UniProt:P28033 Cebpb

chain
  • chain:1-296
checksum 827AC4AFC209AE89
comment
  • 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).FUNCTION 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.FUNCTION Acts as a dominant negative through heterodimerization with isoform 2 (By similarity). Promotes osteoblast differentiation and osteoclastogenesis (PubMed:19440205).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).INTERACTION In T-cells when sumoylated drawn to pericentric heterochromatin thereby allowing proliferation (PubMed:16585579). Translocates to the nucleus when phosphorylated at Ser-288 (By similarity).ALTERNATIVE PRODUCTS 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).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).INDUCTION Up-regulated by cold exposure.PTM 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).PTM Ubiquitinated, leading to proteasomal degradation.PTM 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).PTM 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.PTM 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).PTM 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.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).MISCELLANEOUS Major isoform.SIMILARITY Belongs to the bZIP family. C/EBP subfamily.
crossReference
databaseName UniProt
dbId 87080
description
  • recommendedName: fullName evidence="38"CCAAT/enhancer-binding protein beta shortName: C/EBP beta alternativeName: AGP/EBP alternativeName: Interleukin-6-dependent-binding protein shortName: IL-6DBP alternativeName: Liver-enriched transcriptional activator shortName: LAP
displayName UniProt:P28033 Cebpb
geneName
  • Cebpb
identifier P28033
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Activator
  • Alternative initiation
  • Cytoplasm
  • Differentiation
  • DNA-binding
  • Glycoprotein
  • Isopeptide bond
  • Methylation
  • Nucleus
  • Phosphoprotein
  • Reference proteome
  • Transcription
  • Transcription regulation
  • Ubl conjugation
modified [InstanceEdit:9917590] Weiser, Joel, 2024-08-09
moleculeType Protein
name
  • Cebpb
otherIdentifier
  • 10478890
  • 12608
  • 1418901_at
  • 1427844_a_at
  • 17379938
  • 4547126
  • 4550741
  • 4873135
  • 4898363
  • 5086416
  • 5179157
  • 92925_at
  • A_52_P605846
  • A_55_P2165869
  • GE35206
  • GO:0000122
  • GO:0000779
  • GO:0000785
  • GO:0000976
  • GO:0000977
  • GO:0000978
  • GO:0000979
  • GO:0000981
  • GO:0001227
  • GO:0001228
  • GO:0001541
  • GO:0001889
  • GO:0001892
  • GO:0003677
  • GO:0003682
  • GO:0003700
  • GO:0005515
  • GO:0005634
  • GO:0005654
  • GO:0005737
  • GO:0006351
  • GO:0006355
  • GO:0006357
  • GO:0006366
  • GO:0007613
  • GO:0010628
  • GO:0016363
  • GO:0019900
  • GO:0030154
  • GO:0030182
  • GO:0031490
  • GO:0032496
  • GO:0032675
  • GO:0032753
  • GO:0033598
  • GO:0034976
  • GO:0035035
  • GO:0035259
  • GO:0036488
  • GO:0042130
  • GO:0042742
  • GO:0042802
  • GO:0042803
  • GO:0042826
  • GO:0043524
  • GO:0043565
  • GO:0044389
  • GO:0045444
  • GO:0045595
  • GO:0045600
  • GO:0045669
  • GO:0045670
  • GO:0045892
  • GO:0045893
  • GO:0045944
  • GO:0046982
  • GO:0048856
  • GO:0050729
  • GO:0050873
  • GO:0050877
  • GO:0060644
  • GO:0061515
  • GO:0061629
  • GO:0070059
  • GO:0070169
  • GO:0071222
  • GO:0071230
  • GO:0071347
  • GO:0072574
  • GO:0090575
  • GO:0097421
  • GO:0098542
  • GO:0120162
  • GO:0140297
  • GO:1901329
  • GO:1990647
  • GO:1990837
  • GO:2000120
  • GO:2001198
  • ILMN_2756435
  • mMC020248
  • x62600_s_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • CEBPB_MOUSE
sequenceLength 296
species [Species:48892] Mus musculus
stId uniprot:P28033
url http://purl.uniprot.org/uniprot/P28033
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