CEBPB_BOVIN
ID CEBPB_BOVIN Reviewed; 348 AA.
AC O02755;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=CCAAT/enhancer-binding protein beta;
DE Short=C/EBP beta;
GN Name=CEBPB;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Japanese black;
RX PubMed=9051485; DOI=10.2527/1997.752587x;
RA Yamaoka I., Taniguchi Y., Sasaki Y.;
RT "Nucleotide sequence of bovine C/EBP beta gene.";
RL J. Anim. Sci. 75:587-587(1997).
CC -!- FUNCTION: Important transcription factor regulating the expression of
CC genes involved in immune and inflammatory responses. Also plays a
CC significant role in adipogenesis, as well as in the gluconeogenic
CC pathway, liver regeneration, and hematopoiesis. The consensus
CC recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is
CC governed by protein interactions and post-translational protein
CC modifications. During early embryogenesis, plays essential and
CC redundant roles with CEBPA. Has a promitotic effect on many cell types
CC such as hepatocytes and adipocytes but has an antiproliferative effect
CC on T-cells by repressing MYC expression, facilitating differentiation
CC along the T-helper 2 lineage. Binds to regulatory regions of several
CC acute-phase and cytokines genes and plays a role in the regulation of
CC acute-phase reaction and inflammation. Also plays a role in
CC intracellular bacteria killing. During adipogenesis, is rapidly
CC expressed and, after activation by phosphorylation, induces CEBPA and
CC PPARG, which turn on the series of adipocyte genes that give rise to
CC the adipocyte phenotype. The delayed transactivation of the CEBPA and
CC PPARG genes by CEBPB appears necessary to allow mitotic clonal
CC expansion and thereby progression of terminal differentiation.
CC Essential for female reproduction because of a critical role in ovarian
CC follicle development. Restricts osteoclastogenesis: together with
CC NFE2L1; represses expression of DSPP during odontoblast differentiation
CC (By similarity). {ECO:0000250|UniProtKB:P17676,
CC ECO:0000250|UniProtKB:P21272, ECO:0000250|UniProtKB:P28033}.
CC -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer. Interacts with
CC ATF4. Binds DNA as a heterodimer with ATF4. Interacts with MYB; within
CC the complex, MYB and CEBPB bind to different promoter regions. Can form
CC stable heterodimers with CEBPA, CEBPD and CEBPG. Interacts with SIX1
CC (By similarity). Interacts with TRIM28 and PTGES2. Interacts with
CC PRDM16. Interacts with CCDC85B. Forms a complex with THOC5. Interacts
CC with ZNF638; this interaction increases transcriptional activation.
CC Interacts with CIDEA and CIDEC; these interactions increase
CC transcriptional activation of a subset of CEBPB downstream target
CC genes. Interacts with DDIT3/CHOP.Interacts with EP300; recruits EP300
CC to chromatin. Interacts with RORA; the interaction disrupts interaction
CC with EP300. Interacts (not methylated) with MED23, MED26, SMARCA2,
CC SMARCB1 and SMARCC1. Interacts with KAT2A and KAT2B (By similarity).
CC Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction
CC and DNA binding (By similarity). Interacts with NFE2L1; the heterodimer
CC represses expression of DSPP during odontoblast differentiation (By
CC similarity). {ECO:0000250|UniProtKB:P17676,
CC ECO:0000250|UniProtKB:P21272, ECO:0000250|UniProtKB:P28033}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P17676}. Cytoplasm
CC {ECO:0000250|UniProtKB:P17676}. Note=Translocates to the nucleus when
CC phosphorylated at Ser-288. In T-cells when sumoylated drawn to
CC pericentric heterochromatin thereby allowing proliferation (By
CC similarity). {ECO:0000250|UniProtKB:P17676,
CC ECO:0000250|UniProtKB:P28033}.
CC -!- PTM: Methylated. Methylation at Arg-3 by CARM1 and at Lys-43 by EHMT2
CC inhibit transactivation activity. Methylation is probably inhibited by
CC phosphorylation at Thr-236. {ECO:0000250|UniProtKB:P17676}.
CC -!- PTM: Sumoylated by polymeric chains of SUMO2 or SUMO3 (By similarity).
CC Sumoylation at Lys-174 is required for inhibition of T-cells
CC proliferation. In adipocytes, sumoylation at Lys-174 by PIAS1 leads to
CC ubiquitination and subsequent proteasomal degradation. Desumoylated by
CC SENP2, which abolishes ubiquitination and stabilizes protein levels (By
CC similarity). {ECO:0000250|UniProtKB:P17676,
CC ECO:0000250|UniProtKB:P28033}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:P28033}.
CC -!- PTM: Phosphorylated at Thr-236 by MAPK and CDK2, serves to prime
CC phosphorylation at Thr-227 and Ser-232 by GSK3B and acquire DNA-binding
CC as well as transactivation activities, required to induce adipogenesis.
CC MAPK and CDK2 act sequentially to maintain Thr-236 in the primed
CC phosphorylated state during mitotical cloning expansion and thereby
CC progression of terminal differentiation. Phosphorylation at Thr-269
CC enhances transactivation activity. Phosphorylation at Ser-328 in
CC response to calcium increases transactivation activity. Phosphorylated
CC at Thr-236 by RPS6KA1. {ECO:0000250|UniProtKB:P17676,
CC ECO:0000250|UniProtKB:P28033}.
CC -!- PTM: O-glycosylated, glycosylation at Ser-228 and Ser-229 prevents
CC phosphorylation on Thr-236, Ser-232 and Thr-227 and DNA binding
CC activity which delays the adipocyte differentiation program.
CC {ECO:0000250|UniProtKB:P28033}.
CC -!- PTM: Acetylated. Acetylation at Lys-43 is an important and dynamic
CC regulatory event that contributes to its ability to transactivate
CC target genes, including those associated with adipogenesis and
CC adipocyte function. Deacetylation by HDAC1 represses its
CC transactivation activity. Acetylated by KAT2A and KAT2B within a
CC cluster of lysine residues between amino acids 129-133, this
CC acetylation is strongly induced by glucocorticoid treatment and
CC enhances transactivation activity. {ECO:0000250|UniProtKB:P28033}.
CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}.
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DR EMBL; D82985; BAA20096.1; -; Genomic_DNA.
DR RefSeq; NP_789745.1; NM_176788.1.
DR AlphaFoldDB; O02755; -.
DR SMR; O02755; -.
DR PRIDE; O02755; -.
DR GeneID; 338319; -.
DR KEGG; bta:338319; -.
DR CTD; 1051; -.
DR InParanoid; O02755; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0072574; P:hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; ISS:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:1901329; P:regulation of odontoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
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 3: Inferred from homology;
KW Acetylation; Activator; Cytoplasm; Differentiation; DNA-binding;
KW Glycoprotein; Isopeptide bond; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..348
FT /note="CCAAT/enhancer-binding protein beta"
FT /id="PRO_0000076616"
FT DOMAIN 274..337
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..24
FT /note="Required for Lys-174 sumoylation"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT REGION 24..135
FT /note="Required for MYC transcriptional repression"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT REGION 44..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 158..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..298
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 300..307
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 116..124
FT /note="9aaTAD"
FT COMPBIAS 158..175
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..238
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3
FT /note="Asymmetric dimethylarginine; by CARM1"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT MOD_RES 43
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 43
FT /note="N6-methylated lysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 129
FT /note="N6-acetyllysine; by KAT2A and KAT2B"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 132
FT /note="N6-acetyllysine; by KAT2A and KAT2B"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 133
FT /note="N6-acetyllysine; by KAT2A and KAT2B; alternate"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 227
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 232
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 236
FT /note="Phosphothreonine; by RPS6KA1, CDK2 and MAPK"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT MOD_RES 269
FT /note="Phosphothreonine; by RPS6KA1 and PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT MOD_RES 291
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT MOD_RES 328
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT CARBOHYD 228
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT CARBOHYD 229
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:P28033"
FT CROSSLNK 133
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:P17676,
FT ECO:0000250|UniProtKB:P28033"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 185
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 187
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 263
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 265
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
FT CROSSLNK 335
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P17676"
SQ SEQUENCE 348 AA; 36390 MW; 7059D2F87B474CB4 CRC64;
MQRLVVWDPV CLPLPPPPPA FKSMEVANFY YEADCLAAAY GGKAAPAAPP ADRPGPRPPT
GELGSIGEHE RAIDFSPYLE PLGAPQAPAP TTASDTFEAA PSAPAPVPAS SGQHHDFLSD
LFSDDYGGKN CKKAAEYGYV SLGRLGAAKG ALHPGCFAPL HPPPPPPPPP AELKAEPGFE
PADCKRKEEA GAPGGGAAGM AAGFPYALRA YLGYQAVPSG SSGSLSTSSS SSPPGTPSPA
DAKATPAAAA CYAGAAPAPS QVKSKAKKTV DKHSDEYKIR RERNNIAVRK SRDKAKMRNL
ETQHKVLELT GENERLQKKV EQLSREVSTL RNLFKTLPEP LLASSGHC
