CEBPE_HUMAN
ID CEBPE_HUMAN Reviewed; 281 AA.
AC Q15744; Q15745; Q8IYI2; Q99803;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=CCAAT/enhancer-binding protein epsilon;
DE Short=C/EBP epsilon;
GN Name=CEBPE;
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 [GENOMIC DNA / MRNA].
RX PubMed=8661101; DOI=10.1006/geno.1996.0319;
RA Antonson P., Stellan B., Yamanaka R., Xanthopoulos K.G.;
RT "A novel human CCAAT/enhancer binding protein gene, C/EBPepsilon, is
RT expressed in cells of lymphoid and myeloid lineages and is localized on
RT chromosome 14q11.2 close to the T-cell receptor alpha/delta locus.";
RL Genomics 35:30-38(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND
RP CHARACTERIZATION.
RX PubMed=9032264; DOI=10.1128/mcb.17.3.1375;
RA Chumakov A.M., Grillier I., Chumakova E., Chih D., Slater J.,
RA Koeffler H.P.;
RT "Cloning of the novel human myeloid-cell-specific C/EBP-epsilon
RT transcription factor.";
RL Mol. Cell. Biol. 17:1375-1386(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 INVOLVEMENT IN SGD1.
RX PubMed=10359588; DOI=10.1084/jem.189.11.1847;
RA Lekstrom-Himes J.A., Dorman S.E., Kopar P., Holland S.M., Gallin J.I.;
RT "Neutrophil-specific granule deficiency results from a novel mutation with
RT loss of function of the transcription factor CCAAT/enhancer binding protein
RT epsilon.";
RL J. Exp. Med. 189:1847-1852(1999).
RN [5]
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN SGD1.
RX PubMed=11313242; DOI=10.1182/blood.v97.9.2561;
RA Gombart A.F., Shiohara M., Kwok S.H., Agematsu K., Komiyama A.,
RA Koeffler H.P.;
RT "Neutrophil-specific granule deficiency: homozygous recessive inheritance
RT of a frameshift mutation in the gene encoding transcription factor
RT CCAAT/enhancer binding protein--epsilon.";
RL Blood 97:2561-2567(2001).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH GATA1 AND SPI1,
RP VARIANT SGD1 248-SER-ARG-249 DEL, AND CHARACTERIZATION OF VARIANT SGD1
RP 248-SER-ARG-249 DEL.
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).
RN [7]
RP INTERACTION WITH SMARCD2.
RX PubMed=28369036; DOI=10.1038/ng.3833;
RA Witzel M., Petersheim D., Fan Y., Bahrami E., Racek T., Rohlfs M.,
RA Puchalka J., Mertes C., Gagneur J., Ziegenhain C., Enard W.,
RA Stray-Pedersen A., Arkwright P.D., Abboud M.R., Pazhakh V., Lieschke G.J.,
RA Krawitz P.M., Dahlhoff M., Schneider M.R., Wolf E., Horny H.P., Schmidt H.,
RA Schaeffer A.A., Klein C.;
RT "Chromatin-remodeling factor SMARCD2 regulates transcriptional networks
RT controlling differentiation of neutrophil granulocytes.";
RL Nat. Genet. 49:742-752(2017).
RN [8]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-121, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Transcriptional activator (PubMed:26019275). C/EBP are DNA-
CC binding proteins that recognize two different motifs: the CCAAT
CC homology common to many promoters and the enhanced core homology common
CC to many enhancers. Required for the promyelocyte-myelocyte transition
CC in myeloid differentiation (PubMed:10359588).
CC {ECO:0000269|PubMed:10359588, ECO:0000269|PubMed:26019275}.
CC -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer
CC (PubMed:26019275). Can form stable heterodimers with CEBPA, CEBPB and
CC CEBPD (By similarity). Interacts with GATA1 AND SPI1 (PubMed:26019275).
CC Interacts with SMARCD2 (PubMed:28369036).
CC {ECO:0000250|UniProtKB:P56261, ECO:0000269|PubMed:26019275,
CC ECO:0000269|PubMed:28369036}.
CC -!- INTERACTION:
CC Q15744; P18847: ATF3; NbExp=2; IntAct=EBI-3907048, EBI-712767;
CC Q15744; P18848: ATF4; NbExp=2; IntAct=EBI-3907048, EBI-492498;
CC Q15744; Q16520: BATF; NbExp=2; IntAct=EBI-3907048, EBI-749503;
CC Q15744; Q9NR55: BATF3; NbExp=2; IntAct=EBI-3907048, EBI-10312707;
CC Q15744; P49715: CEBPA; NbExp=2; IntAct=EBI-3907048, EBI-1172054;
CC Q15744; P53567: CEBPG; NbExp=2; IntAct=EBI-3907048, EBI-740209;
CC Q15744; P35638: DDIT3; NbExp=3; IntAct=EBI-3907048, EBI-742651;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11313242,
CC ECO:0000269|PubMed:26019275}.
CC -!- TISSUE SPECIFICITY: Strongest expression occurs in promyelocyte and
CC late-myeloblast-like cell lines. {ECO:0000269|PubMed:9032264}.
CC -!- PTM: Phosphorylated.
CC -!- DISEASE: Specific granule deficiency 1 (SGD1) [MIM:245480]: An
CC autosomal recessive disorder characterized by recurrent pyogenic
CC infections, defective neutrophil chemotaxis and bactericidal activity,
CC and lack of neutrophil secondary granule proteins. Neutrophils of
CC affected individuals lack lactoferrin and show abnormal nuclear
CC segmentation, bilobed nuclei, low alkaline phosphatase, and increased
CC number of neutrophil mitochondria and ribosomes.
CC {ECO:0000269|PubMed:10359588, ECO:0000269|PubMed:11313242,
CC ECO:0000269|PubMed:26019275}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51130.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=CEBPEbase; Note=CEBPE mutation db;
CC URL="http://structure.bmc.lu.se/idbase/CEBPEbase/";
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DR EMBL; U48865; AAC50708.1; -; Genomic_DNA.
DR EMBL; U48866; AAC50709.1; -; mRNA.
DR EMBL; U80982; AAC51130.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BC035797; AAH35797.2; -; mRNA.
DR CCDS; CCDS9589.1; -.
DR RefSeq; NP_001796.2; NM_001805.3.
DR PDB; 3T92; X-ray; 1.50 A; A=37-61.
DR PDBsum; 3T92; -.
DR AlphaFoldDB; Q15744; -.
DR SMR; Q15744; -.
DR BioGRID; 107482; 56.
DR ComplexPortal; CPX-6472; bZIP transcription factor complex, ATF3-CEBPE.
DR ComplexPortal; CPX-6529; bZIP transcription factor complex, ATF4-CEBPE.
DR ComplexPortal; CPX-6589; bZIP transcription factor complex, ATF5-CEBPE.
DR ComplexPortal; CPX-7010; bZIP transcription factor complex, BATF-CEBPE.
DR ComplexPortal; CPX-7067; bZIP transcription factor complex, BATF2-CEBPE.
DR ComplexPortal; CPX-7099; bZIP transcription factor complex, BATF3-CEBPE.
DR ComplexPortal; CPX-912; bZIP transcription factor complex, CEBPE-CEBPE.
DR CORUM; Q15744; -.
DR ELM; Q15744; -.
DR IntAct; Q15744; 32.
DR MINT; Q15744; -.
DR STRING; 9606.ENSP00000206513; -.
DR iPTMnet; Q15744; -.
DR PhosphoSitePlus; Q15744; -.
DR BioMuta; CEBPE; -.
DR DMDM; 62512175; -.
DR EPD; Q15744; -.
DR MassIVE; Q15744; -.
DR MaxQB; Q15744; -.
DR PaxDb; Q15744; -.
DR PeptideAtlas; Q15744; -.
DR PRIDE; Q15744; -.
DR ProteomicsDB; 60732; -.
DR Antibodypedia; 150; 392 antibodies from 31 providers.
DR DNASU; 1053; -.
DR Ensembl; ENST00000206513.6; ENSP00000206513.5; ENSG00000092067.6.
DR GeneID; 1053; -.
DR KEGG; hsa:1053; -.
DR MANE-Select; ENST00000206513.6; ENSP00000206513.5; NM_001805.4; NP_001796.2.
DR UCSC; uc001wiv.3; human.
DR CTD; 1053; -.
DR DisGeNET; 1053; -.
DR GeneCards; CEBPE; -.
DR HGNC; HGNC:1836; CEBPE.
DR HPA; ENSG00000092067; Tissue enriched (bone).
DR MalaCards; CEBPE; -.
DR MIM; 245480; phenotype.
DR MIM; 600749; gene.
DR neXtProt; NX_Q15744; -.
DR OpenTargets; ENSG00000092067; -.
DR Orphanet; 566067; CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome.
DR Orphanet; 169142; Recurrent infection due to specific granule deficiency.
DR PharmGKB; PA26379; -.
DR VEuPathDB; HostDB:ENSG00000092067; -.
DR eggNOG; KOG3119; Eukaryota.
DR GeneTree; ENSGT00940000161681; -.
DR HOGENOM; CLU_043327_0_0_1; -.
DR InParanoid; Q15744; -.
DR OMA; CDHEASI; -.
DR OrthoDB; 1284308at2759; -.
DR PhylomeDB; Q15744; -.
DR TreeFam; TF105008; -.
DR PathwayCommons; Q15744; -.
DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis.
DR SignaLink; Q15744; -.
DR SIGNOR; Q15744; -.
DR BioGRID-ORCS; 1053; 38 hits in 1095 CRISPR screens.
DR GeneWiki; CEBPE; -.
DR GenomeRNAi; 1053; -.
DR Pharos; Q15744; Tbio.
DR PRO; PR:Q15744; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q15744; protein.
DR Bgee; ENSG00000092067; Expressed in bone marrow and 83 other tissues.
DR Genevisible; Q15744; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0030851; P:granulocyte differentiation; IMP:UniProtKB.
DR GO; GO:0140467; P:integrated stress response signaling; IC:ComplexPortal.
DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl.
DR GO; GO:0030099; P:myeloid cell differentiation; IBA:GO_Central.
DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR IDEAL; IID00618; -.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR016468; C/EBP_chordates.
DR Pfam; PF07716; bZIP_2; 1.
DR PIRSF; PIRSF005879; CCAAT/enhancer-binding; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Disease variant; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..281
FT /note="CCAAT/enhancer-binding protein epsilon"
FT /id="PRO_0000076624"
FT DOMAIN 204..267
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..228
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 230..237
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PZD9"
FT CROSSLNK 121
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 248..249
FT /note="Missing (in SGD1; decreased function in positive
FT regulation of DNA-templated transcription; loss of
FT interaction with GATA1; decreased interaction with SPI1; no
FT effect on localization to nucleus; no effect on DNA
FT binding; no effect on dimerization)"
FT /evidence="ECO:0000269|PubMed:26019275"
FT /id="VAR_078996"
FT CONFLICT 64
FT /note="P -> S (in Ref. 2; AAC51130)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="G -> R (in Ref. 1; AAC50708/AAC50709)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="Q -> E (in Ref. 2; AAC51130)"
FT /evidence="ECO:0000305"
FT HELIX 37..47
FT /evidence="ECO:0007829|PDB:3T92"
FT HELIX 50..57
FT /evidence="ECO:0007829|PDB:3T92"
SQ SEQUENCE 281 AA; 30603 MW; B0A1DFA88C04C3D0 CRC64;
MSHGTYYECE PRGGQQPLEF SGGRAGPGEL GDMCEHEASI DLSAYIESGE EQLLSDLFAV
KPAPEARGLK GPGTPAFPHY LPPDPRPFAY PPHTFGPDRK ALGPGIYSSP GSYDPRAVAV
KEEPRGPEGS RAASRGSYNP LQYQVAHCGQ TAMHLPPTLA APGQPLRVLK APLATAAPPC
SPLLKAPSPA GPLHKGKKAV NKDSLEYRLR RERNNIAVRK SRDKAKRRIL ETQQKVLEYM
AENERLRSRV EQLTQELDTL RNLFRQIPEA ANLIKGVGGC S
