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 27-MAR-2024, entry version 191. 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). RN [9] RP INVOLVEMENT IN IMD108, VARIANT IMD108 HIS-219, AND CHARACTERIZATION OF RP VARIANT IMD108 HIS-219. RX PubMed=31201888; DOI=10.1016/j.jaci.2019.06.003; RA Goeoes H., Fogarty C.L., Sahu B., Plagnol V., Rajamaeki K., Nurmi K., RA Liu X., Einarsdottir E., Jouppila A., Pettersson T., Vihinen H., RA Krjutskov K., Saavalainen P., Jaervinen A., Muurinen M., Greco D., RA Scala G., Curtis J., Nordstroem D., Flaumenhaft R., Vaarala O., RA Kovanen P.E., Keskitalo S., Ranki A., Kere J., Lehto M., Notarangelo L.D., RA Nejentsev S., Eklund K.K., Varjosalo M., Taipale J., Seppaenen M.R.J.; RT "Gain-of-function CEBPE mutation causes noncanonical autoinflammatory RT inflammasomopathy."; RL J. Allergy Clin. Immunol. 144:1364-1376(2019). RN [10] RP VARIANT SGD1 ALA-218. RX PubMed=17244686; DOI=10.1182/blood-2005-05-022004; RA Khanna-Gupta A., Sun H., Zibello T., Lee H.M., Dahl R., Boxer L.A., RA Berliner N.; RT "Growth factor independence-1 (Gfi-1) plays a role in mediating specific RT granule deficiency (SGD) in a patient lacking a gene-inactivating mutation RT in the C/EBPepsilon gene."; RL Blood 109:4181-4190(2007). RN [11] RP VARIANT SGD1 ALA-218. RX PubMed=29651288; DOI=10.3389/fimmu.2018.00588; RA Serwas N.K., Huemer J., Dieckmann R., Mejstrikova E., Garncarz W., RA Litzman J., Hoeger B., Zapletal O., Janda A., Bennett K.L., Kain R., RA Kerjaschky D., Boztug K.; RT "CEBPE-mutant specific granule deficiency correlates with aberrant granule RT organization and substantial proteome alterations in neutrophils."; RL Front. Immunol. 9:588-588(2018). RN [12] RP VARIANT SGD1 135-ARG--SER-281 DEL. RX PubMed=32391290; DOI=10.3389/fped.2020.00117; RA Leszcynska M., Patel B., Morrow M., Chamizo W., Tuite G., Berman D.M., RA Potthast K., Hsu A.P., Holland S.M., Leiding J.W.; RT "Brain Abscess as Severe Presentation of Specific Granule Deficiency."; RL Front. Pediatr. 8:117-117(2020). 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 immunologic disorder characterized by recurrent pyogenic infections, CC defective neutrophil chemotaxis and bactericidal activity, and lack of CC neutrophil secondary granule proteins. Neutrophils of affected CC individuals lack lactoferrin and show abnormal nuclear segmentation, CC bilobed nuclei, low alkaline phosphatase, and increased number of CC neutrophil mitochondria and ribosomes. SGD1 inheritance can be CC autosomal dominant or recessive. {ECO:0000269|PubMed:10359588, CC ECO:0000269|PubMed:11313242, ECO:0000269|PubMed:17244686, CC ECO:0000269|PubMed:26019275, ECO:0000269|PubMed:29651288, CC ECO:0000269|PubMed:32391290}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Immunodeficiency 108 with autoinflammation (IMD108) CC [MIM:260570]: An autosomal recessive disorder characterized by CC autoinflammation and immune impairment of neutrophils, manifesting CC around adolescence. Affected individuals have recurrent episodes of CC abdominal pain associated with fever and elevated inflammatory markers. CC Additional features include recurrent infections, particularly of the CC skin and nails, poor wound healing, and mild bleeding tendencies. CC {ECO:0000269|PubMed:31201888}. 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/"; 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; 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; 57. 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 GlyGen; Q15744; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15744; -. DR PhosphoSitePlus; Q15744; -. DR BioMuta; CEBPE; -. DR DMDM; 62512175; -. DR EPD; Q15744; -. DR MassIVE; Q15744; -. DR MaxQB; Q15744; -. DR PaxDb; 9606-ENSP00000206513; -. DR PeptideAtlas; Q15744; -. DR ProteomicsDB; 60732; -. DR Antibodypedia; 150; 430 antibodies from 31 providers. DR DNASU; 1053; -. DR Ensembl; ENST00000206513.6; ENSP00000206513.5; ENSG00000092067.7. 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 AGR; HGNC:1836; -. 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; 260570; 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; 2959124at2759; -. 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; 41 hits in 1173 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 84 other cell types or tissues. 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:0006351; P:DNA-templated transcription; IEA:InterPro. DR GO; GO:0030851; P:granulocyte differentiation; IMP:UniProtKB. DR GO; GO:0140467; P:integrated stress response signaling; NAS: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 CDD; cd14715; bZIP_CEBPE; 1. DR Gene3D; 1.20.5.170; -; 1. DR IDEAL; IID00618; -. DR InterPro; IPR004827; bZIP. DR InterPro; IPR046347; bZIP_sf. DR InterPro; IPR031106; C/EBP. DR InterPro; IPR016468; C/EBP_chordates. DR PANTHER; PTHR23334; CCAAT/ENHANCER BINDING PROTEIN; 1. DR PANTHER; PTHR23334:SF27; CCAAT_ENHANCER-BINDING PROTEIN EPSILON; 1. DR Pfam; PF07716; bZIP_2; 1. DR PIRSF; PIRSF005879; CCAAT/enhancer-binding; 1. DR SMART; SM00338; BRLZ; 1. DR SUPFAM; SSF57959; Leucine zipper domain; 1. DR PROSITE; PS50217; BZIP; 1. DR Genevisible; Q15744; HS. 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 135..281 FT /note="Missing (in SGD1)" FT /evidence="ECO:0000269|PubMed:32391290" FT /id="VAR_087819" FT VARIANT 218 FT /note="V -> A (in SGD1)" FT /evidence="ECO:0000269|PubMed:17244686, FT ECO:0000269|PubMed:29651288" FT /id="VAR_087820" FT VARIANT 219 FT /note="R -> H (in IMD108; gain-of-function variant FT resulting in increased DNA-binding transcription factor FT activity and decreased association with transcriptional FT repressors)" FT /evidence="ECO:0000269|PubMed:31201888" FT /id="VAR_087821" 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 //