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UniProtKB - P49715 (CEBPA_HUMAN)

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Protein

CCAAT/enhancer-binding protein alpha

Gene

CEBPA

Organism
Homo sapiens (Human)
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. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes (PubMed:11242107). During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). 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 (By similarity). 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. Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). 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 similarity2 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 (PubMed:14660596).By similarity1 Publication
Isoform 4: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi285 – 300By similarityAdd BLAST16

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processHost-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-381340 Transcriptional regulation of white adipocyte differentiation
SignaLinkiP49715
SIGNORiP49715

Names & Taxonomyi

Protein namesi
Recommended name:
CCAAT/enhancer-binding protein alphaImported
Short name:
C/EBP alphaImported
Gene namesi
Name:CEBPAImported
Synonyms:CEBPImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000245848.2
HGNCiHGNC:1833 CEBPA
MIMi116897 gene
neXtProtiNX_P49715

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

Involvement in diseasei

Leukemia, acute myelogenous (AML)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
See also OMIM:601626
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07267784H → L in AML; no effect on expression; no effect on DNA-binding or transactivation activity. 1 PublicationCorresponds to variant dbSNP:rs28931590EnsemblClinVar.1
Natural variantiVAR_072678312Q → QK in AML; nuclear; no effect on expression; loss of DNA-binding and transactivation activity. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi55I → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi57E → T: No effect on interaction with TRIB1. 1 Publication1
Mutagenesisi58H → D: No effect on interaction with TRIB1. 1 Publication1
Mutagenesisi59E → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi61S → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi62I → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi63D → A: No effect on interaction with TRIB1. 1 Publication1
Mutagenesisi64I → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi65S → A: No effect on interaction with TRIB1. 1 Publication1
Mutagenesisi67Y → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi67Y → F: No effect on interaction with TRIB1. 1 Publication1
Mutagenesisi68I → A: Decreased interaction with TRIB1. 1 Publication1
Mutagenesisi69D → A: No effect on interaction with TRIB1. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1050
GeneReviewsiCEBPA
MalaCardsiCEBPA
MIMi601626 phenotype
OpenTargetsiENSG00000245848
Orphaneti102724 'Acute myeloid leukemia with t(8;21)(q22;q22) translocation'
319480 Acute myeloid leukemia with CEBPA somatic mutations
319465 Inherited acute myeloid leukemia
PharmGKBiPA26376

Polymorphism and mutation databases

DMDMi166898082

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766131 – 358CCAAT/enhancer-binding protein alphaAdd BLAST358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei161N6-acetyllysine; alternateCombined sources1
Cross-linki161Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei190Phosphoserine1 Publication1
Modified residuei226Phosphothreonine; by GSK3By similarity1
Modified residuei230Phosphothreonine; by GSK3By similarity1
Modified residuei234Phosphoserine; by GSK3By similarity1

Post-translational modificationi

Phosphorylation at Ser-190 is required for interaction with CDK2, CDK4 and SWI/SNF complex leading to cell cycle inhibition. Dephosphorylated at Ser-190 by protein phosphatase 2A (PP2A) through PI3K/AKT signaling pathway regulation (PubMed:15107404). Phosphorylation at Thr-226 and Thr-230 by GSK3 is constitutive in adipose tissue and lung. In liver, both Thr-226 and Thr-230 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
Sumoylated, sumoylation blocks the inhibitory effect on cell proliferation by disrupting the interaction with SMARCA2.By similarity
Ubiquitinated by COP1 upon interaction with TRIB1.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49715
MaxQBiP49715
PaxDbiP49715
PeptideAtlasiP49715
PRIDEiP49715
ProteomicsDBi56054

PTM databases

iPTMnetiP49715
PhosphoSitePlusiP49715

Expressioni

Gene expression databases

BgeeiENSG00000245848
CleanExiHS_CEBPA
GenevisibleiP49715 HS

Organism-specific databases

HPAiHPA052734
HPA065037
HPA067937

Interactioni

Subunit structurei

Binds DNA as a homodimer and as a heterodimer. Can form stable heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (By similarity). Interacts with PRDM16 (By similarity). Interacts with UBN1 (PubMed:10725330). 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 (PubMed:20176812). Interacts with RB1 (PubMed:15107404). Interacts (when phosphorylated at SER-190) with CDK2, CDK4, E2F4 and SMARCA2 (PubMed:15107404). 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 interacts with TAF1A and UBTF (PubMed:20075868). Isoform 4 interacts with NPM1 (PubMed:20075868). Interacts (via recognition sequence) with TRIB1 (PubMed:20410507, PubMed:26455797).By similarity6 Publications
(Microbial infection) Interacts with HBV protein X.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi107479, 97 interactors
ComplexPortaliCPX-69 CHOP-C/EBPalpha complex
CPX-71 C/EBPalpha complex
CORUMiP49715
DIPiDIP-37882N
ELMiP49715
IntActiP49715, 23 interactors
MINTiP49715
STRINGi9606.ENSP00000427514

Structurei

3D structure databases

ProteinModelPortaliP49715
SMRiP49715
ModBaseiSearch...
MobiDBiSearch...

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 differentiationBy similarityAdd BLAST70
Regioni54 – 72Required for interaction with TRIB11 PublicationAdd BLAST19
Regioni128 – 204Required to induce adipocyte differentiationBy similarityAdd BLAST77
Regioni182 – 198Required to functionally cooperate with SREBF1 in promoter activationBy similarityAdd BLAST17
Regioni244 – 358Interaction with FOXO1By similarityAdd BLAST115
Regioni286 – 313Basic motifPROSITE-ProRule annotationAdd BLAST28
Regioni317 – 345Leucine-zipperPROSITE-ProRule annotationAdd BLAST29

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi99 – 104Poly-Gly6
Compositional biasi183 – 189Poly-Pro7

Domaini

The recognition sequence (54-72) is required for interaction with TRIB1.1 Publication

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG3119 Eukaryota
ENOG410YJ8G LUCA
GeneTreeiENSGT00530000063192
HOGENOMiHOG000013112
HOVERGENiHBG050879
InParanoidiP49715
KOiK09055
OMAiQIAHCAQ
OrthoDBiEOG091G11FC
PhylomeDBiP49715
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: P49715-1) [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 SPPHAPSSAA FGFPRGAGPA QPPAPPAAPE 
        60         70         80         90        100
PLGGICEHET SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAVGPTGG 
       110        120        130        140        150
GGGGDFDYPG APAGPGGAVM PGGAHGPPPG YGCAAAGYLD GRLEPLYERV 
       160        170        180        190        200
GAPALRPLVI KQEPREEDEA KQLALAGLFP YQPPPPPPPS HPHPHPPPAH 
       210        220        230        240        250
LAAPHLQFQI AHCGQTTMHL QPGHPTPPPT PVPSPHPAPA LGAAGLPGPG 
       260        270        280        290        300
SALKGLGAAH PDLRASGGSG AGKAKKSVDK NSNEYRVRRE RNNIAVRKSR 
       310        320        330        340        350
DKAKQRNVET QQKVLELTSD NDRLRKRVEQ LSRELDTLRG IFRQLPESSL 

VKAMGNCA
Length:358
Mass (Da):37,561
Last modified:February 5, 2008 - v3
Checksum:i574C0A049E25BCAC
GO
Isoform 2 (identifier: P49715-2) [UniParc]FASTAAdd to basket
Also known as: C/EBPalpha-p421 Publication

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

Show »
Length:344
Mass (Da):35,940
Checksum:i49EB5DC3749152A6
GO
Isoform 3 (identifier: P49715-3) [UniParc]FASTAAdd to basket
Also known as: C/EBPalpha-p301 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.

Show »
Length:239
Mass (Da):25,540
Checksum:i4A9F7812303016A0
GO
Isoform 4 (identifier: P49715-4) [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 → MRGRGRAGSPGGRRRRPAQAGGRRGSPCRENSNSPM

Show »
Length:393
Mass (Da):41,249
Checksum:i123630D5A4AD5634
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40 – 41AQ → PK in AAC50235 (PubMed:7575576).Curated2
Sequence conflicti95 – 98VGPT → WAH in CAA72289 (Ref. 2) Curated4
Sequence conflicti241L → V in CAA72289 (Ref. 2) Curated1
Sequence conflicti248 – 250GPG → ALA in CAA72289 (Ref. 2) Curated3
Sequence conflicti269S → T in AAC50235 (PubMed:7575576).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07267784H → L in AML; no effect on expression; no effect on DNA-binding or transactivation activity. 1 PublicationCorresponds to variant dbSNP:rs28931590EnsemblClinVar.1
Natural variantiVAR_072678312Q → QK in AML; nuclear; no effect on expression; loss of DNA-binding and transactivation activity. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0575471 – 119Missing in isoform 3. Add BLAST119
Alternative sequenceiVSP_0575481 – 14Missing in isoform 2. Add BLAST14
Alternative sequenceiVSP_0576071M → MRGRGRAGSPGGRRRRPAQA GGRRGSPCRENSNSPM in isoform 4. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U34070 Genomic DNA Translation: AAC50235.1
Y11525 mRNA Translation: CAA72289.1
EU048234 Genomic DNA Translation: ABS82765.1
AC008738 Genomic DNA No translation available.
BC027902 mRNA Translation: AAH27902.1
CCDSiCCDS54243.1 [P49715-1]
PIRiJC4311
RefSeqiNP_001272758.1, NM_001285829.1 [P49715-3]
NP_001274353.1, NM_001287424.1 [P49715-4]
NP_001274364.1, NM_001287435.1 [P49715-2]
NP_004355.2, NM_004364.4 [P49715-1]
UniGeneiHs.76171

Genome annotation databases

EnsembliENST00000498907; ENSP00000427514; ENSG00000245848 [P49715-1]
GeneIDi1050
KEGGihsa:1050
UCSCiuc002nun.4 human [P49715-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Entry informationi

Entry nameiCEBPA_HUMAN
AccessioniPrimary (citable) accession number: P49715
Secondary accession number(s): A7LNP2, P78319, Q05CA4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 5, 2008
Last modified: July 18, 2018
This is version 178 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. SIMILARITY comments
    Index of protein domains and families

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