SPI1_HUMAN
ID SPI1_HUMAN Reviewed; 270 AA.
AC P17947;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Transcription factor PU.1;
DE AltName: Full=31 kDa-transforming protein;
GN Name=SPI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1693183;
RA Ray D., Culine S., Tavitian A., Moreau-Gachelin F.;
RT "The human homologue of the putative proto-oncogene Spi-1: characterization
RT and expression in tumors.";
RL Oncogene 5:663-668(1990).
RN [2]
RP ERRATUM OF PUBMED:1693183, AND SEQUENCE REVISION.
RA Ray D., Culine S., Tavitian A., Moreau-Gachelin F.;
RL Oncogene 5:1611-1612(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal liver;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP INTERACTION WITH SPIB.
RX PubMed=10196196; DOI=10.1074/jbc.274.16.11115;
RA Rao S., Matsumura A., Yoon J., Simon M.C.;
RT "SPI-B activates transcription via a unique proline, serine, and threonine
RT domain and exhibits DNA binding affinity differences from PU.1.";
RL J. Biol. Chem. 274:11115-11124(1999).
RN [6]
RP INTERACTION WITH RUNX1.
RX PubMed=10207087; DOI=10.1128/mcb.19.5.3635;
RA Mao S., Frank R.C., Zhang J., Miyazaki Y., Nimer S.D.;
RT "Functional and physical interactions between AML1 proteins and an ETS
RT protein, MEF: implications for the pathogenesis of t(8;21)-positive
RT leukemias.";
RL Mol. Cell. Biol. 19:3635-3644(1999).
RN [7]
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 [8]
RP INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23166356; DOI=10.1084/jem.20121387;
RA Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C.,
RA Dalla-Favera R.;
RT "BCL6 positively regulates AID and germinal center gene expression via
RT repression of miR-155.";
RL J. Exp. Med. 209:2455-2465(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140 AND SER-146, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP INTERACTION WITH CEBPE.
RX PubMed=26019275; DOI=10.4049/jimmunol.1402222;
RA Wada T., Akagi T., Muraoka M., Toma T., Kaji K., Agematsu K.,
RA Koeffler H.P., Yokota T., Yachie A.;
RT "A novel in-frame deletion in the leucine zipper domain of C/EBPepsilon
RT leads to neutrophil-specific granule deficiency.";
RL J. Immunol. 195:80-86(2015).
CC -!- FUNCTION: Binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA-
CC 3') that can act as a lymphoid-specific enhancer. This protein is a
CC transcriptional activator that may be specifically involved in the
CC differentiation or activation of macrophages or B-cells. Also binds RNA
CC and may modulate pre-mRNA splicing (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds DNA as a monomer. Interacts with CEBPD and NONO (By
CC similarity). Interacts with RUNX1 and SPIB. Interacts with GFI1; the
CC interaction represses SPI1 transcriptional activity. Interacts with
CC CEBPE (PubMed:26019275). {ECO:0000250, ECO:0000269|PubMed:10196196,
CC ECO:0000269|PubMed:10207087, ECO:0000269|PubMed:17197705,
CC ECO:0000269|PubMed:26019275}.
CC -!- INTERACTION:
CC P17947; P23769: GATA2; NbExp=4; IntAct=EBI-2293548, EBI-2806671;
CC P17947; P31260: HOXA10; NbExp=2; IntAct=EBI-2293548, EBI-2293516;
CC P17947; Q15156: PML-RAR; NbExp=20; IntAct=EBI-2293548, EBI-867256;
CC P17947; P78527: PRKDC; NbExp=2; IntAct=EBI-2293548, EBI-352053;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00237,
CC ECO:0000269|PubMed:23166356}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P17947-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P17947-2; Sequence=VSP_038690;
CC -!- INDUCTION: Highly expressed in both FV-P and FV-A-induced erythro-
CC leukemia cell lines that have undergone rearrangements of the SPI1 gene
CC due to the insertion of SFFV. Negatively regulated by microRNA-155
CC (miR-155). {ECO:0000269|PubMed:23166356}.
CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA36281.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SPI1ID269.html";
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DR EMBL; X52056; CAA36281.1; ALT_INIT; mRNA.
DR EMBL; AL532058; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC090559; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44591.1; -. [P17947-2]
DR CCDS; CCDS7933.2; -. [P17947-1]
DR PIR; S60367; S60367.
DR RefSeq; NP_001074016.1; NM_001080547.1. [P17947-2]
DR RefSeq; NP_003111.2; NM_003120.2. [P17947-1]
DR AlphaFoldDB; P17947; -.
DR SMR; P17947; -.
DR BioGRID; 112566; 46.
DR CORUM; P17947; -.
DR DIP; DIP-953N; -.
DR IntAct; P17947; 13.
DR MINT; P17947; -.
DR STRING; 9606.ENSP00000227163; -.
DR iPTMnet; P17947; -.
DR PhosphoSitePlus; P17947; -.
DR BioMuta; SPI1; -.
DR DMDM; 60415923; -.
DR EPD; P17947; -.
DR MassIVE; P17947; -.
DR PaxDb; P17947; -.
DR PeptideAtlas; P17947; -.
DR PRIDE; P17947; -.
DR ProteomicsDB; 53528; -. [P17947-1]
DR ProteomicsDB; 53529; -. [P17947-2]
DR Antibodypedia; 26734; 556 antibodies from 44 providers.
DR DNASU; 6688; -.
DR Ensembl; ENST00000227163.8; ENSP00000227163.4; ENSG00000066336.12. [P17947-2]
DR Ensembl; ENST00000378538.8; ENSP00000367799.4; ENSG00000066336.12. [P17947-1]
DR GeneID; 6688; -.
DR KEGG; hsa:6688; -.
DR MANE-Select; ENST00000378538.8; ENSP00000367799.4; NM_003120.3; NP_003111.2.
DR UCSC; uc001nfb.2; human. [P17947-1]
DR CTD; 6688; -.
DR DisGeNET; 6688; -.
DR GeneCards; SPI1; -.
DR HGNC; HGNC:11241; SPI1.
DR HPA; ENSG00000066336; Group enriched (bone marrow, lung, lymphoid tissue).
DR MIM; 165170; gene.
DR neXtProt; NX_P17947; -.
DR NIAGADS; ENSG00000066336; -.
DR OpenTargets; ENSG00000066336; -.
DR PharmGKB; PA36071; -.
DR VEuPathDB; HostDB:ENSG00000066336; -.
DR eggNOG; KOG3805; Eukaryota.
DR GeneTree; ENSGT00940000159754; -.
DR HOGENOM; CLU_066451_0_0_1; -.
DR InParanoid; P17947; -.
DR OMA; SYLPRMY; -.
DR OrthoDB; 1272250at2759; -.
DR PhylomeDB; P17947; -.
DR TreeFam; TF352494; -.
DR PathwayCommons; P17947; -.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis.
DR SignaLink; P17947; -.
DR SIGNOR; P17947; -.
DR BioGRID-ORCS; 6688; 69 hits in 1108 CRISPR screens.
DR ChiTaRS; SPI1; human.
DR GeneWiki; SPI1; -.
DR GenomeRNAi; 6688; -.
DR Pharos; P17947; Tbio.
DR PRO; PR:P17947; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P17947; protein.
DR Bgee; ENSG00000066336; Expressed in granulocyte and 101 other tissues.
DR ExpressionAtlas; P17947; baseline and differential.
DR Genevisible; P17947; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005667; C:transcription regulator complex; IDA:ARUK-UCL.
DR GO; GO:0003682; F:chromatin binding; ISS:ARUK-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IDA:ARUK-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS: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; IDA:ARUK-UCL.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; ISS:ARUK-UCL.
DR GO; GO:0051525; F:NFAT protein binding; ISS:BHF-UCL.
DR GO; GO:0140311; F:protein sequestering activity; ISS: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:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0097677; F:STAT family protein binding; IPI:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ARUK-UCL.
DR GO; GO:0060033; P:anatomical structure regression; IEA:Ensembl.
DR GO; GO:1902262; P:apoptotic process involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0002357; P:defense response to tumor cell; IMP:ARUK-UCL.
DR GO; GO:0098508; P:endothelial to hematopoietic transition; ISS:ARUK-UCL.
DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0002316; P:follicular B cell differentiation; IEA:Ensembl.
DR GO; GO:0002314; P:germinal center B cell differentiation; IEA:Ensembl.
DR GO; GO:0030851; P:granulocyte differentiation; IEA:Ensembl.
DR GO; GO:0043966; P:histone H3 acetylation; IMP:UniProtKB.
DR GO; GO:0044027; P:hypermethylation of CpG island; IDA:UniProtKB.
DR GO; GO:0002327; P:immature B cell differentiation; IEA:Ensembl.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IEA:Ensembl.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; IMP:ARUK-UCL.
DR GO; GO:1904178; P:negative regulation of adipose tissue development; ISS:ARUK-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IDA:UniProtKB.
DR GO; GO:0090241; P:negative regulation of histone H4 acetylation; IMP:UniProtKB.
DR GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; IEA:Ensembl.
DR GO; GO:0043314; P:negative regulation of neutrophil degranulation; ISS:ARUK-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:ARUK-UCL.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IMP:ARUK-UCL.
DR GO; GO:0120186; P:negative regulation of protein localization to chromatin; ISS:ARUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:ARUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0090402; P:oncogene-induced cell senescence; ISS:ARUK-UCL.
DR GO; GO:1904238; P:pericyte cell differentiation; ISS:ARUK-UCL.
DR GO; GO:1905036; P:positive regulation of antifungal innate immune response; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1904151; P:positive regulation of microglial cell mediated cytotoxicity; ISS: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; IEA:Ensembl.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0002572; P:pro-T cell differentiation; ISS:ARUK-UCL.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISS:ARUK-UCL.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; IMP:BHF-UCL.
DR GO; GO:1901674; P:regulation of histone H3-K27 acetylation; ISS:ARUK-UCL.
DR GO; GO:1905453; P:regulation of myeloid progenitor cell differentiation; ISS:ARUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:ARUK-UCL.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0036462; P:TRAIL-activated apoptotic signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR DisProt; DP02918; -.
DR Gene3D; 1.10.10.10; -; 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; PTHR11849; 1.
DR Pfam; PF00178; Ets; 1.
DR PRINTS; PR00454; ETSDOMAIN.
DR SMART; SM00413; ETS; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00345; ETS_DOMAIN_1; 1.
DR PROSITE; PS00346; ETS_DOMAIN_2; 1.
DR PROSITE; PS50061; ETS_DOMAIN_3; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; DNA-binding; Nucleus; Phosphoprotein;
KW Proto-oncogene; Reference proteome; RNA-binding; Transcription;
KW Transcription regulation.
FT CHAIN 1..270
FT /note="Transcription factor PU.1"
FT /id="PRO_0000204132"
FT DNA_BIND 170..253
FT /note="ETS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00237"
FT REGION 123..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 15
FT /note="P -> PQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_038690"
SQ SEQUENCE 270 AA; 31083 MW; 9592DAA1D85053ED CRC64;
MLQACKMEGF PLVPPPSEDL VPYDTDLYQR QTHEYYPYLS SDGESHSDHY WDFHPHHVHS
EFESFAENNF TELQSVQPPQ LQQLYRHMEL EQMHVLDTPM VPPHPSLGHQ VSYLPRMCLQ
YPSLSPAQPS SDEEEGERQS PPLEVSDGEA DGLEPGPGLL PGETGSKKKI RLYQFLLDLL
RSGDMKDSIW WVDKDKGTFQ FSSKHKEALA HRWGIQKGNR KKMTYQKMAR ALRNYGKTGE
VKKVKKKLTY QFSGEVLGRG GLAERRHPPH
