EP300

See also: p300-CBP coactivator family

E1A binding protein p300
PDB rendering based on 1f81.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1L3E, 1P4Q, 2K8F, 2MH0, 2MZD, 3BIY, 3I3J, 3IO2, 3P57, 3T92, 4BHW, 4PZR, 4PZS, 4PZT
Identifiers
Symbols	EP300 ; KAT3B; RSTS2; p300
External IDs	OMIM: 602700 MGI: 1276116 HomoloGene: 1094 ChEMBL: 3784 GeneCards: EP300 Gene
EC number	2.3.1.48
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • core promoter binding • RNA polymerase II activating transcription factor binding • RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription • p53 binding • DNA binding • chromatin binding • damaged DNA binding • transcription coactivator activity • histone acetyltransferase activity • lysine N-acetyltransferase activity, acting on acetyl phosphate as donor • protein binding • beta-catenin binding • protein C-terminus binding • transcription factor binding • zinc ion binding • acetyltransferase activity • transferase activity, transferring acyl groups • chromatin DNA binding • protein complex binding • activating transcription factor binding • nuclear hormone receptor binding • glucocorticoid receptor binding • peroxisome proliferator activated receptor binding • bHLH transcription factor binding • SMAD binding • androgen receptor binding • mitogen-activated protein kinase binding • NF-kappaB binding • pre-mRNA intronic binding • protein antigen binding Cellular component • histone acetyltransferase complex • chromatin • nucleus • nucleoplasm • transcription factor complex • cytoplasm • protein-DNA complex Biological process • G2/M transition of mitotic cell cycle • negative regulation of transcription from RNA polymerase II promoter • mitotic cell cycle • response to hypoxia • somitogenesis • liver development • positive regulation of protein phosphorylation • stimulatory C-type lectin receptor signaling pathway • chromatin organization • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • protein acetylation • internal protein amino acid acetylation • apoptotic process • positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response • Notch signaling pathway • nervous system development • heart development • skeletal muscle tissue development • memory • circadian rhythm • organ morphogenesis • positive regulation of glycoprotein biosynthetic process • positive regulation of cell death • positive regulation of muscle atrophy • viral process • N-terminal peptidyl-lysine acetylation • internal peptidyl-lysine acetylation • lung development • response to cobalt ion • positive regulation of protein binding • positive regulation of type I interferon production • positive regulation of collagen biosynthetic process • positive regulation of protein import into nucleus, translocation • cellular response to heat • response to tumor necrosis factor • cellular response to UV • positive regulation of histone acetylation • cellular response to drug • cellular response to trichostatin A • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of DNA binding • protein kinase B signaling • response to estrogen • positive regulation by host of viral transcription • histone H3 acetylation • histone H4 acetylation • histone H2B acetylation • innate immune response • response to ethanol • positive regulation of translation • positive regulation of axon extension • positive regulation of cell size • positive regulation of proteolysis • positive regulation of transcription from RNA polymerase II promoter • digestive tract development • positive regulation of protein secretion • protein stabilization • positive regulation of sequence-specific DNA binding transcription factor activity • response to calcium ion • regulation of cell cycle • regulation of angiotensin metabolic process • positive regulation of sarcomere organization • regulation of androgen receptor signaling pathway • regulation of transcription from RNA polymerase II promoter in response to hypoxia • protein-DNA complex assembly • cellular response to hydrogen peroxide • response to fatty acid • cellular response to retinoic acid • cellular response to cAMP • cellular response to glucose stimulus • cellular response to mineralocorticoid stimulus • cellular response to hypoxia • cellular response to dexamethasone stimulus • regulation of tubulin deacetylation • regulation of cellular response to heat • cellular response to nerve growth factor stimulus • negative regulation of miRNA metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2033	328572
Ensembl	ENSG00000100393	ENSMUSG00000055024
UniProt	Q09472	B2RWS6
RefSeq (mRNA)	NM_001429	NM_177821
RefSeq (protein)	NP_001420	NP_808489
Location (UCSC)	Chr 22: 41.09 – 41.18 Mb	Chr 15: 81.59 – 81.65 Mb
PubMed search	[2]	[3]

E1A binding protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene. This protein regulates the activity of many genes in tissues throughout the body. It plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.

The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2.

EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16.

Function

This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein.

The protein functions as histone acetyltransferase that regulates transcription via chromatin remodeling, and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein.

This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and, thus, plays a role in the stimulation of hypoxia-induced genes such as VEGF.

Mechanism

The p300 protein carries out its function by activating transcription. To be specific, p300 connects transcription factors, which are proteins that start the transcription process, with the complex of proteins that carry out transcription in the cell's nucleus. On the basis of this function, p300 is called a transcriptional coactivator. The p300 interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor interaction domain (RID), the CREB and MYB interaction domain (KIX), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). The last four domains, KIX, TAZ1, TAZ2 and IBiD of p300, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53.

Clinical significance

Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein-Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.

Chromosomal rearrangements involving chromosome 22 have rarely been associated with certain types of cancer. These rearrangements, called translocations, disrupt the region of chromosome 22 that contains the EP300 gene. For example, researchers have found a translocation between chromosomes 8 and 22 in several people with a cancer of blood cells called acute myeloid leukemia (AML). Another translocation, involving chromosomes 11 and 22, has been found in a small number of people who have undergone cancer treatment. This chromosomal change is associated with the development of AML following chemotherapy for other forms of cancer.

Mutations in the EP300 gene have been identified in several other types of cancer. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. Somatic mutations in the EP300 gene have been found in a small number of solid tumors, including cancers of the colon and rectum, stomach, breast, and pancreas. Studies suggest that EP300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, EP300 mutations prevent the gene from producing any functional protein. Without p300, cells cannot effectively restrain growth and division, which can allow cancerous tumors to form.

Interactions

EP300 has been shown to interact with:

• BCL3,
• BRCA1,
• CDX2,
• CEBPB,
• CITED1,
• CITED2,
• DDX5,
• DTX1,
• EID1,
• ELK1,
• ESR1,
• FEN1,
• GPS2,
• HIF1A,
• HNF1A,
• HNRPU,
• ING4,
• ING5,
• IRF2,
• LEF1,
• MAF,
• MAML1,
• MEF2C,
• MEF2D,
• MYBL2,
• Mdm2,
• MyoD,
• MEF2A,
• NCOA6,
• NFATC2,
• NPAS2,
• P53,
• PAX6,
• PCNA,
• PROX1,
• PTMA,
• PPARA,
• PPARG,
• RORA,
• RELA,
• SMAD1,
• SMAD2,
• SMAD7,
• SNIP1,
• SS18,
• STAT3,
• STAT6,
• TAL1,
• TCF3,
• TFAP2A,
• TGS1,
• TRERF1,
• TSG101,
• THRA,
• TWIST1,
• YY1, and
• Zif268.

External links

• GeneReviews/NCBI/NIH/UW entry on Rubinstein-Taybi Syndrome
• GeneCard
• EP300 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C54
• FactorBook P300

This article incorporates text from the United States National Library of Medicine, which is in the public domain.