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UniProtKB - P05554 (CEBPA_RAT)

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Protein

CCAAT/enhancer-binding protein alpha

Gene

Cebpa

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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. Downregulates 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 G6PC. 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 Publications
Isoform 3: Can 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 Publication
Isoform 4: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.By similarity

Miscellaneous

The V296A substitution has little effect on the binding of CEBPA to its consensus site (5'-GCAAT-3'), while greatly increasing affinity for cAMP response element (CRE) sites (5'-GTCAT-3').1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi285 – 3001 PublicationAdd BLAST16

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • histone deacetylase binding Source: RGD
  • HMG box domain binding Source: UniProtKB
  • 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 proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase I regulatory region DNA binding Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcription coactivator activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • acute-phase response Source: RGD
  • animal organ regeneration Source: RGD
  • cell differentiation Source: RGD
  • cellular response to drug Source: RGD
  • fat cell differentiation Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • granulocyte differentiation Source: UniProtKB
  • lipid homeostasis Source: UniProtKB
  • liver development Source: RGD
  • lung development Source: UniProtKB
  • memory Source: RGD
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • osteoblast development Source: RGD
  • positive regulation of fat cell differentiation Source: RGD
  • positive regulation of transcription by RNA polymerase II Source: NTNU_SB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • 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
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
CCAAT/enhancer-binding protein alphaImported
Short name:
C/EBP alpha
Gene namesi
Name:CebpaImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2326 Cebpa

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi159K → A or R: Not sumoylated. No effect of sumoylation on cell cycle inhibition. 1 Publication1
Mutagenesisi285Y → A: Decreased transcription factor activity. Strongly decreased transcription factor activity; when associated with R-293. 1 Publication1
Mutagenesisi285Y → 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 Publications1
Mutagenesisi287V → A: No effect on repression of E2F1:TFDP1-mediated transcription, no effect on cell cycle inhibition or adipogenesis; when associated with A-290. 1 Publication1
Mutagenesisi289R → A: Loss of DNA-binding and transcription factor activity. 1 Publication1
Mutagenesisi290E → A: No effect on repression of E2F1:TFDP1-mediated transcription, no effect on cell cycle inhibition or adipogenesis; when associated with A-287. 1 Publication1
Mutagenesisi293N → R: Decreased transcription factor activity. Strongly decreased transcription factor activity; when associated with A-285. 1 Publication1
Mutagenesisi294I → 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 Publications1
Mutagenesisi296V → A: No effect on DNA-binding and transcription factor activity, but modified sequence specificity. 1 Publication1
Mutagenesisi297R → 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 Publications1
Mutagenesisi299S → D: Isoform-4: Stimulates nucleolar retention of isoform-4. No effect on interaction with NPM1, TAF1A and UBTF. 1 Publication1
Mutagenesisi301D → 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 Publications1
Mutagenesisi304K → 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 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766151 – 358CCAAT/enhancer-binding protein alphaAdd BLAST358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei159N6-acetyllysine; alternateBy similarity1
Cross-linki159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei193PhosphoserineBy similarity1
Modified residuei222Phosphothreonine; by GSK3By similarity1
Modified residuei226Phosphothreonine; by GSK3By similarity1
Modified residuei230Phosphoserine; by GSK3By similarity1

Post-translational modificationi

Sumoylated, sumoylation blocks the inhibitory effect on cell proliferation by disrupting the interaction with SMARCA2.1 Publication
Phosphorylation at Ser-193 is required for interaction with CDK2, CDK4 and SWI/SNF complex leading to cell cycle inhibition. Dephosphorylated at Ser-193 by protein phosphatase 2A (PP2A) through PI3K/AKT signaling pathway regulation. Phosphorylation at Thr-222 and Thr-226 by GSK3 is constitutive in adipose tissue and lung. In liver, both Thr-222 and Thr-226 are phosphorylated only during feeding but not during fasting. Phosphorylation of the GSK3 consensus sites selectively decreases transactivation activity on IRE-controlled promoters.By similarity
Ubiquitinated by COP1 upon interaction with TRIB1.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP05554

PTM databases

iPTMnetiP05554
PhosphoSitePlusiP05554

Expressioni

Tissue specificityi

Isoform 2 and isoform 3 are expressed in liver (at protein level).1 Publication

Developmental stagei

Isoform 2 and isoform 3 are not expressed at 1 day before birth, relative concentration of both isoforms increases with the age of the animal, reaching maximal levels in the adulthood.1 Publication

Gene expression databases

GenevisibleiP05554 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). Isoform 1 and Isoform 4 interact with TAF1A and UBTF (PubMed:20075868). Isoform 4 interacts with NPM1 (PubMed:20075868). Interacts (via recognition sequence) with TRIB1 (By similarity).By similarity5 Publications

GO - Molecular functioni

  • histone deacetylase binding Source: RGD
  • HMG box domain binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi246437, 3 interactors
ComplexPortaliCPX-60 CHOP-C/EBPalpha complex
CPX-64 C/EBPalpha complex
DIPiDIP-28138N
IntActiP05554, 5 interactors
STRINGi10116.ENSRNOP00000063123

Structurei

Secondary structure

1358
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi282 – 338Combined sources57

3D structure databases

ProteinModelPortaliP05554
SMRiP05554
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05554

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini282 – 345bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 70Required to repress E2F1:TFDP1-mediated transcription, to inhibit cell cycle and to induce adipocyte differentiation1 PublicationAdd BLAST70
Regioni54 – 72Required for interaction with TRIB1By similarityAdd BLAST19
Regioni126 – 200Required to induce adipocyte differentiation1 PublicationAdd BLAST75
Regioni180 – 194Required to functionally cooperate with SREBF1 in promoter activationBy similarityAdd BLAST15
Regioni240 – 358Interaction with FOXO1By similarityAdd BLAST119
Regioni286 – 313Basic motifPROSITE-ProRule annotationAdd BLAST28
Regioni317 – 345Leucine-zipperPROSITE-ProRule annotationAdd BLAST29

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi181 – 190Poly-Pro10
Compositional biasi262 – 272Poly-GlyAdd BLAST11

Domaini

The recognition sequence (54-72) is required for interaction with TRIB1.By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG3119 Eukaryota
ENOG410YJ8G LUCA
HOGENOMiHOG000013112
HOVERGENiHBG050879
InParanoidiP05554
KOiK09055
OrthoDBiEOG091G11FC
PhylomeDBiP05554
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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P05554-1) [UniParc]FASTAAdd to basket

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
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
Length:358
Mass (Da):37,371
Last modified:February 1, 1996 - v3
Checksum:i4DA8F112F6EA95D0
GO
Isoform 2 (identifier: P05554-2) [UniParc]FASTAAdd to basket
Also known as: CEBPalpha-p421 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Show »
Length:344
Mass (Da):35,750
Checksum:i530FA6D51C5E7BDA
GO
Isoform 3 (identifier: P05554-3) [UniParc]FASTAAdd to basket
Also known as: C/EBPalpha-p301 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: Missing.

Show »
Length:241
Mass (Da):25,526
Checksum:i16713D706888AA35
GO
Isoform 4 (identifier: P05554-4) [UniParc]FASTAAdd to basket
Also known as: extended-C/EBPalpha1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRGRGRVGVLGGRRRQRRHAQAGGRRGSPCRENSNSPM

Note: Mutagenesis in position: 14: RRQR -> AAAA abolishes nucleolar localization and prevents induction of 45S pre-RNA.1 Publication
Show »
Length:395
Mass (Da):41,440
Checksum:i01D1DA74BD4A48C8
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0575511 – 117Missing in isoform 3. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_0575521 – 14Missing in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_0576091M → 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.
PIRiS06890 A54265
RefSeqiNP_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

GeneIDi24252
KEGGirno:24252
UCSCiRGD:2326 rat [P05554-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Entry informationi

Entry nameiCEBPA_RAT
AccessioniPrimary (citable) accession number: P05554
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1996
Last modified: June 20, 2018
This is version 155 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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