UniProtKB - P05554 (CEBPA_RAT)
CCAAT/enhancer-binding protein alpha
Cebpa
Functioni
Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta (PubMed:8367486, PubMed:11672531, PubMed:16735515, PubMed:20176812).
Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes. During early embryogenesis, plays essential and redundant functions with CEBPB (By similarity).
Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP) (PubMed:11672531).
Critical for the proper development of the liver and the lung (By similarity).
Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (PubMed:11672531).
To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Down-regulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters (PubMed:11672531).
Proliferation arrest also depends on a functional binding to SWI/SNF complex (By similarity).
In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity).
By similarity4 PublicationsCan act as dominant-negative. Binds DNA and have transctivation activity, even if much less efficiently than isoform 2. Does not inhibit cell proliferation.
By similarity1 PublicationDirectly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.
By similarityMiscellaneous
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 285 – 300 | 1 PublicationAdd BLAST | 16 |
GO - Molecular functioni
- chromatin binding Source: RGD
- chromatin DNA binding Source: RGD
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor activity Source: RGD
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: RGD
- DNA-binding transcription factor binding Source: UniProtKB
- histone deacetylase binding Source: RGD
- HMG box domain binding Source: UniProtKB
- identical protein binding Source: RGD
- kinase binding Source: RGD
- protein-containing complex binding Source: RGD
- protein domain specific binding Source: RGD
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: RGD
- RNA polymerase I transcription regulatory region sequence-specific DNA binding Source: UniProtKB
- sequence-specific DNA binding Source: UniProtKB
- STAT family protein binding Source: RGD
- transcription cis-regulatory region binding Source: RGD
GO - Biological processi
- acute-phase response Source: RGD
- animal organ regeneration Source: RGD
- brown fat cell differentiation Source: RGD
- cell differentiation Source: RGD
- cell maturation Source: RGD
- cellular response to lithium ion Source: RGD
- cellular response to organic cyclic compound Source: RGD
- cellular response to tumor necrosis factor Source: RGD
- cellular response to xenobiotic stimulus Source: RGD
- cholesterol metabolic process Source: RGD
- embryonic placenta development Source: RGD
- fat cell differentiation Source: UniProtKB
- glucose homeostasis Source: UniProtKB
- granulocyte differentiation Source: UniProtKB
- inner ear development Source: RGD
- interleukin-6-mediated signaling pathway Source: RGD
- lipid homeostasis Source: UniProtKB
- liver development Source: RGD
- lung development Source: UniProtKB
- macrophage differentiation Source: RGD
- memory Source: RGD
- mitochondrion organization Source: RGD
- myeloid cell differentiation Source: RGD
- negative regulation of cell cycle Source: RGD
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: ComplexPortal
- Notch signaling pathway Source: RGD
- osteoblast development Source: RGD
- positive regulation of fat cell differentiation Source: RGD
- positive regulation of gene expression Source: RGD
- positive regulation of inflammatory response Source: RGD
- positive regulation of macrophage activation Source: RGD
- positive regulation of osteoblast differentiation Source: RGD
- positive regulation of transcription, DNA-templated Source: RGD
- positive regulation of transcription by RNA polymerase II Source: NTNU_SB
- positive regulation of transcription by RNA polymerase III Source: RGD
- regulation of cell population proliferation Source: RGD
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: RGD
- response to dexamethasone Source: RGD
- response to nutrient Source: RGD
- response to phenylpropanoid Source: RGD
- response to vitamin B2 Source: RGD
- transcription by RNA polymerase I Source: UniProtKB
- urea cycle Source: RGD
- white fat cell differentiation Source: RGD
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-RNO-9616222, Transcriptional regulation of granulopoiesis |
Names & Taxonomyi
Protein namesi | Recommended name: CCAAT/enhancer-binding protein alphaImportedShort name: C/EBP alpha |
Gene namesi | Name:CebpaImported |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 2326, Cebpa |
Subcellular locationi
Nucleus
- C/EBP complex Source: RGD
- CHOP-C/EBP complex Source: ParkinsonsUK-UCL
- nuclear matrix Source: RGD
- nucleolus Source: UniProtKB
- nucleus Source: UniProtKB
- Rb-E2F complex Source: RGD
- RNA polymerase II transcription regulator complex Source: RGD
Other locations
- protein-containing complex Source: RGD
- transcription regulator complex Source: RGD
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 159 | K → A or R: Not sumoylated. No effect of sumoylation on cell cycle inhibition. 1 Publication | 1 | |
Mutagenesisi | 285 | Y → A: Decreased transcription factor activity. Strongly decreased transcription factor activity; when associated with R-293. 1 Publication | 1 | |
Mutagenesisi | 285 | Y → A: Increases interaction with TFDP1 and TFDP2, reduces DNA-binding, transactivation activity and represses E2F1:TFDP1-mediated transcription, loss of cell cycle inhibition and adipogenesis induction. 2 Publications | 1 | |
Mutagenesisi | 287 | V → A: No effect on repression of E2F1:TFDP1-mediated transcription, no effect on cell cycle inhibition or adipogenesis; when associated with A-290. 1 Publication | 1 | |
Mutagenesisi | 289 | R → A: Loss of DNA-binding and transcription factor activity. 1 Publication | 1 | |
Mutagenesisi | 290 | E → A: No effect on repression of E2F1:TFDP1-mediated transcription, no effect on cell cycle inhibition or adipogenesis; when associated with A-287. 1 Publication | 1 | |
Mutagenesisi | 293 | N → R: Decreased transcription factor activity. Strongly decreased transcription factor activity; when associated with A-285. 1 Publication | 1 | |
Mutagenesisi | 294 | I → A: Increases interaction with TFDP1 and TFDP2, reduces transactivation activity and represses E2F1:TFDP1-mediated transcription, loss of cell cycle inhibition and adipogenesis induction, no effect on DNA-binding; when associated with A-297. 2 Publications | 1 | |
Mutagenesisi | 296 | V → A: No effect on DNA-binding and transcription factor activity, but modified sequence specificity. 1 Publication | 1 | |
Mutagenesisi | 297 | R → A: Increases interaction with TFDP1 and TFDP2, reduces transactivation activity and represses E2F1:TFDP1-mediated transcription, loss of cell cycle inhibition and adipogenesis induction, no effect on DNA-binding; when associated with A-294. 2 Publications | 1 | |
Mutagenesisi | 299 | S → D: Isoform 4: Stimulates nucleolar retention of isoform 4. No effect on interaction with NPM1, TAF1A and UBTF. 1 Publication | 1 | |
Mutagenesisi | 301 | D → A: No effect neither on interaction with TFDP1 or TFDP2 nor on transactivation activity or repression of E2F1:TFDP1-mediated transcription, no effect on cell cycle inhibition or adipogenesis; when associated with A-304. 2 Publications | 1 | |
Mutagenesisi | 304 | K → A: No effect neither on interaction with TFDP1 or TFDP2 nor on transactivation activity or repression of E2F1:TFDP1-mediated transcription, no effect on cell cycle inhibition or adipogenesis; when associated with A-301. 2 Publications | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076615 | 1 – 358 | CCAAT/enhancer-binding protein alphaAdd BLAST | 358 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 159 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 159 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication | ||
Cross-linki | 159 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity | ||
Modified residuei | 193 | PhosphoserineBy similarity | 1 | |
Modified residuei | 222 | Phosphothreonine; by GSK3By similarity | 1 | |
Modified residuei | 226 | Phosphothreonine; by GSK3By similarity | 1 | |
Modified residuei | 230 | Phosphoserine; by GSK3By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P05554 |
PRIDEi | P05554 |
PTM databases
iPTMneti | P05554 |
PhosphoSitePlusi | P05554 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Genevisiblei | P05554, RN |
Interactioni
Subunit structurei
Binds DNA as a homodimer and as a heterodimer (PubMed:1884998, PubMed:8367486, PubMed:12578822). Can form stable heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (PubMed:1884998, PubMed:1377818). Can form stable homodimers (also isoform 2 and isoform 3 dimers) and heterodimers with CEBPB (with isoform 2 and isoform 3) and CEBPG (PubMed:1377818, PubMed:8367486).
Interacts with PRDM16 (By similarity).
Interacts with UBN1 (By similarity).
Interacts with ZNF638; this interaction increases transcriptional activation (By similarity).
Interacts with the complex TFDP2:E2F1; the interaction prevents CEBPA binding to target gene promoters and represses its transcriptional activity (By similarity).
Interacts with RB1 (By similarity).
Interacts (when phosphorylated at SER-193) with CDK2, CDK4, E2F4 and SMARCA2 (By similarity).
Interacts with SREBPF1 (By similarity).
Interacts with FOXO1 (via the Fork-head domain); the interaction increases when FOXO1 is deacetylated (By similarity).
Interacts with SIX1 (By similarity).
Interacts (via recognition sequence) with TRIB1 (By similarity).
By similarity5 PublicationsGO - Molecular functioni
- DNA-binding transcription factor binding Source: UniProtKB
- histone deacetylase binding Source: RGD
- HMG box domain binding Source: UniProtKB
- identical protein binding Source: RGD
- kinase binding Source: RGD
- protein domain specific binding Source: RGD
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: RGD
- STAT family protein binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 246437, 148 interactors |
ComplexPortali | CPX-60, bZIP transcription factor complex, Cebpa-Ddit3 CPX-64, bZIP transcription factor complex, Cebpa-Cebpa |
DIPi | DIP-28138N |
IntActi | P05554, 5 interactors |
STRINGi | 10116.ENSRNOP00000063123 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P05554 |
SMRi | P05554 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P05554 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 282 – 345 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 70 | Required to repress E2F1:TFDP1-mediated transcription, to inhibit cell cycle and to induce adipocyte differentiation1 PublicationAdd BLAST | 70 | |
Regioni | 1 – 55 | DisorderedSequence analysisAdd BLAST | 55 | |
Regioni | 54 – 72 | Required for interaction with TRIB1By similarityAdd BLAST | 19 | |
Regioni | 126 – 200 | Required to induce adipocyte differentiation1 PublicationAdd BLAST | 75 | |
Regioni | 176 – 195 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 180 – 194 | Required to functionally cooperate with SREBF1 in promoter activationBy similarityAdd BLAST | 15 | |
Regioni | 213 – 310 | DisorderedSequence analysisAdd BLAST | 98 | |
Regioni | 240 – 358 | Interaction with FOXO1By similarityAdd BLAST | 119 | |
Regioni | 286 – 313 | Basic motifPROSITE-ProRule annotationAdd BLAST | 28 | |
Regioni | 317 – 345 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 29 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 36 – 50 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 177 – 194 | Pro residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 218 – 238 | Pro residuesSequence analysisAdd BLAST | 21 | |
Compositional biasi | 277 – 309 | Basic and acidic residuesSequence analysisAdd BLAST | 33 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3119, Eukaryota |
HOGENOMi | CLU_043327_2_0_1 |
InParanoidi | P05554 |
OrthoDBi | 1284308at2759 |
PhylomeDBi | P05554 |
TreeFami | TF105008 |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR046347, bZIP_sf IPR016468, C/EBP_chordates |
Pfami | View protein in Pfam PF07716, bZIP_2, 1 hit |
PIRSFi | PIRSF005879, CCAAT/enhancer-binding, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
SUPFAMi | SSF57959, SSF57959, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative initiation. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MESADFYEAE PRPPMSSHLQ SPPHAPSNAA FGFPRGAGPA PPPAPPAAPE
60 70 80 90 100
PLGGICEHET SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAAGPAGG
110 120 130 140 150
GGDFDYPGAP AGPGGAVMSA GAHGPPPGYG CAAAGYLDGR LEPLYERVGA
160 170 180 190 200
PALRPLVIKQ EPREEDEAKQ LALAGLFPYQ PPPPPPPPHP HASPAHLAAP
210 220 230 240 250
HLQFQIAHCG QTTMHLQPGH PTPPPTPVPS PHPAPAMGAA GLPGPGGSLK
260 270 280 290 300
GLAGPHPDLR TGGGGGGGAG AGKAKKSVDK NSNEYRVRRE RNNIAVRKSR
310 320 330 340 350
DKAKQRNVET QQKVLELTSD NDRLRKRVEQ LSRELDTLRG IFRQLPESSL
VKAMGNCA
The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MRGRGRVGVLGGRRRQRRHAQAGGRRGSPCRENSNSPM
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_057551 | 1 – 117 | Missing in isoform 3. 1 PublicationAdd BLAST | 117 | |
Alternative sequenceiVSP_057552 | 1 – 14 | Missing in isoform 2. 1 PublicationAdd BLAST | 14 | |
Alternative sequenceiVSP_057609 | 1 | M → MRGRGRVGVLGGRRRQRRHA QAGGRRGSPCRENSNSPM in isoform 4. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X12752 Genomic DNA Translation: CAA31242.1 AC109741 Genomic DNA No translation available. |
PIRi | S06890, A54265 |
RefSeqi | NP_001274506.1, NM_001287577.1 [P05554-4] NP_001274507.1, NM_001287578.1 [P05554-2] NP_001274508.1, NM_001287579.1 [P05554-3] NP_036656.1, NM_012524.3 [P05554-1] |
Genome annotation databases
GeneIDi | 24252 |
KEGGi | rno:24252 |
UCSCi | RGD:2326, rat [P05554-1] |
Keywords - Coding sequence diversityi
Alternative initiationSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X12752 Genomic DNA Translation: CAA31242.1 AC109741 Genomic DNA No translation available. |
PIRi | S06890, A54265 |
RefSeqi | NP_001274506.1, NM_001287577.1 [P05554-4] NP_001274507.1, NM_001287578.1 [P05554-2] NP_001274508.1, NM_001287579.1 [P05554-3] NP_036656.1, NM_012524.3 [P05554-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1NWQ | X-ray | 2.80 | A/C | 281-340 | [»] | |
AlphaFoldDBi | P05554 | |||||
SMRi | P05554 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 246437, 148 interactors |
ComplexPortali | CPX-60, bZIP transcription factor complex, Cebpa-Ddit3 CPX-64, bZIP transcription factor complex, Cebpa-Cebpa |
DIPi | DIP-28138N |
IntActi | P05554, 5 interactors |
STRINGi | 10116.ENSRNOP00000063123 |
PTM databases
iPTMneti | P05554 |
PhosphoSitePlusi | P05554 |
Proteomic databases
PaxDbi | P05554 |
PRIDEi | P05554 |
Genome annotation databases
GeneIDi | 24252 |
KEGGi | rno:24252 |
UCSCi | RGD:2326, rat [P05554-1] |
Organism-specific databases
CTDi | 1050 |
RGDi | 2326, Cebpa |
Phylogenomic databases
eggNOGi | KOG3119, Eukaryota |
HOGENOMi | CLU_043327_2_0_1 |
InParanoidi | P05554 |
OrthoDBi | 1284308at2759 |
PhylomeDBi | P05554 |
TreeFami | TF105008 |
Enzyme and pathway databases
Reactomei | R-RNO-9616222, Transcriptional regulation of granulopoiesis |
Miscellaneous databases
EvolutionaryTracei | P05554 |
PROi | PR:P05554 |
Gene expression databases
Genevisiblei | P05554, RN |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR046347, bZIP_sf IPR016468, C/EBP_chordates |
Pfami | View protein in Pfam PF07716, bZIP_2, 1 hit |
PIRSFi | PIRSF005879, CCAAT/enhancer-binding, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
SUPFAMi | SSF57959, SSF57959, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CEBPA_RAT | |
Accessioni | P05554Primary (citable) accession number: P05554 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1988 |
Last sequence update: | February 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 173 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families