UniProtKB - Q09472 (EP300_HUMAN)
Histone acetyltransferase p300
EP300
Functioni
Functions as histone acetyltransferase and regulates transcription via chromatin remodeling (PubMed:23415232, PubMed:23934153, PubMed:8945521).
Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation (PubMed:23415232, PubMed:23934153, PubMed:8945521).
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) (PubMed:23911289).
Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1 or SIRT2 (PubMed:12929931, PubMed:16762839, PubMed:18722353).
Acetylates 'Lys-131' of ALX1 and acts as its coactivator (PubMed:12929931).
Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of p53/TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (PubMed:18722353).
Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis (PubMed:11511361, PubMed:15448695).
Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription (PubMed:18451878).
Acetylates HDAC1 leading to its inactivation and modulation of transcription (PubMed:16762839).
Acetylates 'Lys-247' of EGR2 (By similarity).
Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2 (PubMed:12586840).
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. Acetylates FOXO1 and enhances its transcriptional activity (PubMed:15890677).
Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity (PubMed:12402037).
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 (PubMed:14645221).
Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity (PubMed:16617102).
Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity (PubMed:20955178).
Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902).
Acetylates MEF2D (PubMed:21030595).
Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degradation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990).
Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity).
Acetylates PCK1 and promotes PCK1 anaplerotic activity (PubMed:30193097).
Acetylates RXRA and RXRG (PubMed:17761950).
In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation or propionylation, respectively (PubMed:17267393, PubMed:25818647, PubMed:29775581, PubMed:31645732).
Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25818647).
Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low (PubMed:25818647).
Also acts as a histone butyryltransferase; butyrylation marks active promoters (PubMed:17267393).
Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription (PubMed:31645732).
Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes (PubMed:29775581).
Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493).
By similarity1 Publication30 Publications(Microbial infection) 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. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein.
2 PublicationsCatalytic activityi
- EC:2.3.1.485 PublicationsThis reaction proceeds in the forward1 Publication direction.
- 2-hydroxyisobutanoyl-CoA + L-lysyl-[protein] = CoA + H+ + N6-(2-hydroxyisobutanoyl)-L-lysyl-[protein]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 347 | Zinc 12 Publications | 1 | |
Metal bindingi | 351 | Zinc 12 Publications | 1 | |
Metal bindingi | 364 | Zinc 12 Publications | 1 | |
Metal bindingi | 369 | Zinc 12 Publications | 1 | |
Metal bindingi | 378 | Zinc 22 Publications | 1 | |
Metal bindingi | 382 | Zinc 22 Publications | 1 | |
Metal bindingi | 388 | Zinc 22 Publications | 1 | |
Metal bindingi | 393 | Zinc 22 Publications | 1 | |
Metal bindingi | 402 | Zinc 32 Publications | 1 | |
Metal bindingi | 406 | Zinc 32 Publications | 1 | |
Metal bindingi | 411 | Zinc 32 Publications | 1 | |
Metal bindingi | 414 | Zinc 32 Publications | 1 | |
Binding sitei | 1457 | Acetyl-CoA; via carbonyl oxygen1 Publication | 1 | |
Binding sitei | 1462 | Acetyl-CoA1 Publication | 1 | |
Binding sitei | 1466 | Acetyl-CoA1 Publication | 1 | |
Metal bindingi | 1670 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1673 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1683 | Zinc 5PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1686 | Zinc 5PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1692 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1695 | Zinc 4PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1701 | Zinc 5PROSITE-ProRule annotation | 1 | |
Metal bindingi | 1703 | Zinc 5PROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 331 – 417 | TAZ-type 1PROSITE-ProRule annotationAdd BLAST | 87 | |
Zinc fingeri | 1665 – 1713 | ZZ-typePROSITE-ProRule annotationAdd BLAST | 49 | |
Zinc fingeri | 1728 – 1809 | TAZ-type 2PROSITE-ProRule annotationAdd BLAST | 82 |
GO - Molecular functioni
- acetyltransferase activity Source: UniProtKB
- acyltransferase activity Source: UniProtKB
- androgen receptor binding Source: BHF-UCL
- beta-catenin binding Source: BHF-UCL
- chromatin binding Source: UniProtKB
- chromatin DNA binding Source: GO_Central
- damaged DNA binding Source: UniProtKB
- DNA binding Source: UniProtKB
- DNA-binding transcription factor binding Source: UniProtKB
- H3 histone acetyltransferase activity Source: GO_Central
- H4 histone acetyltransferase activity Source: GO_Central
- histone acetyltransferase activity Source: UniProtKB
- histone butyryltransferase activity Source: Ensembl
- histone crotonyltransferase activity Source: UniProtKB
- histone lactyltransferase activity Source: UniProtKB
- lysine N-acetyltransferase activity, acting on acetyl phosphate as donor Source: UniProtKB
- NF-kappaB binding Source: ARUK-UCL
- nuclear receptor binding Source: UniProtKB
- p53 binding Source: Ensembl
- peptide 2-hydroxyisobutyryltransferase activity Source: RHEA
- peptide butyryltransferase activity Source: UniProtKB
- peptide-lysine-N-acetyltransferase activity Source: Reactome
- peptide N-acetyltransferase activity Source: Reactome
- pre-mRNA intronic binding Source: Ensembl
- protein C-terminus binding Source: MGI
- protein propionyltransferase activity Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- STAT family protein binding Source: UniProtKB
- tau protein binding Source: ARUK-UCL
- transcription coactivator activity Source: UniProtKB
- transcription coactivator binding Source: UniProtKB
- transcription coregulator binding Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- animal organ morphogenesis Source: Ensembl
- apoptotic process Source: UniProtKB
- B cell differentiation Source: Ensembl
- behavioral defense response Source: Ensembl
- cell cycle Source: UniProtKB-KW
- cellular response to UV Source: UniProtKB
- circadian rhythm Source: UniProtKB
- epigenetic maintenance of chromatin in transcription-competent conformation Source: UniProtKB
- face morphogenesis Source: Ensembl
- fat cell differentiation Source: UniProtKB
- heart development Source: Ensembl
- histone acetylation Source: UniProtKB
- histone H2B acetylation Source: UniProtKB
- histone H3-K56 acetylation Source: Ensembl
- histone H4 acetylation Source: UniProtKB
- internal peptidyl-lysine acetylation Source: UniProtKB
- internal protein amino acid acetylation Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
- learning or memory Source: Ensembl
- lung development Source: Ensembl
- macrophage derived foam cell differentiation Source: UniProtKB
- megakaryocyte development Source: Ensembl
- multicellular organism growth Source: Ensembl
- negative regulation of gluconeogenesis Source: UniProtKB
- negative regulation of protein-containing complex assembly Source: ARUK-UCL
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- nervous system development Source: ARUK-UCL
- N-terminal peptidyl-lysine acetylation Source: UniProtKB
- peptidyl-lysine acetylation Source: ARUK-UCL
- peptidyl-lysine butyrylation Source: UniProtKB
- peptidyl-lysine crotonylation Source: UniProtKB
- peptidyl-lysine propionylation Source: UniProtKB
- platelet formation Source: Ensembl
- positive regulation by host of viral transcription Source: BHF-UCL
- positive regulation of DNA-binding transcription factor activity Source: UniProtKB
- positive regulation of neuron projection development Source: ARUK-UCL
- positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCL
- positive regulation of NIK/NF-kappaB signaling Source: ARUK-UCL
- positive regulation of protein binding Source: Ensembl
- positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding Source: ARUK-UCL
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: UniProtKB
- positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
- protein acetylation Source: UniProtKB
- protein destabilization Source: UniProtKB
- protein stabilization Source: UniProtKB
- regulation of androgen receptor signaling pathway Source: BHF-UCL
- regulation of autophagy Source: ParkinsonsUK-UCL
- regulation of cellular response to heat Source: Reactome
- regulation of glycolytic process Source: UniProtKB
- regulation of mitochondrion organization Source: UniProtKB
- regulation of signal transduction by p53 class mediator Source: Reactome
- regulation of tubulin deacetylation Source: UniProtKB
- response to estrogen Source: UniProtKB
- response to hypoxia Source: UniProtKB
- skeletal muscle tissue development Source: Ensembl
- somitogenesis Source: Ensembl
- stimulatory C-type lectin receptor signaling pathway Source: Reactome
- swimming Source: Ensembl
- thigmotaxis Source: Ensembl
Keywordsi
Molecular function | Acyltransferase, Transferase |
Biological process | Biological rhythms, Cell cycle, Host-virus interaction, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 2.3.1.48, 2681 |
PathwayCommonsi | Q09472 |
Reactomei | R-HSA-1234158, Regulation of gene expression by Hypoxia-inducible Factor R-HSA-1368082, RORA activates gene expression R-HSA-156711, Polo-like kinase mediated events R-HSA-1912408, Pre-NOTCH Transcription and Translation R-HSA-1989781, PPARA activates gene expression R-HSA-201722, Formation of the beta-catenin:TCF transactivating complex R-HSA-210744, Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells R-HSA-2122947, NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2197563, NOTCH2 intracellular domain regulates transcription R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-3134973, LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production R-HSA-3214847, HATs acetylate histones R-HSA-3371568, Attenuation phase R-HSA-381340, Transcriptional regulation of white adipocyte differentiation R-HSA-3899300, SUMOylation of transcription cofactors R-HSA-400253, Circadian Clock R-HSA-5250924, B-WICH complex positively regulates rRNA expression R-HSA-5617472, Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-5621575, CD209 (DC-SIGN) signaling R-HSA-5689901, Metalloprotease DUBs R-HSA-6781823, Formation of TC-NER Pre-Incision Complex R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6804114, TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest R-HSA-6804758, Regulation of TP53 Activity through Acetylation R-HSA-6804760, Regulation of TP53 Activity through Methylation R-HSA-6811555, PI5P Regulates TP53 Acetylation R-HSA-8866907, Activation of the TFAP2 (AP-2) family of transcription factors R-HSA-8936459, RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function R-HSA-8939243, RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known R-HSA-8941856, RUNX3 regulates NOTCH signaling R-HSA-8941858, Regulation of RUNX3 expression and activity R-HSA-8951936, RUNX3 regulates p14-ARF R-HSA-9013508, NOTCH3 Intracellular Domain Regulates Transcription R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription R-HSA-9018519, Estrogen-dependent gene expression R-HSA-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux R-HSA-9031628, NGF-stimulated transcription R-HSA-918233, TRAF3-dependent IRF activation pathway R-HSA-933541, TRAF6 mediated IRF7 activation R-HSA-9614657, FOXO-mediated transcription of cell death genes R-HSA-9616222, Transcriptional regulation of granulopoiesis R-HSA-9617629, Regulation of FOXO transcriptional activity by acetylation R-HSA-9701898, STAT3 nuclear events downstream of ALK signaling R-HSA-9707616, Heme signaling |
SignaLinki | Q09472 |
SIGNORi | Q09472 |
Protein family/group databases
MoonDBi | Q09472, Predicted |
Names & Taxonomyi
Protein namesi | Recommended name: Histone acetyltransferase p300 (EC:2.3.1.485 Publications)Short name: p300 HAT Alternative name(s): E1A-associated protein p300 Histone butyryltransferase p300 (EC:2.3.1.-1 Publication) Histone crotonyltransferase p300 (EC:2.3.1.-1 Publication) Protein 2-hydroxyisobutyryltransferase p300 (EC:2.3.1.-1 Publication) Protein lactyltransferas p300 (EC:2.3.1.-1 Publication) Protein propionyltransferase p300 (EC:2.3.1.-1 Publication) |
Gene namesi | Name:EP300 Synonyms:P300 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3373, EP300 |
MIMi | 602700, gene |
neXtProti | NX_Q09472 |
VEuPathDBi | HostDB:ENSG00000100393 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Nucleus
- Nucleus 6 Publications
Other locations
- Chromosome 2 Publications
Note: Localizes to active chromatin: Colocalizes with histone H3 acetylated and/or crotonylated at 'Lys-18' (H3K18ac and H3K18cr, respectively) (PubMed:25818647). In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Colocalizes with ROCK2 in the nucleus (PubMed:12929931).2 Publications
Cytosol
- cytosol Source: HPA
Nucleus
- histone acetyltransferase complex Source: GO_Central
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- chromosome Source: UniProtKB-SubCell
- protein-DNA complex Source: ARUK-UCL
- transcription regulator complex Source: GO_Central
Keywords - Cellular componenti
Chromosome, Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Rubinstein-Taybi syndrome 2 (RSTS2)1 Publication
Menke-Hennekam syndrome 2 (MKHK2)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081986 | 1824 | Q → P in MKHK2. 1 PublicationCorresponds to variant dbSNP:rs1569120903EnsemblClinVar. | 1 | |
Natural variantiVAR_081987 | 1831 | Missing in MKHK2. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 89 | S → A: Abolishes AMPK-mediated phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 89 | S → D: Phosphomimetic mutant that leads to descreased interaction with nuclear receptors. 1 Publication | 1 | |
Mutagenesisi | 344 | L → A: Inhibits interaction with HIF1A and transcription activation; when associated with A-345. 1 Publication | 1 | |
Mutagenesisi | 345 | L → A: Inhibits interaction with HIF1A and transcription activation; when associated with A-344. 1 Publication | 1 | |
Mutagenesisi | 371 – 376 | TMKNVL → NAAIRS: Inhibits interaction with HIF1A. Reduces interaction with CITED2. 1 Publication | 6 | |
Mutagenesisi | 413 – 418 | VCLPLK → NAAIRS: Inhibits interaction with HIF1A. Does not inhibit interaction with CITED2. 1 Publication | 6 | |
Mutagenesisi | 1020 | K → A: Abolishes sumoylation and transcriptional repression when associated with A-1024. 2 Publications | 1 | |
Mutagenesisi | 1020 | K → R: Abolishes sumoylation and transcriptional repression; when associated with R-1024. 2 Publications | 1 | |
Mutagenesisi | 1024 | K → A: Abolishes sumoylation and transcriptional repression; when associated with A-1020. 2 Publications | 1 | |
Mutagenesisi | 1024 | K → R: Abolishes sumoylation and transcriptional repression; when associated with R-1020. 2 Publications | 1 | |
Mutagenesisi | 1170 | F → E: Increased acetyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1204 | C → R: Increased acetyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1242 | E → K: Increased acetyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1357 | T → L: 40% decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 1357 | T → R: 40% decrease in activity. 90% decrease in activity; when associated with R-1505; R-1625 and R-1628. 1 Publication | 1 | |
Mutagenesisi | 1396 | S → R: Loss of activity; when associated with R-1397. 1 Publication | 1 | |
Mutagenesisi | 1396 | S → W: Loss of activity; when associated with W-1396. 1 Publication | 1 | |
Mutagenesisi | 1397 | Y → R: Loss of activity; when associated with R-1396. 1 Publication | 1 | |
Mutagenesisi | 1397 | Y → W: Loss of activity; when associated with W-1397. 1 Publication | 1 | |
Mutagenesisi | 1399 | D → Y: Abolished acetyltransferase and acyltransferase activities. Abolishes autoacetylation. Does not interact with TFAP2A and inhibits transcriptional coactivation of TFAP2A by CITED2. Does not inhibit interaction with CITED2, DNA-binding of TFAP2A or nuclear localization of TFAP2A or CITED2. No enhancement of FOXO1-mediated transcriptional activity. No inhibition of insulin-mediated translocation to the cytoplasm. No acetylation of RXRA. 5 Publications | 1 | |
Mutagenesisi | 1467 | Y → F: Abolishes autoacetylation. Loss of acetyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1504 | F → A: Abolished acetyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1505 | E → R: 90% decrease in activity; when associated with R-1625 and R-1628. 90% decrease in activity; when associated with R-1357; R-1625 and R-1628. 1 Publication | 1 | |
Mutagenesisi | 1625 | D → R: 70% decrease in activity; when associated with R-1628. 90% decrease in activity; when associated with R-1505 and R-1628. 90% decrease in activity; when associated with R-1357; R-1505 and R-1628. 1 Publication | 1 | |
Mutagenesisi | 1628 | D → R: 70% decrease in activity; when associated with R-1625. 90% decrease in activity; when associated with E-1505 and R-1625. 90% decrease in activity; when associated with R-1357; R-1505 and R-1625. 1 Publication | 1 | |
Mutagenesisi | 1645 – 1646 | RR → EE: Increased acetyltransferase activity. 1 Publication | 2 | |
Mutagenesisi | 2056 | R → K: No effect on interaction with NCOA2. 1 Publication | 1 | |
Mutagenesisi | 2088 | R → K: Abolishes interaction with NCOA2. 1 Publication | 1 | |
Mutagenesisi | 2142 | R → K: Strongly reduces interaction with NCOA2. 1 Publication | 1 |
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 31 – 32 | Breakpoint for translocation to form KAT6A-EP300 and EP300-KAT6A | 2 |
Keywords - Diseasei
Disease variant, Mental retardationOrganism-specific databases
DisGeNETi | 2033 |
GeneReviewsi | EP300 |
MalaCardsi | EP300 |
MIMi | 613684, phenotype 618333, phenotype |
OpenTargetsi | ENSG00000100393 |
Orphaneti | 353284, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency |
PharmGKBi | PA27807 |
Miscellaneous databases
Pharosi | Q09472, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3784 |
GuidetoPHARMACOLOGYi | 2735 |
Genetic variation databases
BioMutai | EP300 |
DMDMi | 223590203 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000211193 | 2 – 2414 | Histone acetyltransferase p300Add BLAST | 2413 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 89 | Phosphoserine; by AMPK2 Publications | 1 | |
Modified residuei | 418 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 423 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 499 | PhosphoserineBy similarity | 1 | |
Modified residuei | 580 | Asymmetric dimethylarginine; by CARM11 Publication | 1 | |
Modified residuei | 604 | Asymmetric dimethylarginine; by CARM11 Publication | 1 | |
Modified residuei | 636 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 977 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 1020 | N6-acetyllysine; alternate1 Publication | 1 | |
Cross-linki | 1020 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
Modified residuei | 1024 | N6-acetyllysine; alternate1 Publication | 1 | |
Cross-linki | 1024 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
Modified residuei | 1038 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1180 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 1336 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 1473 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 1499 | N6-acetyllysine; by autocatalysis1 Publication | 1 | |
Modified residuei | 1542 | N6-acetyllysineCombined sources1 Publication | 1 | |
Modified residuei | 1546 | N6-acetyllysineCombined sources1 Publication | 1 | |
Modified residuei | 1549 | N6-acetyllysine; by autocatalysis2 Publications | 1 | |
Modified residuei | 1554 | N6-acetyllysine; by autocatalysisCombined sources1 Publication | 1 | |
Modified residuei | 1555 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 1558 | N6-acetyllysineCombined sources1 Publication | 1 | |
Modified residuei | 1560 | N6-acetyllysine; by autocatalysisCombined sources1 Publication | 1 | |
Modified residuei | 1583 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 1699 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 1704 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 1707 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 1726 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2142 | Asymmetric dimethylarginine; by CARM1; alternate1 Publication | 1 | |
Modified residuei | 2142 | Citrulline; by PADI4; alternate1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Citrullination, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-1240 |
EPDi | Q09472 |
jPOSTi | Q09472 |
MassIVEi | Q09472 |
MaxQBi | Q09472 |
PaxDbi | Q09472 |
PeptideAtlasi | Q09472 |
PRIDEi | Q09472 |
ProteomicsDBi | 58723 |
PTM databases
GlyGeni | Q09472, 3 sites, 1 O-linked glycan (3 sites) |
iPTMneti | Q09472 |
MetOSitei | Q09472 |
PhosphoSitePlusi | Q09472 |
Expressioni
Gene expression databases
Bgeei | ENSG00000100393, Expressed in kidney and 243 other tissues |
ExpressionAtlasi | Q09472, baseline and differential |
Genevisiblei | Q09472, HS |
Organism-specific databases
HPAi | ENSG00000100393, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with HIF1A; the interaction is stimulated in response to hypoxia and inhibited by CITED2 (PubMed:9887100, PubMed:11959990). Probably part of a complex with HIF1A and CREBBP (PubMed:8917528).
Interacts (via N-terminus) with TFAP2A (via N-terminus); the interaction requires CITED2 (PubMed:12586840).
Interacts (via CH1 domain) with CITED2 (via C-terminus) (PubMed:12586840, PubMed:12778114).
Interacts with CITED1 (unphosphorylated form preferentially and via C-terminus) (PubMed:10722728, PubMed:16864582).
Interacts with ESR1; the interaction is estrogen-dependent and enhanced by CITED1 (PubMed:11581164).
Interacts with HIPK2 (By similarity).
Interacts with DTX1, EID1, ELF3, FEN1, LEF1, NCOA1, NCOA6, NR3C1, PCAF, PELP1, PRDM6, SP1, SP3, SPIB, SRY, TCF7L2, DDX5, DDX17, SATB1, SRCAP and TRERF1 (PubMed:11073989, PubMed:11073990, PubMed:10823961, PubMed:11349124, PubMed:11430825, PubMed:11481323, PubMed:11564735, PubMed:11581372, PubMed:11864910, PubMed:12446687, PubMed:12527917, PubMed:12837748, PubMed:14605447, PubMed:15075319, PubMed:15297880, PubMed:16478997, PubMed:8684459, PubMed:17226766, PubMed:9590696).
Interacts with JMY, the complex activates p53/TP53 transcriptional activity (PubMed:10518217, PubMed:11511361).
Interacts with TTC5/STRAP; the interaction facilitates the association between JMY and p300/EP300 cofactors (PubMed:11511361).
Interacts with p53/TP53; the interation is facilitated by TTC5/STRAP (PubMed:15186775, PubMed:15448695, PubMed:19217391).
Forms a complex with TTC5/STRAP and HSF1; these interactions augment chromatin-bound HSF1 and p300/EP300 histone acetyltransferase activity (PubMed:18451878).
Part of a complex containing CARM1 and NCOA2/GRIP1 (PubMed:11701890, PubMed:11997499, PubMed:15731352).
Interacts with ING4 and this interaction may be indirect (PubMed:12750254).
Interacts with ING5 (PubMed:12750254).
Interacts with the C-terminal region of CITED4 (PubMed:11744733). Non-sumoylated EP300 preferentially interacts with SENP3 (PubMed:19680224).
Interacts with SS18L1/CREST (PubMed:14716005).
Interacts with ALX1 (via homeobox domain) (PubMed:12929931).
Interacts with NEUROD1; the interaction is inhibited by NR0B2 (PubMed:14752053).
Interacts with TCF3 (PubMed:14752053).
Interacts (via CREB-binding domain) with MYOCD (via C-terminus) (By similarity).
Interacts with ROCK2 and PPARG (PubMed:11518699, PubMed:16574662).
Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes (PubMed:20081228).
Interacts with IRF1 and this interaction enhances acetylation of p53/TP53 and stimulation of its activity (PubMed:15509808).
Interacts with FOXO1; the interaction acetylates FOXO1 and enhances its transcriptional activity (PubMed:15890677).
Interacts with ALKBH4 and DDIT3/CHOP (PubMed:17872950, PubMed:23145062).
Interacts with KLF15 (PubMed:23999430).
Interacts with CEBPB and RORA (PubMed:9862959).
Interacts with NPAS2, ARNTL/BMAL1 and CLOCK (PubMed:14645221).
Interacts with SIRT2 isoform 1, isoform 2 and isoform 5 (PubMed:24177535).
Interacts with MTA1 (PubMed:16617102).
Interacts with HDAC4 and HDAC5 in the presence of TFAP2C (PubMed:24413532).
Interacts with TRIP4 (PubMed:25219498). Directly interacts with ZBTB49; this interaction leads to synergistic transactivation of CDKN1A (PubMed:25245946).
Interacts with NR4A3 (By similarity).
Interacts with ZNF451 (PubMed:24324267).
Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding (By similarity).
Interacts with HSF1 (PubMed:27189267).
Interacts with ZBTB48/TZAP (PubMed:24382891).
Interacts with STAT1; the interaction is enhanced upon IFN-gamma stimulation (PubMed:26479788).
Interacts with HNRNPU (via C-terminus); this interaction enhances DNA-binding of HNRNPU to nuclear scaffold/matrix attachment region (S/MAR) elements (PubMed:11909954).
Interacts with BCL11B (PubMed:27959755, PubMed:16809611).
Interacts with SMAD4; negatively regulated by ZBTB7A (PubMed:25514493).
Interacts with DUX4 (via C-terminus) (PubMed:26951377).
Interacts with NUPR1; this interaction enhances the effect of EP300 on PAX2 transcription factor activity (PubMed:11940591).
Interacts with RXRA; the interaction is decreased by 9-cis retinoic acid (PubMed:17761950). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950).
Interacts with RB1 (By similarity).
Interacts with DDX3X; this interaction may facilitate HNF4A acetylation (PubMed:28128295).
Interacts with SOX9 (PubMed:12732631).
Interacts with ATF4; EP300/p300 stabilizes ATF4 and increases its transcriptional activity independently of its catalytic activity by preventing its ubiquitination (PubMed:16219772).
Interacts with KAT5; promoting KAT5 autoacetylation (PubMed:24835996).
By similarity71 Publications(Microbial infection) Interacts with human adenovirus 5 E1A protein; this interaction stimulates the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-protein complex.
1 Publication(Microbial infection) Interacts with and acetylates HIV-1 Tat.
3 Publications(Microbial infection) Interacts with HTLV-1 proteins Tax, p30II and HBZ.
3 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 2088 | Interaction with NCOA2 | 1 | |
Sitei | 2142 | Interaction with NCOA2 | 1 |
Binary interactionsi
Q09472
GO - Molecular functioni
- androgen receptor binding Source: BHF-UCL
- beta-catenin binding Source: BHF-UCL
- DNA-binding transcription factor binding Source: UniProtKB
- NF-kappaB binding Source: ARUK-UCL
- nuclear receptor binding Source: UniProtKB
- p53 binding Source: Ensembl
- protein C-terminus binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- STAT family protein binding Source: UniProtKB
- tau protein binding Source: ARUK-UCL
- transcription coactivator binding Source: UniProtKB
- transcription coregulator binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 108347, 760 interactors |
CORUMi | Q09472 |
DIPi | DIP-257N |
IntActi | Q09472, 205 interactors |
MINTi | Q09472 |
STRINGi | 9606.ENSP00000263253 |
Chemistry databases
BindingDBi | Q09472 |
Miscellaneous databases
RNActi | Q09472, protein |