CEBPA (CCAAT enhancer binding protein alpha)

Gene

• Entrez ID: 1050
• Gene name: CCAAT enhancer binding protein alpha
• Gene symbol: CEBPA
• Synonyms: C/EBP-alpha, CEBP
• Chromosome: 19
• Chromosome location: 19q13.11
• Summary: This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma. Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis. Mutation of this gene is associated with acute myeloid leukemia. The use of alternative in-frame non-AUG (GUG) and AUG start codons results in protein isoforms with different lengths. Differential translation initiation is mediated by an out-of-frame, upstream open reading frame which is located between the GUG and the first AUG start codons. [provided by RefSeq, Dec 2013]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000390	hsa-miR-1-3p	Luciferase reporter assay	18818206
MIRT002025	hsa-miR-124-3p	Luciferase reporter assay, Western blot, Reporter assay	18451139
MIRT002025	hsa-miR-124-3p	Microarray	15685193
MIRT005488	hsa-miR-138-5p	qRT-PCR	20486779
MIRT036497	hsa-miR-1226-3p	CLASH	23622248
MIRT037622	hsa-miR-744-5p	CLASH	23622248
MIRT038606	hsa-miR-193a-5p	CLASH	23622248
MIRT045932	hsa-miR-125b-5p	CLASH	23622248
MIRT045932	hsa-miR-125b-5p	Luciferase reporter assay, qRT-PCR, Western blot	25982911
MIRT734848	hsa-miR-181a-5p	Luciferase reporter assay	27673564

Transcription factors

Transcription factor	Regulation	Reference
DDIT3	Repression	21983012
GATA1	Repression	19825991
LEF1	Unknown	19620402
MYB	Unknown	10706719
MYC	Repression	19259613
MYC	Unknown	15867211
PPARG	Unknown	15867211
ZBTB16	Unknown	19723763

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000050	Process	Urea cycle	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	12695546, 28186500
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	16946298
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	ISS
GO:0001889	Process	Liver development	ISS
GO:0001892	Process	Embryonic placenta development	IEA
GO:0003677	Function	DNA binding	TAS	8643605
GO:0003682	Function	Chromatin binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	11242107, 12695546, 15664994
GO:0005515	Function	Protein binding	IPI	12692227, 15107404, 16490787, 19059241, 20102225, 23814099
GO:0005634	Component	Nucleus	IDA	11242107
GO:0005654	Component	Nucleoplasm	IDA
GO:0005667	Component	Transcription regulator complex	IDA	24429361
GO:0005730	Component	Nucleolus	IEA
GO:0006091	Process	Generation of precursor metabolites and energy	TAS	8643605
GO:0006355	Process	Regulation of transcription, DNA-templated	IDA	15664994
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0007005	Process	Mitochondrion organization	IEA
GO:0007219	Process	Notch signaling pathway	IEA
GO:0008134	Function	Transcription factor binding	IPI	15664994, 24429361
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0008285	Process	Negative regulation of cell population proliferation	IDA	14660596
GO:0008285	Process	Negative regulation of cell population proliferation	ISS
GO:0016032	Process	Viral process	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	NAS	15664994
GO:0019900	Function	Kinase binding	IPI	15107404
GO:0030099	Process	Myeloid cell differentiation	IBA	21873635
GO:0030099	Process	Myeloid cell differentiation	NAS	15664994
GO:0030225	Process	Macrophage differentiation	IEA
GO:0030324	Process	Lung development	ISS
GO:0030851	Process	Granulocyte differentiation	ISS
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	TAS	14685163
GO:0042593	Process	Glucose homeostasis	ISS
GO:0042803	Function	Protein homodimerization activity	ISS
GO:0043032	Process	Positive regulation of macrophage activation	ISS
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0045444	Process	Fat cell differentiation	ISS
GO:0045600	Process	Positive regulation of fat cell differentiation	IEA
GO:0045669	Process	Positive regulation of osteoblast differentiation	IEA
GO:0045736	Process	Negative regulation of cyclin-dependent protein serine/threonine kinase activity	TAS	14685163
GO:0045892	Process	Negative regulation of transcription, DNA-templated	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	7959007, 20972335
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IGI	24429361
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	16946298
GO:0045945	Process	Positive regulation of transcription by RNA polymerase III	IDA	12695546
GO:0048469	Process	Cell maturation	IEA
GO:0048839	Process	Inner ear development	IEA
GO:0050729	Process	Positive regulation of inflammatory response	ISS
GO:0050872	Process	White fat cell differentiation	IEA
GO:0050873	Process	Brown fat cell differentiation	IEA
GO:0055088	Process	Lipid homeostasis	ISS
GO:0070102	Process	Interleukin-6-mediated signaling pathway	IDA	24429361
GO:0071285	Process	Cellular response to lithium ion	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071407	Process	Cellular response to organic cyclic compound	IEA
GO:0090575	Component	RNA polymerase II transcription regulator complex	IMP	16946298

Other IDs

• MIM: 116897
• HGNC: 1833
• e!Ensembl: ENSG00000245848

Protein

• UniProt ID: P49715
• Protein name: CCAAT/enhancer-binding protein alpha (C/EBP alpha)
• Protein function: 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 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). ; [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). ; [Isoform 4]: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.
• PDB: 6DC0
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07716	bZIP_2	281 → 334	Basic region leucine zipper	Coiled-coil

• Sequence:

  MESADFYEAEPRPPMSSHLQSPPHAPSSAAFGFPRGAGPAQPPAPPAAPEPLGGICEHET
  SIDISAYIDPAAFNDEFLADLFQHSRQQEKAKAAVGPTGGGGGGDFDYPGAPAGPGGAVM
  PGGAHGPPPGYGCAAAGYLDGRLEPLYERVGAPALRPLVIKQEPREEDEAKQLALAGLFP
  YQPPPPPPPSHPHPHPPPAHLAAPHLQFQIAHCGQTTMHLQPGHPTPPPTPVPSPHPAPA
  LGAAGLPGPGSALKGLGAAHPDLRASGGSGAGKAKKSVDKNSNEYRVRRERNNIAVRKSR
  DKAKQRNVETQQKVLELTSDNDRLRKRVEQLSRELDTLRGIFRQLPESSLVKAMGNCA

• Sequence length: 358