InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EP300

Summary

InnateDB Protein

IDBP-8994.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EP300

Protein Name

E1A binding protein p300

Synonyms

KAT3B; p300; RSTS2;

Species

Homo sapiens

Ensembl Protein

ENSP00000263253

InnateDB Gene

IDBG-8992 (EP300)

Protein Structure

UniProt Annotation

Function

Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac). Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity. Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity. Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter. Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity. {ECO:0000269PubMed:10733570, ECO:0000269PubMed:11430825, ECO:0000269PubMed:11701890, ECO:0000269PubMed:12402037, ECO:0000269PubMed:12586840, ECO:0000269PubMed:12929931, ECO:0000269PubMed:14645221, ECO:0000269PubMed:15186775, ECO:0000269PubMed:15890677, ECO:0000269PubMed:16617102, ECO:0000269PubMed:16762839, ECO:0000269PubMed:18722353, ECO:0000269PubMed:18995842, ECO:0000269PubMed:23415232, ECO:0000269PubMed:23911289}.

Subcellular Localization

Cytoplasm. Nucleus. Note=In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Colocalizes with ROCK2 in the nucleus.

Disease Associations

Note=Defects in EP300 may play a role in epithelial cancer.Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A.Rubinstein-Taybi syndrome 2 (RSTS2) [MIM:613684]: A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients. {ECO:0000269PubMed:15706485}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 721 experimentally validated interaction(s) in this database.
They are also associated with 52 interaction(s) predicted by orthology.

Experimentally validated
Total	721 [view]
Protein-Protein	611 [view]
Protein-DNA	84 [view]
Protein-RNA	0
DNA-DNA	26 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	52 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000979	RNA polymerase II core promoter sequence-specific DNA binding
GO:0001047	core promoter binding
GO:0001085	RNA polymerase II transcription factor binding
GO:0001102	RNA polymerase II activating transcription factor binding
GO:0001159	core promoter proximal region DNA binding
GO:0002039	p53 binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003712	transcription cofactor activity
GO:0003713	transcription coactivator activity
GO:0003823	antigen binding
GO:0004402	histone acetyltransferase activity
GO:0004468	lysine N-acetyltransferase activity
GO:0005515	protein binding
GO:0008013	beta-catenin binding
GO:0008134	transcription factor binding
GO:0008270	zinc ion binding
GO:0016407	acetyltransferase activity
GO:0016746	transferase activity, transferring acyl groups
GO:0019901	protein kinase binding
GO:0031490	chromatin DNA binding
GO:0032403	protein complex binding
GO:0033613	activating transcription factor binding
GO:0035257	nuclear hormone receptor binding
GO:0035259	glucocorticoid receptor binding
GO:0042975	peroxisome proliferator activated receptor binding
GO:0043425	bHLH transcription factor binding
GO:0046332	SMAD binding
GO:0050681	androgen receptor binding
GO:0051019	mitogen-activated protein kinase binding
GO:0051059	NF-kappaB binding
GO:0097157	pre-mRNA intronic binding

Biological Process

GO:0000086	G2/M transition of mitotic cell cycle
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000278	mitotic cell cycle
GO:0001666	response to hypoxia
GO:0001756	somitogenesis
GO:0001889	liver development
GO:0001934	positive regulation of protein phosphorylation
GO:0006325	chromatin organization
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006475	internal protein amino acid acetylation
GO:0006915	apoptotic process
GO:0007219	Notch signaling pathway
GO:0007399	nervous system development
GO:0007507	heart development
GO:0007519	skeletal muscle tissue development
GO:0007623	circadian rhythm
GO:0009749	response to glucose
GO:0009887	organ morphogenesis
GO:0010560	positive regulation of glycoprotein biosynthetic process
GO:0010628	positive regulation of gene expression
GO:0010942	positive regulation of cell death
GO:0014070	response to organic cyclic compound
GO:0014737	positive regulation of muscle atrophy
GO:0016032	viral process
GO:0016573	histone acetylation
GO:0018076	N-terminal peptidyl-lysine acetylation
GO:0018393	internal peptidyl-lysine acetylation
GO:0030307	positive regulation of cell growth
GO:0030324	lung development
GO:0031324	negative regulation of cellular metabolic process
GO:0031325	positive regulation of cellular metabolic process
GO:0032025	response to cobalt ion
GO:0032092	positive regulation of protein binding
GO:0032481	positive regulation of type I interferon production
GO:0032526	response to retinoic acid
GO:0032967	positive regulation of collagen biosynthetic process
GO:0033160	positive regulation of protein import into nucleus, translocation
GO:0034612	response to tumor necrosis factor
GO:0035690	cellular response to drug
GO:0035984	cellular response to trichostatin A
GO:0042493	response to drug
GO:0042542	response to hydrogen peroxide
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043388	positive regulation of DNA binding
GO:0043491	protein kinase B signaling
GO:0043627	response to estrogen
GO:0043923	positive regulation by host of viral transcription
GO:0043966	histone H3 acetylation
GO:0043967	histone H4 acetylation
GO:0043969	histone H2B acetylation
GO:0045087	innate immune response
GO:0045471	response to ethanol
GO:0045727	positive regulation of translation
GO:0045773	positive regulation of axon extension
GO:0045793	positive regulation of cell size
GO:0045862	positive regulation of proteolysis
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048565	digestive tract development
GO:0050714	positive regulation of protein secretion
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051592	response to calcium ion
GO:0051726	regulation of cell cycle
GO:0060177	regulation of angiotensin metabolic process
GO:0060298	positive regulation of sarcomere organization
GO:0060548	negative regulation of cell death
GO:0060765	regulation of androgen receptor signaling pathway
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0065004	protein-DNA complex assembly
GO:0070301	cellular response to hydrogen peroxide
GO:0070542	response to fatty acid
GO:0071236	cellular response to antibiotic
GO:0071300	cellular response to retinoic acid
GO:0071320	cellular response to cAMP
GO:0071333	cellular response to glucose stimulus
GO:0071389	cellular response to mineralocorticoid stimulus
GO:0071407	cellular response to organic cyclic compound
GO:0071456	cellular response to hypoxia
GO:0071548	response to dexamethasone
GO:0071549	cellular response to dexamethasone stimulus
GO:0090043	regulation of tubulin deacetylation
GO:1901985	positive regulation of protein acetylation
GO:1990090	cellular response to nerve growth factor stimulus
GO:2000629	negative regulation of miRNA metabolic process

Cellular Component

GO:0000123	histone acetyltransferase complex
GO:0000785	chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005737	cytoplasm
GO:0032993	protein-DNA complex

Protein Structure and Domains

PDB ID

InterPro

IPR000197 Zinc finger, TAZ-type
IPR000433 Zinc finger, ZZ-type
IPR001487 Bromodomain
IPR003101 Coactivator CBP, KIX domain
IPR009110 Nuclear receptor coactivator, interlocking
IPR010303 Domain of unknown function DUF902, CREBbp
IPR011011 Zinc finger, FYVE/PHD-type
IPR013178 Histone H3-K56 acetyltransferase, RTT109
IPR014744 Nuclear receptor coactivator, CREB-bp-like, interlocking

PFAM