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Protein

CCAAT/enhancer-binding protein beta

Gene

CEBPB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:1741402, PubMed:9374525, PubMed:12048245, PubMed:18647749). Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage. Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Plays also a role in intracellular bacteria killing (By similarity). During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation (PubMed:20829347). Essential for female reproduction because of a critical role in ovarian follicle development (By similarity). Restricts osteoclastogenesis (By similarity).1 PublicationBy similarity4 Publications
Isoform 2: Essential for gene expression induction in activated macrophages. Plays a major role in immune responses such as CD4+ T-cell response, granuloma formation and endotoxin shock. Not essential for intracellular bacteria killing.By similarity
Isoform 3: Acts as a dominant negative through heterodimerization with isoform 2 (PubMed:11741938). Promotes osteoblast differentiation and osteoclastogenesis (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processDifferentiation, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
SignaLinkiP17676.
SIGNORiP17676.

Names & Taxonomyi

Protein namesi
Recommended name:
CCAAT/enhancer-binding protein betaImported
Short name:
C/EBP betaImported
Alternative name(s):
Liver activator protein
Short name:
LAP
Liver-enriched inhibitory protein
Short name:
LIP
Nuclear factor NF-IL61 Publication
Transcription factor 5
Short name:
TCF-5
Gene namesi
Name:CEBPBImported
Synonyms:TCF5
ORF Names:PP9092
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000172216.5.
HGNCiHGNC:1834. CEBPB.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi235T → S: Loss of transactivation activity in response to IFNG. 1 Publication1
Mutagenesisi288S → A: Loss of nuclear translocation. 1 Publication1

Organism-specific databases

DisGeNETi1051.
OpenTargetsiENSG00000172216.
PharmGKBiPA26377.

Polymorphism and mutation databases

BioMutaiCEBPB.
DMDMi34223718.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766171 – 345CCAAT/enhancer-binding protein betaAdd BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3Omega-N-methylated arginine; by CARM11 Publication1
Modified residuei43N6-acetyllysineBy similarity1
Modified residuei129N6-acetyllysine; by KAT2A and KAT2BBy similarity1
Modified residuei132N6-acetyllysine; by KAT2A and KAT2BBy similarity1
Modified residuei133N6-acetyllysine; by KAT2A and KAT2B; alternateBy similarity1
Cross-linki133Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki174Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki174Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki185Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki187Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei226Phosphothreonine; by GSK3-betaBy similarity1
Glycosylationi227O-linked (GlcNAc) serineBy similarity1
Glycosylationi228O-linked (GlcNAc) serineBy similarity1
Modified residuei231Phosphoserine; by GSK3-betaBy similarity1
Modified residuei235Phosphothreonine; by RPS6KA1, CDK2 and MAPK2 Publications1
Cross-linki260Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki262Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei266Phosphothreonine; by RPS6KA1 and PKC/PRKCABy similarity1
Modified residuei288Phosphoserine; by PKC/PRKCA1 Publication1
Modified residuei325Phosphoserine; by CaMK2By similarity1
Cross-linki332Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Methylated. Methylation at Arg-3 by CARM1 and at Lys-43 by EHMT2 inhibit transactivation activity. Methylation is probably inhibited by phosphorylation at Thr-235.2 Publications
Sumoylated by polymeric chains of SUMO2 or SUMO3 (PubMed:12810706). Sumoylation at Lys-174 is required for inhibition of T-cells proliferation. In adipocytes, sumoylation at Lys-174 by PIAS1 leads to ubiquitination and subsequent proteasomal degradation. Desumoylated by SENP2, which abolishes ubiquitination and stabilizes protein levels (By similarity).By similarity1 Publication
Ubiquitinated, leading to proteasomal degradation.By similarity
Phosphorylated at Thr-235 by MAPK and CDK2, serves to prime phosphorylation at Thr-226 and Ser-231 by GSK3B and acquire DNA-binding as well as transactivation activities, required to induce adipogenesis. MAPK and CDK2 act sequentially to maintain Thr-235 in the primed phosphorylated state during mitotical cloning expansion and thereby progression of terminal differentiation. Phosphorylation at Thr-266 enhances transactivation activity. Phosphorylation at Ser-325 in response to calcium increases transactivation activity. Phosphorylated at Thr-235 by RPS6KA1 (PubMed:11684016).By similarity1 Publication
O-glycosylated, glycosylation at Ser-227 and Ser-228 prevents phosphorylation on Thr-235, Ser-231 and Thr-226 and DNA binding activity which delays the adipocyte differentiation program.By similarity
Acetylated. Acetylation at Lys-43 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function. Deacetylation by HDAC1 represses its transactivation activity. Acetylated by KAT2A and KAT2B within a cluster of lysine residues between amino acids 129-133, this acetylation is strongly induced by glucocorticoid treatment and enhances transactivation activity.By similarity

Keywords - PTMi

Acetylation, Glycoprotein, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP17676.
MaxQBiP17676.
PaxDbiP17676.
PeptideAtlasiP17676.
PRIDEiP17676.

PTM databases

iPTMnetiP17676.
PhosphoSitePlusiP17676.

Expressioni

Tissue specificityi

Expressed at low levels in the lung, kidney and spleen.

Inductioni

By ER stress.1 Publication

Gene expression databases

BgeeiENSG00000172216.
CleanExiHS_CEBPB.
GenevisibleiP17676. HS.

Organism-specific databases

HPAiCAB004213.
HPA061355.
HPA062267.

Interactioni

Subunit structurei

Binds DNA as a homodimer and as a heterodimer (PubMed:11018027, PubMed:11257229, PubMed:11792321). Interacts with ATF4. Binds DNA as a heterodimer with ATF4 (PubMed:11018027). Interacts with MYB; within the complex, MYB and CEBPB bind to different promoter regions (PubMed:11792321). Can form stable heterodimers with CEBPD (PubMed:1741402). Can form stable heterodimers with CEBPA and CEBPE (By similarity). Isoform 2 and isoform 3 also form heterodimers. Interacts with TRIM28 and PTGES2. Interacts with PRDM16. Interacts with CCDC85B. Forms a complex with THOC5. Interacts with ZNF638; this interaction increases transcriptional activation. Interacts with CIDEA and CIDEC; these interactions increase transcriptional activation of a subset of CEBPB downstream target genes (By similarity). Interacts with DDIT3/CHOP (PubMed:20829347). Interacts with EP300; recruits EP300 to chromatin. Interacts with RORA; the interaction disrupts interaction with EP300. Interacts (not methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1 (PubMed:20111005). Interacts with KAT2A and KAT2B (By similarity). Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding (By similarity).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107480. 67 interactors.
CORUMiP17676.
DIPiDIP-35345N.
ELMiP17676.
IntActiP17676. 25 interactors.
MINTiMINT-230873.
STRINGi9606.ENSP00000305422.

Structurei

Secondary structure

1345
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi269 – 271Combined sources3
Helixi272 – 328Combined sources57
Turni329 – 331Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GTWX-ray1.85A/B259-336[»]
1GU4X-ray1.80A/B259-336[»]
1GU5X-ray2.10A/B259-336[»]
1H88X-ray2.80A/B259-336[»]
1H89X-ray2.45A/B273-336[»]
1H8AX-ray2.23A/B259-336[»]
1HJBX-ray3.00A/B/D/E259-345[»]
1IO4X-ray3.00A/B259-336[»]
2E42X-ray1.80A/B259-336[»]
2E43X-ray2.10A/B259-336[»]
ProteinModelPortaliP17676.
SMRiP17676.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17676.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini271 – 334bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 24Required for Lys-174 sumoylationAdd BLAST24
Regioni24 – 135Required for MYC transcriptional repressionBy similarityAdd BLAST112
Regioni275 – 295Basic motifPROSITE-ProRule annotationAdd BLAST21
Regioni297 – 304Leucine-zipperPROSITE-ProRule annotation8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi116 – 1249aaTAD9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi162 – 170Poly-Pro9

Domaini

the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.1 Publication

Sequence similaritiesi

Belongs to the bZIP family. C/EBP subfamily.Curated

Phylogenomic databases

eggNOGiENOG410ISXW. Eukaryota.
ENOG410XX4P. LUCA.
GeneTreeiENSGT00530000063192.
HOGENOMiHOG000013112.
HOVERGENiHBG050879.
InParanoidiP17676.
KOiK10048.
OMAiCKKPAEY.
OrthoDBiEOG091G11FC.
PhylomeDBiP17676.
TreeFamiTF105008.

Family and domain databases

InterProiView protein in InterPro
IPR004827. bZIP.
IPR016468. C/EBP_chordates.
PfamiView protein in Pfam
PF07716. bZIP_2. 1 hit.
PIRSFiPIRSF005879. CCAAT/enhancer-binding. 1 hit.
SMARTiView protein in SMART
SM00338. BRLZ. 1 hit.
PROSITEiView protein in PROSITE
PS50217. BZIP. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P17676-1) [UniParc]FASTAAdd to basket
Also known as: C/EBPbeta-FL

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQRLVAWDPA CLPLPPPPPA FKSMEVANFY YEADCLAAAY GGKAAPAAPP
60 70 80 90 100
AARPGPRPPA GELGSIGDHE RAIDFSPYLE PLGAPQAPAP ATATDTFEAA
110 120 130 140 150
PPAPAPAPAS SGQHHDFLSD LFSDDYGGKN CKKPAEYGYV SLGRLGAAKG
160 170 180 190 200
ALHPGCFAPL HPPPPPPPPP AELKAEPGFE PADCKRKEEA GAPGGGAGMA
210 220 230 240 250
AGFPYALRAY LGYQAVPSGS SGSLSTSSSS SPPGTPSPAD AKAPPTACYA
260 270 280 290 300
GAAPAPSQVK SKAKKTVDKH SDEYKIRRER NNIAVRKSRD KAKMRNLETQ
310 320 330 340
HKVLELTAEN ERLQKKVEQL SRELSTLRNL FKQLPEPLLA SSGHC
Length:345
Mass (Da):36,106
Last modified:August 22, 2003 - v2
Checksum:i9B725BD6CCAA771D
GO
Isoform 2 (identifier: P17676-2) [UniParc]FASTAAdd to basket
Also known as: C/EBPbeta-LAP

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Show »
Length:322
Mass (Da):33,592
Checksum:i842B381C36DFA8CE
GO
Isoform 3 (identifier: P17676-3) [UniParc]FASTAAdd to basket
Also known as: C/EBPbeta-LIP

The sequence of this isoform differs from the canonical sequence as follows:
     1-198: Missing.

Show »
Length:147
Mass (Da):15,938
Checksum:i3D75D9D752E47B88
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241A → P no nucleotide entry (PubMed:7635140).Curated1
Sequence conflicti253A → G in CAA36794 (PubMed:2112087).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016300195G → S1 PublicationCorresponds to variant dbSNP:rs4253440Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0533131 – 198Missing in isoform 3. CuratedAdd BLAST198
Alternative sequenceiVSP_0533141 – 23Missing in isoform 2. CuratedAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52560 Genomic DNA. Translation: CAA36794.1.
AF289608 mRNA. Translation: AAL55792.1.
AY193834 Genomic DNA. Translation: AAN86350.1.
AK291536 mRNA. Translation: BAF84225.1.
AL161937 Genomic DNA. Translation: CAC14276.1.
CH471077 Genomic DNA. Translation: EAW75629.1.
BC007538 mRNA. Translation: AAH07538.1.
BC021931 mRNA. Translation: AAH21931.1.
CCDSiCCDS13429.1. [P17676-1]
PIRiS12788.
S66246.
RefSeqiNP_001272807.1. NM_001285878.1. [P17676-2]
NP_001272808.1. NM_001285879.1. [P17676-3]
NP_005185.2. NM_005194.3. [P17676-1]
UniGeneiHs.517106.
Hs.719041.
Hs.720603.

Genome annotation databases

EnsembliENST00000303004; ENSP00000305422; ENSG00000172216. [P17676-1]
GeneIDi1051.
KEGGihsa:1051.
UCSCiuc002xvi.4. human. [P17676-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCEBPB_HUMAN
AccessioniPrimary (citable) accession number: P17676
Secondary accession number(s): A8K671, Q96IH2, Q9H4Z5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 22, 2003
Last modified: October 25, 2017
This is version 194 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families