P28033 · CEBPB_MOUSE
- ProteinCCAAT/enhancer-binding protein beta
- GeneCebpb
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids296 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:16585579, PubMed:17911624, PubMed:18486321, PubMed:20111005).
Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis (PubMed:10635333, PubMed:17301242, PubMed:17601773, PubMed:19478079, PubMed:24061474, PubMed:24216764, PubMed:9727068).
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 roles with CEBPA (PubMed:15509779).
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 (PubMed:10635333, PubMed:16585579, PubMed:9727068).
Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Also plays a role in intracellular bacteria killing (PubMed:17911624).
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:15985551, PubMed:17301242, PubMed:17601773, PubMed:20194620).
Essential for female reproduction because of a critical role in ovarian follicle development (PubMed:9303532).
Restricts osteoclastogenesis (PubMed:19440205).
Together with NFE2L1; represses expression of DSPP during odontoblast differentiation (By similarity).
Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis (PubMed:10635333, PubMed:17301242, PubMed:17601773, PubMed:19478079, PubMed:24061474, PubMed:24216764, PubMed:9727068).
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 roles with CEBPA (PubMed:15509779).
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 (PubMed:10635333, PubMed:16585579, PubMed:9727068).
Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Also plays a role in intracellular bacteria killing (PubMed:17911624).
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:15985551, PubMed:17301242, PubMed:17601773, PubMed:20194620).
Essential for female reproduction because of a critical role in ovarian follicle development (PubMed:9303532).
Restricts osteoclastogenesis (PubMed:19440205).
Together with NFE2L1; represses expression of DSPP during odontoblast differentiation (By similarity).
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.
Isoform 3
Acts as a dominant negative through heterodimerization with isoform 2 (By similarity).
Promotes osteoblast differentiation and osteoclastogenesis (PubMed:19440205).
Promotes osteoblast differentiation and osteoclastogenesis (PubMed:19440205).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCCAAT/enhancer-binding protein beta
- Short namesC/EBP beta
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP28033
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Embryos display defects in brown fat tissue development (PubMed:19641492).
Females are sterile, ovaries lack corpora lutea (PubMed:9303532).
Upon bacterial infection, animals show impaired bactericidal activity and die within 3 days (PubMed:17911624).
Posthepatectomy, animals show a reduced regenerative response with DNA synthesis decreased to 25% of normal in hepatocytes and a prolonged period of hypoglycemia (PubMed:9727068).
Animals show osteopenia with decreased bone formation and enhanced ostecolastogenesis. Long bones have a 1.6 fold diminished bone volume with a reduction of the number and thickness of bone trabeculae (PubMed:19440205).
Mutants of isoform 2 show impaired CSF3/G-CSF production by macrophages, IFNG production by CD4+ T-cells and granuloma formation in liver. Upon bacterial infection, mutants of isoform 2 die within 6 days. Resistant to LPS-induced endotoxin shock (PubMed:17911624).
Double knockout CEBPA and CEBPB results in embryonic developmental arrest and death at around 10 dpc to 11 dpc, associated with a gross placenta failure (PubMed:15509779).
Females are sterile, ovaries lack corpora lutea (PubMed:9303532).
Upon bacterial infection, animals show impaired bactericidal activity and die within 3 days (PubMed:17911624).
Posthepatectomy, animals show a reduced regenerative response with DNA synthesis decreased to 25% of normal in hepatocytes and a prolonged period of hypoglycemia (PubMed:9727068).
Animals show osteopenia with decreased bone formation and enhanced ostecolastogenesis. Long bones have a 1.6 fold diminished bone volume with a reduction of the number and thickness of bone trabeculae (PubMed:19440205).
Mutants of isoform 2 show impaired CSF3/G-CSF production by macrophages, IFNG production by CD4+ T-cells and granuloma formation in liver. Upon bacterial infection, mutants of isoform 2 die within 6 days. Resistant to LPS-induced endotoxin shock (PubMed:17911624).
Double knockout CEBPA and CEBPB results in embryonic developmental arrest and death at around 10 dpc to 11 dpc, associated with a gross placenta failure (PubMed:15509779).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 39 | No effect on interaction with EP300. | ||||
Sequence: K → A or Q | ||||||
Mutagenesis | 39 | Dominant negative. Loss of transactivation activity. No effect on interaction with EP300. | ||||
Sequence: K → R | ||||||
Mutagenesis | 98 | No effect on transactivation activity. Not acetylated after glucocorticoid-stimulation and no increase of transactivation activity; when associated with R-101 and R-102. | ||||
Sequence: K → R | ||||||
Mutagenesis | 101 | Not acetylated after glucocorticoid-stimulation and no increase of transactivation activity; when associated with R-98 and R-102. | ||||
Sequence: K → R | ||||||
Mutagenesis | 102 | Not acetylated and no increase of transactivation activity after glucocorticoid-stimulation; when associated with R-98 and R-101. | ||||
Sequence: K → R | ||||||
Mutagenesis | 133 | Not sumoylated. Decreases ubiquitination and increases stability. Loss of proliferation inhibition in T cells. No effect on transactivation activity. | ||||
Sequence: K → R | ||||||
Mutagenesis | 135 | Not sumoylated and not ubiquitinated. | ||||
Sequence: E → A | ||||||
Mutagenesis | 179 | Disruption of phosphorylation by MAPK and GSK3B, acquisition of DNA-binding activity and transactivation function; when associated with A-184 and A-188. | ||||
Sequence: T → A | ||||||
Mutagenesis | 180 | Highly increases transactivation activity; when associated with A-181. | ||||
Sequence: S → A | ||||||
Mutagenesis | 181 | Highly increases transactivation activity; when associated with A-180. | ||||
Sequence: S → A | ||||||
Mutagenesis | 184 | Disruption of phosphorylation by MAPK and GSK3B, acquisition of DNA-binding activity and transactivation function; when associated with A-179 and A-188. | ||||
Sequence: S → A | ||||||
Mutagenesis | 188 | Disruption of phosphorylation by MAPK and GSK3B, acquisition of DNA-binding activity and transactivation function; when associated with A-179 and A-184. | ||||
Sequence: T → A | ||||||
Mutagenesis | 215 | No effect on transactivation activity. | ||||
Sequence: K → R | ||||||
Mutagenesis | 217 | Loss of hepatocyte proliferation induction by TGFA. | ||||
Sequence: T → A | ||||||
Mutagenesis | 217 | Induces hepatocyte proliferation. | ||||
Sequence: T → E | ||||||
Mutagenesis | 276 | Reduces phosphorylation in response to calcium. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue, cross-link, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000076618 | 1-296 | CCAAT/enhancer-binding protein beta | |||
Sequence: MHRLLAWDAACLPPPPAAFRPMEVANFYYEPDCLAYGAKAARAAPRAPAAEPAIGEHERAIDFSPYLEPLAPAADFAAPAPAHHDFLSDLFADDYGAKPSKKPADYGYVSLGRAGAKAAPPACFPPPPPAALKAEPGFEPADCKRADDAPAMAAGFPFALRAYLGYQATPSGSSGSLSTSSSSSPPGTPSPADAKAAPAACFAGPPAAPAKAKAKKTVDKLSDEYKMRRERNNIAVRKSRDKAKMRNLETQHKVLELTAENERLQKKVEQLSRELSTLRNLFKQLPEPLLASAGHC | ||||||
Modified residue | 3 | Asymmetric dimethylarginine; by CARM1 | ||||
Sequence: R | ||||||
Modified residue | 39 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 39 | N6-methylated lysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 98 | N6-acetyllysine; by KAT2A and KAT2B | ||||
Sequence: K | ||||||
Modified residue | 101 | N6-acetyllysine; by KAT2A and KAT2B | ||||
Sequence: K | ||||||
Modified residue | 102 | N6-acetyllysine; by KAT2A and KAT2B; alternate | ||||
Sequence: K | ||||||
Cross-link | 102 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 133 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 133 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 144 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 179 | Phosphothreonine; by GSK3-beta | ||||
Sequence: T | ||||||
Glycosylation | 180 | O-linked (GlcNAc) serine | ||||
Sequence: S | ||||||
Glycosylation | 181 | O-linked (GlcNAc) serine | ||||
Sequence: S | ||||||
Modified residue | 184 | Phosphoserine; by GSK3-beta | ||||
Sequence: S | ||||||
Modified residue | 188 | Phosphothreonine; by RPS6KA1, CDK2 and MAPK | ||||
Sequence: T | ||||||
Cross-link | 211 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 213 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 217 | Phosphothreonine; by RPS6KA1 and PKC/PRKCA | ||||
Sequence: T | ||||||
Modified residue | 239 | Phosphoserine; by PKC/PRKCA | ||||
Sequence: S | ||||||
Modified residue | 276 | Phosphoserine; by CaMK2 | ||||
Sequence: S | ||||||
Cross-link | 283 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Post-translational modification
Sumoylated by polymeric chains of SUMO2 or SUMO3. Sumoylation at Lys-133 is required for inhibition of T-cells proliferation (PubMed:16585579).
In adipocytes, sumoylation at Lys-133 by PIAS1 leads to ubiquitination and subsequent proteasomal degradation (PubMed:24061474).
Desumoylated by SENP2, which abolishes ubiquitination and stabilizes protein levels (PubMed:20194620).
In adipocytes, sumoylation at Lys-133 by PIAS1 leads to ubiquitination and subsequent proteasomal degradation (PubMed:24061474).
Desumoylated by SENP2, which abolishes ubiquitination and stabilizes protein levels (PubMed:20194620).
Ubiquitinated, leading to proteasomal degradation.
Phosphorylated at Thr-188 by MAPK and CDK2, serves to prime phosphorylation at Thr-179 and Ser-184 by GSK3B and acquire DNA-binding as well as transactivation activities, required to induce adipogenesis. MAPK and CDK2 act sequentially to maintain Thr-188 in the primed phosphorylated state during mitotical cloning expansion and thereby progression of terminal differentiation. Phosphorylation at Thr-217 enhances transactivation activity. Phosphorylation at Ser-276 in response to calcium increases transactivation activity (PubMed:1314426).
Phosphorylated at Thr-188 by RPS6KA1 (By similarity).
Phosphorylated at Thr-188 by RPS6KA1 (By similarity).
O-glycosylated, glycosylation at Ser-180 and Ser-181 prevents phosphorylation on Thr-188, Ser-184 and Thr-179 and DNA binding activity which delays the adipocyte differentiation program.
Acetylated. Acetylation at Lys-39 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 (PubMed:18486321).
Acetylated by KAT2A and KAT2B within a cluster of lysine residues between amino acids 98-102, this acetylation is strongly induced by glucocorticoid treatment and enhances transactivation activity (PubMed:17301242).
Acetylated by KAT2A and KAT2B within a cluster of lysine residues between amino acids 98-102, this acetylation is strongly induced by glucocorticoid treatment and enhances transactivation activity (PubMed:17301242).
Methylated. Methylation at Arg-3 by CARM1 and at Lys-39 by EHMT2, inhibits transactivation activity. Methylation is probably inhibited by phosphorylation at Thr-188.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Abundantly expressed in myoblasts. Enriched in brown adipose tissue (BAT) versus white adipose tissue (WAT). Expressed in hepatocytes (at protein level). Expressed in T lymphocytes (PubMed:16585579).
The expression in granulosa cells of antral follicles is induced by luteinizing hormone (PubMed:9303532).
Expressed in chondrocytes and osteoblasts (at protein level) (PubMed:19440205).
The expression in granulosa cells of antral follicles is induced by luteinizing hormone (PubMed:9303532).
Expressed in chondrocytes and osteoblasts (at protein level) (PubMed:19440205).
Induction
Up-regulated by cold exposure.
Developmental stage
At 9.5 dpc, expressed in the chorionic plate and ectoplacental cone. From 10.5 dpc to at least 11.5 dpc, is also expressed in the trophoblast cells of the three placenta layers (PubMed:15509779).
Expressed in monocytic precursors but is vanished during differentiation into osteoclasts. The expression increases during osteoblast differentiation (PubMed:19440205).
Expressed in monocytic precursors but is vanished during differentiation into osteoclasts. The expression increases during osteoblast differentiation (PubMed:19440205).
Gene expression databases
Interaction
Subunit
Binds DNA as a homodimer and as a heterodimer. 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 CEBPA, CEBPD and CEBPE (By similarity).
Interacts with SIX1 (PubMed:27923061).
Isoform 2 and isoform 3 also form heterodimers (By similarity).
Interacts with TRIM28 and PTGES2 (PubMed:15879117, PubMed:9742105).
Interacts with PRDM16 (PubMed:19641492).
Interacts with CCDC85B (PubMed:15644333).
Forms a complex with THOC5 (PubMed:19015024).
Interacts with ZNF638; this interaction increases transcriptional activation (PubMed:21602272).
Interacts with CIDEA and CIDEC (PubMed:22245780).
Interaction with CIDEA increases transcriptional activation of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH. Interaction with CIDEC increases transcriptional activation of SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. Interacts with DDIT3/CHOP. Interacts with EP300; recruits EP300 to chromatin. Interacts with RORA; the interaction disrupts interaction with EP300 (PubMed:19324970).
Interacts (not methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1 (PubMed:20111005).
Interacts with KAT2A and KAT2B (PubMed:17301242).
Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding (PubMed:24216764).
Interacts with NFE2L1; the heterodimer represses expression of DSPP during odontoblast differentiation (By similarity).
Interacts with MYB; within the complex, MYB and CEBPB bind to different promoter regions (PubMed:11792321).
Can form stable heterodimers with CEBPA, CEBPD and CEBPE (By similarity).
Interacts with SIX1 (PubMed:27923061).
Isoform 2 and isoform 3 also form heterodimers (By similarity).
Interacts with TRIM28 and PTGES2 (PubMed:15879117, PubMed:9742105).
Interacts with PRDM16 (PubMed:19641492).
Interacts with CCDC85B (PubMed:15644333).
Forms a complex with THOC5 (PubMed:19015024).
Interacts with ZNF638; this interaction increases transcriptional activation (PubMed:21602272).
Interacts with CIDEA and CIDEC (PubMed:22245780).
Interaction with CIDEA increases transcriptional activation of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH. Interaction with CIDEC increases transcriptional activation of SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. Interacts with DDIT3/CHOP. Interacts with EP300; recruits EP300 to chromatin. Interacts with RORA; the interaction disrupts interaction with EP300 (PubMed:19324970).
Interacts (not methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1 (PubMed:20111005).
Interacts with KAT2A and KAT2B (PubMed:17301242).
Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding (PubMed:24216764).
Interacts with NFE2L1; the heterodimer represses expression of DSPP during odontoblast differentiation (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P28033 | Bhlhe41 Q99PV5 | 5 | EBI-1029979, EBI-6143801 | |
BINARY | P28033 | Chd8 Q09XV5 | 2 | EBI-1029979, EBI-1169080 | |
BINARY | P28033 | Kat2a Q9JHD2 | 5 | EBI-1029979, EBI-2943116 | |
XENO | P28033 | KAT2B Q92831 | 2 | EBI-1029979, EBI-477430 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-22 | Required for Lys-133 sumoylation | ||||
Sequence: MHRLLAWDAACLPPPPAAFRPM | ||||||
Region | 22-104 | Required for MYC transcriptional repression | ||||
Sequence: MEVANFYYEPDCLAYGAKAARAAPRAPAAEPAIGEHERAIDFSPYLEPLAPAADFAAPAPAHHDFLSDLFADDYGAKPSKKPA | ||||||
Compositional bias | 171-189 | Polar residues | ||||
Sequence: SGSSGSLSTSSSSSPPGTP | ||||||
Region | 171-199 | Disordered | ||||
Sequence: SGSSGSLSTSSSSSPPGTPSPADAKAAPA | ||||||
Domain | 222-285 | bZIP | ||||
Sequence: SDEYKMRRERNNIAVRKSRDKAKMRNLETQHKVLELTAENERLQKKVEQLSRELSTLRNLFKQL | ||||||
Region | 226-246 | Basic motif | ||||
Sequence: KMRRERNNIAVRKSRDKAKMR | ||||||
Region | 248-255 | Leucine-zipper | ||||
Sequence: LETQHKVL |
Sequence similarities
Belongs to the bZIP family. C/EBP subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative initiation.
P28033-1
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.
- Name1
- Synonymsa, C/EBPbeta-FL, LAP*
- Length296
- Mass (Da)31,446
- Last updated1992-08-01 v1
- Checksum827AC4AFC209AE89
P28033-3
- Name2
- Synonymsb, C/EBPbeta-LAP
- NoteMajor isoform.
- Differences from canonical
- 1-21: Missing
P28033-2
- Name3
- Synonymsc, C/EBPbeta-LIP
- Differences from canonical
- 1-151: Missing
Features
Showing features for alternative sequence, compositional bias.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M61007 EMBL· GenBank· DDBJ | AAA37192.1 EMBL· GenBank· DDBJ | mRNA | ||
X62600 EMBL· GenBank· DDBJ | CAA44484.1 EMBL· GenBank· DDBJ | mRNA | ||
S78572 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |