Summary

Name EP300
Full Name Histone acetyltransferase p300
Synonyms p300 HAT, E1A-associated protein p300 | P300
Primary ID Q09472
Links - -
Type protein
Relations 85
Pathways Acute Myeloid Leukemia, FLT3 in AML, COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS, T-Lymphocyte: IL6, T-Lymphocyte: TGF beta
Function 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 TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (PubMed:18722353). 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 degragation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990). Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity). 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). Acetylates PCK1 and promotes PCK1 anaplerotic activity (PubMed:30193097). Acetylates RXRA and RXRG (PubMed:17761950).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png deacetylation EP300 0.829
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates img/direct-activation.png acetylation KPNA2 0.363
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png acetylation H3-3A 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png acetylation RELA 0.814
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates img/direct-activation.png acetylation TP53 0.909
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ up-regulates quantity by stabilization img/direct-activation.png acetylation SMAD3 0.726
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS
+ up-regulates img/direct-activation.png acetylation DUSP1 0.315
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png acetylation PCK1 0.526
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png acetylation SMAD7 0.476
Publications: 4 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation EP300 0.413
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation EP300 0.2
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML, COVID-19 Causal Network
+ up-regulates img/direct-activation.png phosphorylation EP300 0.411
Publications: 1 Organism: Homo Sapiens
Pathways:p53 in cancer
+ up-regulates img/direct-activation.png phosphorylation EP300 0.333
Publications: 2 Organism: Homo Sapiens
Tissue: Muscle
+ up-regulates img/direct-activation.png phosphorylation EP300 0.685
Publications: 2 Organism: Homo Sapiens
Tissue: Muscle
Pathways:IGF and Myogenesis
+ up-regulates img/direct-activation.png phosphorylation EP300 0.2
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML, COVID-19 Causal Network
+ up-regulates img/direct-activation.png phosphorylation EP300 0.2
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML, COVID-19 Causal Network
+ up-regulates img/direct-activation.png phosphorylation EP300 0.478
Publications: 3 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation EP300 0.374
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation EP300 0.384
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation EP300 0.255
Publications: 1
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TBXAS1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding SMAD1 0.414
Publications: 2 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CPT1B 0.2
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png binding EP300 0.327
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png deubiquitination EP300 0.275
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png acetylation Histone H3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MEF2A 0.855
Publications: 1 Organism: Homo Sapiens
Pathways:IGF and Myogenesis
+ up-regulates img/direct-activation.png binding EP300 0.389
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation KRT16 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding EP300 0.348
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png acetylation TP53 0.909
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ up-regulates img/direct-activation.png binding FLI1 0.296
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding CDX2/PAX6/P300 0.458
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/direct-activation.png acetylation RUNX2 0.464
Publications: 2 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination TP53 0.909
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ up-regulates activity img/direct-activation.png binding EP300 0.322
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EP300 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding EP300 0.347
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MEF2C 0.73
Publications: 2 Organism: Homo Sapiens
Pathways:IGF and Myogenesis
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination EP300 0.473
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png acetylation EP300 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML, COVID-19 Causal Network, Fibrosis, IGF and Myogenesis, p53 in cancer, SARS-CoV FIBROSIS
+ up-regulates img/direct-activation.png binding, relocalization EP300 0.635
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding EP300 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MN1 0.348
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png acetylation MAML1 0.635
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png acetylation XBP1 (isoform 2) 0.289
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network
+ up-regulates img/direct-activation.png acetylation MYOD1 0.667
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle
Pathways:IGF and Myogenesis
+ up-regulates img/direct-activation.png acetylation PLAGL2 0.2
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding RUNX2/EP300 0.464
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates img/direct-activation.png acetylation RELA 0.814
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates img/direct-activation.png binding MEF2D 0.732
Publications: 1 Organism: Homo Sapiens
Pathways:IGF and Myogenesis
+ up-regulates img/direct-activation.png acetylation PLAG1 0.314
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding EP300 0.693
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation ALOX15 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png Differentiation 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3 in AML
+ form complex img/form-complex.png binding P300/PCAF 0.654
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding EP300 0.544
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding EP300 0.431
Publications: 2
+ up-regulates activity img/direct-activation.png binding EP300 0.436
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EP300 0.675
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CAV3 0.2
Publications: 1 Organism: Chlorocebus Aethiops
+ form complex img/form-complex.png binding SMAD2/STAT3/EP300 0.674
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination EP300 0.37
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding CBP/p300 0.524
Publications: 1 Organism: Homo Sapiens