ID SPI1_MOUSE Reviewed; 272 AA. AC P17433; Q99L57; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 2. DT 27-MAR-2024, entry version 203. DE RecName: Full=Transcription factor PU.1 {ECO:0000303|PubMed:2180582}; DE AltName: Full=31 kDa-transforming protein; DE AltName: Full=SFFV proviral integration 1 protein; GN Name=Spi1; Synonyms=Sfpi-1 {ECO:0000303|PubMed:1985210}, Sfpi1; 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], AND INVOLVEMENT IN ERYTHROLEUKEMIA. RC STRAIN=ICFW; RX PubMed=2594367; RA Moreau-Gachelin F., Ray D., Mattei M.-G., Tambourin P., Tavitian A.; RT "The putative oncogene Spi-1: murine chromosomal localization and RT transcriptional activation in murine acute erythroleukemias."; RL Oncogene 4:1449-1456(1989). RN [2] RP ERRATUM OF PUBMED:2594367, AND SEQUENCE REVISION. RA Moreau-Gachelin F., Ray D., Mattei M.-G., Tambourin P., Tavitian A.; RL Oncogene 5:941-941(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=2180582; DOI=10.1016/0092-8674(90)90219-5; RA Klemsz M.J., McKercher S.R., Celada A., van Beveren C., Maki R.A.; RT "The macrophage and B cell-specific transcription factor PU.1 is related to RT the ets oncogene."; RL Cell 61:113-124(1990). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=1985210; DOI=10.1128/jvi.65.1.464-467.1991; RA Paul R., Schuetze S., Kozak S.L., Kozak C.A., Kabat D.; RT "The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the RT ets-related transcription factor Pu.1."; RL J. Virol. 65:464-467(1991). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; 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 [6] RP INTERACTION WITH CEBPD. RX PubMed=7594592; RA Nagulapalli S., Pongubala J.M., Atchison M.L.; RT "Multiple proteins physically interact with PU.1. Transcriptional synergy RT with NF-IL6 beta (C/EBP delta, CRP3)."; RL J. Immunol. 155:4330-4338(1995). RN [7] RP RNA-BINDING, FUNCTION, AND INTERACTION WITH NONO. RX PubMed=8626664; DOI=10.1074/jbc.271.19.11177; RA Hallier M., Tavitian A., Moreau-Gachelin F.; RT "The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA- RT binding protein p54nrb."; RL J. Biol. Chem. 271:11177-11181(1996). RN [8] RP INTERACTION WITH GFI1. RX PubMed=17197705; DOI=10.1074/jbc.m607613200; RA Dahl R., Iyer S.R., Owens K.S., Cuylear D.D., Simon M.C.; RT "The transcriptional repressor GFI-1 antagonizes PU.1 activity through RT protein-protein interaction."; RL J. Biol. Chem. 282:6473-6483(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=8079170; DOI=10.1126/science.8079170; RA Scott E.W., Simon M.C., Anastasi J., Singh H.; RT "Requirement of transcription factor PU.1 in the development of multiple RT hematopoietic lineages."; RL Science 265:1573-1577(1994). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 171-259 IN COMPLEX WITH DNA. RX PubMed=8602247; DOI=10.1038/380456a0; RA Kodandapani R., Pio F., Ni C.-Z., Piccialli G., Klemsz M., McKercher S., RA Maki R.A., Ely K.R.; RT "A new pattern for helix-turn-helix recognition revealed by the PU.1 ETS- RT domain-DNA complex."; RL Nature 380:456-460(1996). CC -!- FUNCTION: Pioneer transcription factor, which controls hematopoietic CC cell fate by decompacting stem cell heterochromatin and allowing other CC transcription factors to enter otherwise inaccessible genomic sites CC (PubMed:8079170). Once in open chromatin, can directly control gene CC expression by binding genetic regulatory elements and can also more CC broadly influence transcription by recruiting transcription factors, CC such as interferon regulatory factors (IRFs), to otherwise inaccessible CC genomic regions (By similarity). Transcriptionally activates genes CC important for myeloid and lymphoid lineages, such as CSF1R (By CC similarity). Transcriptional activation from certain promoters, CC possibly containing low affinity binding sites, is achieved CC cooperatively with other transcription factors. FCER1A transactivation CC is achieved in cooperation with GATA1 (By similarity). May be CC particularly important for the pro- to pre-B cell transition CC (PubMed:8079170). Binds (via the ETS domain) onto the purine-rich DNA CC core sequence 5'-GAGGAA-3', also known as the PU-box (PubMed:2180582). CC In vitro can bind RNA and interfere with pre-mRNA splicing CC (PubMed:8626664). {ECO:0000250|UniProtKB:P17947, CC ECO:0000250|UniProtKB:Q6BDS1, ECO:0000269|PubMed:2180582, CC ECO:0000269|PubMed:8079170, ECO:0000269|PubMed:8626664}. CC -!- ACTIVITY REGULATION: Transcriptional activity at macrophage-specific CC genes is inhibited by interaction with GFI1, which results in CC inhibition of SPI1-induced macrophage differentiation of myeloid CC progenitor cells, but not that of the granulocyte lineage. CC {ECO:0000269|PubMed:17197705}. CC -!- SUBUNIT: Binds DNA as a monomer. Can form homomers (By similarity). CC Directly interacts with CEBPD/NF-IL6-beta; this interaction does not CC affect DNA-binding properties of each partner (PubMed:7594592). CC Interacts with NONO/p54(nrb) (PubMed:8626664). Interacts with CC RUNX1/AML1 (By similarity). Interacts with GFI1; the interaction CC represses SPI1 transcriptional activity, hence blocks SPI1-induced CC macrophage differentiation of myeloid progenitor cells CC (PubMed:17197705). Interacts with CEBPE (By similarity). Interacts with CC IRF4/Pip and IRF8 (By similarity). Interacts with JUN (By similarity). CC Interacts with RB1 (By similarity). Interacts with TBP (By similarity). CC {ECO:0000250|UniProtKB:P17947, ECO:0000269|PubMed:17197705, CC ECO:0000269|PubMed:7594592, ECO:0000269|PubMed:8626664}. CC -!- INTERACTION: CC P17433; P70338: Gfi1; NbExp=2; IntAct=EBI-607588, EBI-3954754; CC P17433; Q99K48: Nono; NbExp=3; IntAct=EBI-607588, EBI-607499; CC P17433; Q99684: GFI1; Xeno; NbExp=2; IntAct=EBI-607588, EBI-949368; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P17947}. CC -!- TISSUE SPECIFICITY: Expressed in spleen, thymus and bone-marrow CC macrophages. {ECO:0000269|PubMed:1985210, ECO:0000269|PubMed:2180582}. CC -!- DISEASE: Note=May be involved in murine acute Friend erythroleukemia. CC It is a target region for SFFV proviral insertion. CC {ECO:0000269|PubMed:1985210, ECO:0000269|PubMed:2594367}. CC -!- DISRUPTION PHENOTYPE: Knockout embryos die at a late gestational stage, CC with no viable embryo after day 18 of gestation. Mutant embryos produce CC normal numbers of megakaryocytes and erythroid progenitors, but some CC show an impairment of erythroblast maturation. They exhibit a CC multilineage defect in the generation of progenitors for B and T CC lymphocytes, monocytes and granulocytes. {ECO:0000269|PubMed:8079170}. CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB59699.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA35502.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; X17463; CAA35502.1; ALT_INIT; mRNA. DR EMBL; L03215; AAB59699.1; ALT_INIT; mRNA. DR EMBL; M32370; AAA40024.1; -; mRNA. DR EMBL; M38252; AAA40110.1; -; mRNA. DR EMBL; BC003815; AAH03815.1; -; mRNA. DR CCDS; CCDS16425.1; -. DR PIR; A34693; A34693. DR RefSeq; NP_035485.1; NM_011355.2. DR PDB; 1PUE; X-ray; 2.10 A; E/F=171-259. DR PDB; 5W3G; NMR; -; A=167-272. DR PDB; 8EVH; EM; 2.85 A; O=1-272. DR PDB; 8EVI; EM; 2.64 A; O=1-272. DR PDB; 8EVJ; EM; 4.10 A; O=1-272. DR PDB; 8SMH; X-ray; 1.37 A; F=167-272. DR PDB; 8SMJ; X-ray; 1.39 A; F=167-272. DR PDB; 8SP1; X-ray; 1.62 A; F=167-265. DR PDBsum; 1PUE; -. DR PDBsum; 5W3G; -. DR PDBsum; 8EVH; -. DR PDBsum; 8EVI; -. DR PDBsum; 8EVJ; -. DR PDBsum; 8SMH; -. DR PDBsum; 8SMJ; -. DR PDBsum; 8SP1; -. DR AlphaFoldDB; P17433; -. DR EMDB; EMD-28629; -. DR EMDB; EMD-28630; -. DR EMDB; EMD-28631; -. DR SMR; P17433; -. DR BioGRID; 203184; 16. DR CORUM; P17433; -. DR IntAct; P17433; 8. DR STRING; 10090.ENSMUSP00000002180; -. DR iPTMnet; P17433; -. DR PhosphoSitePlus; P17433; -. DR PaxDb; 10090-ENSMUSP00000002180; -. DR PeptideAtlas; P17433; -. DR ProteomicsDB; 257319; -. DR Antibodypedia; 26734; 633 antibodies from 44 providers. DR DNASU; 20375; -. DR Ensembl; ENSMUST00000002180.8; ENSMUSP00000002180.8; ENSMUSG00000002111.9. DR GeneID; 20375; -. DR KEGG; mmu:20375; -. DR UCSC; uc008kuj.1; mouse. DR AGR; MGI:98282; -. DR CTD; 6688; -. DR MGI; MGI:98282; Spi1. DR VEuPathDB; HostDB:ENSMUSG00000002111; -. DR eggNOG; KOG3805; Eukaryota. DR GeneTree; ENSGT00940000159754; -. DR HOGENOM; CLU_066451_0_0_1; -. DR InParanoid; P17433; -. DR OMA; SYLPRMY; -. DR OrthoDB; 3980839at2759; -. DR PhylomeDB; P17433; -. DR TreeFam; TF352494; -. DR BioGRID-ORCS; 20375; 10 hits in 81 CRISPR screens. DR ChiTaRS; Spi1; mouse. DR EvolutionaryTrace; P17433; -. DR PRO; PR:P17433; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P17433; Protein. DR Bgee; ENSMUSG00000002111; Expressed in granulocyte and 151 other cell types or tissues. DR ExpressionAtlas; P17433; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI. DR GO; GO:0003682; F:chromatin binding; IMP:ARUK-UCL. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:ARUK-UCL. DR GO; GO:0003677; F:DNA binding; IDA:BHF-UCL. DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ARUK-UCL. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:ARUK-UCL. DR GO; GO:0001217; F:DNA-binding transcription repressor activity; ISO:MGI. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:ARUK-UCL. DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI. DR GO; GO:0051525; F:NFAT protein binding; IPI:BHF-UCL. DR GO; GO:0140311; F:protein sequestering activity; IMP:ARUK-UCL. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:0097677; F:STAT family protein binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI. DR GO; GO:0060033; P:anatomical structure regression; IMP:MGI. DR GO; GO:1902262; P:apoptotic process involved in blood vessel morphogenesis; IMP:MGI. DR GO; GO:0002357; P:defense response to tumor cell; ISO:MGI. DR GO; GO:0098508; P:endothelial to hematopoietic transition; IEP:ARUK-UCL. DR GO; GO:0030218; P:erythrocyte differentiation; IMP:MGI. 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:0030851; P:granulocyte differentiation; IDA:MGI. DR GO; GO:0002327; P:immature B cell differentiation; IGI:ARUK-UCL. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISO:MGI. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:ARUK-UCL. DR GO; GO:0030098; P:lymphocyte differentiation; IDA:MGI. DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IMP:MGI. DR GO; GO:0030225; P:macrophage differentiation; IDA:MGI. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IMP:MGI. DR GO; GO:0002573; P:myeloid leukocyte differentiation; IMP:MGI. DR GO; GO:1904178; P:negative regulation of adipose tissue development; IMP:ARUK-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:ARUK-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; IDA:BHF-UCL. DR GO; GO:0043314; P:negative regulation of neutrophil degranulation; IMP:ARUK-UCL. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0120186; P:negative regulation of protein localization to chromatin; IMP:ARUK-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0090402; P:oncogene-induced cell senescence; IDA:ARUK-UCL. DR GO; GO:1904238; P:pericyte cell differentiation; IMP:ARUK-UCL. DR GO; GO:1905036; P:positive regulation of antifungal innate immune response; IMP:ARUK-UCL. DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:1904151; P:positive regulation of microglial cell mediated cytotoxicity; IMP:ARUK-UCL. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:2000529; P:positive regulation of myeloid dendritic cell chemotaxis; IMP:ARUK-UCL. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:ARUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0002572; P:pro-T cell differentiation; IMP:ARUK-UCL. DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IMP:ARUK-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0045646; P:regulation of erythrocyte differentiation; ISO:MGI. DR GO; GO:1905453; P:regulation of myeloid progenitor cell differentiation; IMP:ARUK-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:MGI. DR GO; GO:0036462; P:TRAIL-activated apoptotic signaling pathway; ISO:MGI. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IDA:ARUK-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:ARUK-UCL. DR GO; GO:0001944; P:vasculature development; IMP:MGI. 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; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR11849; ETS; 1. DR PANTHER; PTHR11849:SF16; TRANSCRIPTION FACTOR PU.1; 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; PS00345; ETS_DOMAIN_1; 1. DR PROSITE; PS00346; ETS_DOMAIN_2; 1. DR PROSITE; PS50061; ETS_DOMAIN_3; 1. DR Genevisible; P17433; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; Developmental protein; DNA-binding; Nucleus; KW Phosphoprotein; Proto-oncogene; Reference proteome; RNA-binding; KW Transcription; Transcription regulation. FT CHAIN 1..272 FT /note="Transcription factor PU.1" FT /id="PRO_0000204133" FT DNA_BIND 172..255 FT /note="ETS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00237" FT REGION 126..165 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 132..146 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 219 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /note="forms a salt bridge with the phosphate backbone of FT the opposite strand downstream of the GGAA core sequence" FT /evidence="ECO:0000269|PubMed:8602247" FT BINDING 232 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /note="contacts bases in the GGAA sequence in the major FT groove" FT /evidence="ECO:0000269|PubMed:8602247, FT ECO:0007744|PDB:1PUE" FT BINDING 235 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /note="contacts bases in the GGAA sequence in the major FT groove" FT /evidence="ECO:0000269|PubMed:8602247, FT ECO:0007744|PDB:1PUE" FT BINDING 245 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /note="contacts the phosphate backbone of the GGAA sequence FT in the minor groove upstream" FT /evidence="ECO:0000269|PubMed:8602247" FT MOD_RES 142 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P17947" FT MOD_RES 148 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT HELIX 174..184 FT /evidence="ECO:0007829|PDB:1PUE" FT TURN 188..190 FT /evidence="ECO:0007829|PDB:1PUE" FT STRAND 191..195 FT /evidence="ECO:0007829|PDB:1PUE" FT TURN 196..199 FT /evidence="ECO:0007829|PDB:1PUE" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:1PUE" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:1PUE" FT HELIX 208..219 FT /evidence="ECO:0007829|PDB:1PUE" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:5W3G" FT HELIX 227..240 FT /evidence="ECO:0007829|PDB:1PUE" FT STRAND 241..245 FT /evidence="ECO:0007829|PDB:1PUE" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:1PUE" FT HELIX 256..260 FT /evidence="ECO:0007829|PDB:5W3G" SQ SEQUENCE 272 AA; 31349 MW; 765E9CC2F374EB6E CRC64; MLQACKMEGF SLTAPPSDDL VTYDSELYQR PMHDYYSFVG SDGESHSDHY WDFSAHHVHN NEFENFPENH FTELQSVQPP QLQQLYRHME LEQMHVLDTP MVPPHTGLSH QVSYMPRMCF PYQTLSPAHQ QSSDEEEGER QSPPLEVSDG EADGLEPGPG LLHGETGSKK KIRLYQFLLD LLRSGDMKDS IWWVDKDKGT FQFSSKHKEA LAHRWGIQKG NRKKMTYQKM ARALRNYGKT GEVKKVKKKL TYQFSGEVLG RGGLAERRLP PH //