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Protein

CCAAT/enhancer-binding protein alpha

Gene

CEBPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:G66-32970-MONOMER.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1833. CEBPA.

Subcellular locationi

Isoform 4 :
  • Nucleusnucleolus 1 Publication

GO - Cellular componenti

  • nucleolus Source: UniProtKB
  • nucleus Source: UniProtKB
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

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 rs28931590dbSNPEnsembl.1
Natural variantiVAR_072678312Q → QK in AML; nuclear; no effect on expression; loss of DNA-binding and transactivation activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1050.
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 inhibiton. 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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49715.
MaxQBiP49715.
PaxDbiP49715.
PeptideAtlasiP49715.
PRIDEiP49715.

PTM databases

iPTMnetiP49715.
PhosphoSitePlusiP49715.

Expressioni

Gene expression databases

BgeeiENSG00000245848.
CleanExiHS_CEBPA.
GenevisibleiP49715. HS.

Organism-specific databases

HPAiHPA065037.

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 with HBV protein X (PubMed:9915821).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATF4P188482EBI-1172054,EBI-492498
CDX1P479023EBI-1172054,EBI-8514176
CEBPBP176762EBI-1172054,EBI-969696
CEBPDP497162EBI-1172054,EBI-7962058
CEBPGP535672EBI-1172054,EBI-740209
DDIT3P356382EBI-1172054,EBI-742651
E2P031222EBI-1172054,EBI-7028618From a different organism.
E2P064224EBI-1172054,EBI-7136851From a different organism.
IL32P24001-27EBI-1172054,EBI-8800907
PARP1P098742EBI-1172054,EBI-355676

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107479. 94 interactors.
DIPiDIP-37882N.
IntActiP49715. 21 interactors.
MINTiMINT-264048.
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
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

Sequence similaritiesi

Belongs to the bZIP family. C/EBP subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3119. Eukaryota.
ENOG410YJ8G. LUCA.
GeneTreeiENSGT00530000063192.
HOGENOMiHOG000013112.
HOVERGENiHBG050879.
InParanoidiP49715.
KOiK09055.
OMAiFDYPGAP.
OrthoDBiEOG091G11FC.
PhylomeDBiP49715.
TreeFamiTF105008.

Family and domain databases

InterProiIPR004827. bZIP.
IPR031106. C/EBP.
IPR016468. C/EBP_chordates.
[Graphical view]
PANTHERiPTHR23334. PTHR23334. 1 hit.
PfamiPF07716. bZIP_2. 1 hit.
[Graphical view]
PIRSFiPIRSF005879. CCAAT/enhancer-binding. 1 hit.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]

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 rs28931590dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
SeattleSNPs

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.

3D structure databases

ProteinModelPortaliP49715.
SMRiP49715.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107479. 94 interactors.
DIPiDIP-37882N.
IntActiP49715. 21 interactors.
MINTiMINT-264048.
STRINGi9606.ENSP00000427514.

PTM databases

iPTMnetiP49715.
PhosphoSitePlusiP49715.

Polymorphism and mutation databases

DMDMi166898082.

Proteomic databases

EPDiP49715.
MaxQBiP49715.
PaxDbiP49715.
PeptideAtlasiP49715.
PRIDEiP49715.

Protocols and materials databases

DNASUi1050.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1050.
DisGeNETi1050.
GeneCardsiCEBPA.
GeneReviewsiCEBPA.
H-InvDBHIX0040095.
HGNCiHGNC:1833. CEBPA.
HPAiHPA065037.
MalaCardsiCEBPA.
MIMi116897. gene.
601626. phenotype.
neXtProtiNX_P49715.
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.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3119. Eukaryota.
ENOG410YJ8G. LUCA.
GeneTreeiENSGT00530000063192.
HOGENOMiHOG000013112.
HOVERGENiHBG050879.
InParanoidiP49715.
KOiK09055.
OMAiFDYPGAP.
OrthoDBiEOG091G11FC.
PhylomeDBiP49715.
TreeFamiTF105008.

Enzyme and pathway databases

BioCyciZFISH:G66-32970-MONOMER.
ReactomeiR-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
SignaLinkiP49715.
SIGNORiP49715.

Miscellaneous databases

ChiTaRSiCEBPA. human.
GeneWikiiCEBPA.
GenomeRNAii1050.
PROiP49715.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000245848.
CleanExiHS_CEBPA.
GenevisibleiP49715. HS.

Family and domain databases

InterProiIPR004827. bZIP.
IPR031106. C/EBP.
IPR016468. C/EBP_chordates.
[Graphical view]
PANTHERiPTHR23334. PTHR23334. 1 hit.
PfamiPF07716. bZIP_2. 1 hit.
[Graphical view]
PIRSFiPIRSF005879. CCAAT/enhancer-binding. 1 hit.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCEBPA_HUMAN
AccessioniPrimary (citable) accession number: P49715
Secondary accession number(s): A7LNP2, P78319, Q05CA4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 5, 2008
Last modified: November 30, 2016
This is version 162 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.