreased viral
FT                   clearance in mutant mice compared to wild-type. Loss of
FT                   transcriptional activity shown in IFNB1 promoter-driven
FT                   luciferase assay."
FT                   /evidence="ECO:0000269|PubMed:35266071"
FT   MUTAGEN         250
FT                   /note="W->S: Higher IL17A, IL1B, IL6, CXCL1 and TREM1
FT                   expression in bone marrow-derived macrophages from mutant
FT                   mice compared to wild-type, after LPS stimulation. CD8+ T
FT                   cells from mutant mice have reduced PRF1 expression when
FT                   activated with IL-2 compared to cells from wild-type
FT                   littermates."
FT                   /evidence="ECO:0000269|PubMed:34326534"
FT   CONFLICT        132
FT                   /note="N -> K (in Ref. 1; AAD01601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        146
FT                   /note="T -> A (in Ref. 1; AAD01601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="N -> S (in Ref. 1; AAD01601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        448
FT                   /note="Q -> A (in Ref. 1; AAD01601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        496
FT                   /note="S -> T (in Ref. 1; AAD01601)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   655 AA;  70800 MW;  44CAFA1D3D77153C CRC64;
     MAIALQPSDL VFEFASNGMD DIHQLEDPSV FPAVIVEQVP YPELVHLCSG LDLDEVHNGI
     IRDRTLCMTQ DQILEGSILL TDDDVSTSNN VSSTEVLFNV ATPSDVLDEK QIFSSPEVLS
     DSNSVQAINL PNFLLSTPEP DDLKKTSDAG DQKEHSEEEK VSREENLRKM GKARKRNRKT
     KNNRSTSPVT DPSMPIRKKS KDGKGSTIYL WEFLLALLQD RNTCPKYIKW TQREKGIFKL
     VDSKAVSKLW GKQKNKPDMN YETMGRALRY YYQRGILAKV EGQRLVYQFK EMPKDLVVID
     DEEESPETPE DSSQASTSST PSTSTIRRAS SRVGTRASPE DKDNPPWEKP KVQHTGLQPS
     ASLELGLSVD EEVPTTSTML ASPLQSQARL TKTVSSSPAP SNIHLGVAPV GPGSTVTLQT
     IPLTTVLTNG PPASTTAPTQ LVLQSVPQVS TFKDTFTLQT SFPLNTNLQE NQVATQGAPL
     ILSGLPQLLA GANPQSNPAP SQVIGAGSAG PSSQPPGTVI AAFIRTSSGT SVPVVKEGPL
     RSSSYVQGVV TGAPVEGLLV PEETLRELLR DQGHLQPLPS QVLSRGSHNL SLVGNQTLSP
     PSHPTVGLTP VAELELSSGS GPLFVTEPSV TRSPTQAPFS PFNPTSLIKM EPQDI
//