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FLASH GENE
Symbol EP300 contributors: mct/npt/pgu - updated : 24-01-2013
HGNC name E1A binding protein p300
HGNC id 3373
Corresponding disease
RSTS2 Rubinstein-Taybi syndrome 2
Location 22q13.2      Physical location : 41.488.613 - 41.576.080
Synonym name
  • histone acetyltransferase p300
  • E1A-binding protein, 300kD
  • p300 HAT
  • Synonym symbol(s) CREBBPM, E1ABP, P300, CBP/P300, KAT3B, RSTS2
    EC.number 2.3.1.48
    DNA
    TYPE functioning gene
    STRUCTURE 87.47 kb     31 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    KIAA1093 22q13.1 N-acetylgalactosaminidase, alpha- ADSL 22q13.1 adenylosuccinate lyase DJ1042K10.2 22q13.1-q13.2 hypothetical protein DJ1042K10.2 MKL1 22q13 megakaryoblastic leukemia (translocation) 1 LOC391333 22 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) GPR24 22q13.3 G protein-coupled receptor 24 SLC25A17 22q13.2 solute carrier family 25 (mitochondrial carrier; peroxisomal membrane protein, 34kDa), member 17 ST13 22q13 suppression of tumorigenicity 13 (colon carcinoma) (Hsp70 interacting protein) LOC63929 22q13.31-q13.33 hypothetical protein LOC63929 DNAJB7 22q13.2 DnaJ (Hsp40) homolog, subfamily B, member 7 RBX1 22q13.1 ring-box 1 RPS9P2 22q13.2 ribosomal protein S9 pseudogene 2 LOC391334 22 similar to mutant beta-actin (beta-actin) EP300 22q13.2 E1A binding protein p300 LOC391335 22 similar to KIAA0563 protein L3MBTL2 22q13.31-q13.33 l(3)mbt-like 2 (Drosophila) RANGAP1 22q13.1 Ran GTPase activating protein 1 RoXaN 22q13.2 ubiquitous tetratricopeptide containing protein RoXaN TEF 22q13.1 thyrotrophic embryonic factor TOB2 22q13.2 transducer of ERBB2, 2 PHF5A 22q13.3 PHD finger protein 5A ACO2 22q13.1 aconitase 2, mitochondrial RPC8 22q13.2 RNA polymerase III subunit RPC8 PIPPIN 22q13.2-q13.31 RNA-binding protein pippin PMM1 22q13.2 phosphomannomutase 1 D15Wsu75e 22q13.2 DNA segment, Chr 15, Wayne State University 75, expressed G22P1 22q13.1 thyroid autoantigen 70kDa (Ku antigen) NHP2L1 22q13.2-q13.1 NHP2 non-histone chromosome protein 2-like 1 (S. cerevisiae) FLJ23584 22q13.2 hypothetical protein FLJ23584 HMG17L2 22q13.2 high-mobility group (nonhistone chromosomal) protein 17-like 2 MGC40042 22q13.2 hypothetical protein MGC40042 FLJ22349 22q13.2 hypothetical protein FLJ22349 SREBF2 22q13.2 sterol regulatory element binding transcription factor 2 TNFRSF13C 22q13.1-q13.31 tumor necrosis factor receptor superfamily, member 13C C22orf18 22q13.2-q13.31 chromosome 22 open reading frame 18 SEPT3 22q13.2 septin 3 MGC26816 22q13.31 hypothetical protein MGC26816 NAGA 22q13.2 N-acetylgalactosaminidase, alpha-
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    31 - 8761 - 2414 - 2009 19539243
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
    Endocrineparathyroid   highly
     thyroid   highly
    Lymphoid/Immunelymph node   highly
    Nervousnervecranial nerve  moderately
    Reproductivefemale systembreastmammary gland moderately
    Respiratoryrespiratory tractlarynx  predominantly
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text embryonic tissue, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal nuclear receptor interaction motif (LXXLL)
  • three cysteine-histidine rich (C4-H-C3), TAZ, PHD type zinc finger motifs with a CREB (cAMP response element binding protein)
  • a bromodomain between C/H1 and C/H2
  • a KIX domain interacting with FOXO3
  • ZZ zinc finger motif
  • HOMOLOGY
    interspecies homolog to rattus Ep300 (94.30 pc)
    homolog to murine Ep300 (94.26 pc)
    intraspecies homolog to CREBBP
    Homologene
    FAMILY
    CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,kinetochore
    basic FUNCTION
  • chromatin assembly and transcription activation
  • target of adenoviral E1A oncoprotein,structurally and putatively preventing the G0/G1 transition in cell cycle
  • acting as an histone acetyltransferase for the four core histones in nucleosome
  • acetylating and activating TP53 after DNA damage and participating in chromatin remodeling
  • stimulating hypoxia-induced genes such as VEGF
  • involved in DNA repair synthesis
  • regulating acetylation of FEN1
  • coregulating with NCOA1 of the STAT3 transcriptional activity
  • modulating the BRCA1 inhibition of estrogen receptor activity
  • complex CBP/p300 function as co-activators of SOX9 for cartilage tissue-specific gene expression and chondrocyte differentiation
  • playing a crucial role in mediating the functional synergism between PAX8 and TTF-1 in thyroid-specific gene expression
  • activating Sox9-dependent transcription during chondrogenesis
  • can inactivate SIRT2 by acetylation and may regulate the activity of TP53 indirectly through SIRT2 in addition to its direct modification of TP53
  • overexpression of EP300 upregulated PTTG1 at the levels of promoter activity, mRNA and protein expression
  • CREBBP and EP300 function as transcriptional coactivators for a large number of DNA-binding transcription factors involved in multiple signalling and developmental pathways, by modifying lysine residues on both histone and non-histone nuclear proteins
  • may regulate the activity of Sp1 indirectly through HDAC6 in addition to its direct modification of Sp1
  • playing an important role in maintaining genomic integrity by negatively regulating c-myc
  • can regulate NBN-mediated DNA damage response, and these events occur in an acetylation-dependent manner
  • implicated in the acetylation of SPHK1 at a conserved acetylation motif (the GK motif)
  • involved in acetylation of SKP2, which is a process that can be antagonized by the SIRT3 deacetylase
  • CELLULAR PROCESS cell cycle
    nucleotide, repair
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    CDKN1A-EP300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division
    a component
  • component with CREBBP of a coactivator complex connecting the basal transcriptional machinery to various DNA binding factors
  • component of a ternary complex with TP53 and MDM2
  • binding a complex between MADH1 and STAT3,involved in the cooperative signaling of LIF and BMP2
  • component with CREBBP and IRF3 of the double strand RNA-activated factor DRAF1
  • central role for the ATF5/EP300 complex in ATF5 function, suggesting that coordinated actions by ATF5, EP300, ELK1, and ERK/mitogen-activated protein kinase (MAPK) are essential for ATF5-dependent EGR1 activation and cell proliferation and survival
  • INTERACTION
    DNA
  • binding to the promoter of FTH1 (contributing to its tissue specific expression)
  • binding to scaffold/matrix attachment region (S/MAR) element
  • RNA
    small molecule
    protein
  • PAX8 (coactivator of PAX8)
  • binding to HIF1A (coactivation of)
  • binding to PCNA
  • interacting with SIRT2 (triggers the acetylation and subsequent down-regulation of the deacetylation activity of SIRT2, andacetylation of SIRT2 by EP300 relieves the inhibitory effect of SIRT2 on the transcriptional activity of TP53)
  • binding to S/MAR binding protein scaffold attachment factor A (SAF-A)
  • binding to STAT3 and SMAD1
  • SNIP1
  • by its histone acetyltransferase activity, involved in regulation of WT1 transcription
  • transcriptional coactivator p300 may regulate fibronectin expression via PARP and NF-kappaB activation in diabetes
  • interacting PML
  • interacting with EP300 and HDAC1 (acetylation of NR4A1 is modulated by EP300 and HDAC1, suggesting that acetylation is an important post-translational modification for the rapid turnover of NR4A1 protein)
  • MAGEA11 links N-terminal domains of AR and EP300 to promote transcriptional synergy through a cadre of FXXLF-related interacting motifs
  • interacts with the C terminus of PAX5 and acetylates multiple lysine residues within the paired box DNA binding domain of PAX5
  • interacting with HDAC9 (induction of adipogenic differentiation promotes HDAC9 down-regulation and replacement by EP300 at the E-box site of the CEBPA gene promoter, thus switching on adipogenic gene expression)
  • EP300 and SIRT1 were recruited to histone gene promoters in an NPAT-dependent manner
  • ATF3 decreases the interaction of EP300 with PDX1
  • interactions between FOXO3 and the EP300 KIX domain
  • TCF3 and EP300 act in synergy to promote chromatin accessibility of the immunoglobulin &
  • 954; locus
  • chromatin regulators EP300, KDM5A, KDM6A and KDM6B cooperate with KLF4 in promoting the transcription of POU5F1
  • SETD1A, SETD1B and EP300 act cooperatively, through direct interactions and coupled histone modifications, to facilitate the function of TP53
  • KDM1A cooperates with EP300 to facilitate ESR1 protein acetylation and target gene activation upon estrogen stimulation
  • binds to and acetylates MTA2 to promote colorectal cancer cells growth
  • EP300 negatively regulates ATAT1 expression and is sequestered on microtubules upon stress
  • cell & other
    REGULATION
    inhibited by the adenovirus oncoprotein E1A
    NAP1L1, binding to the KIX domain
    ASSOCIATED DISORDERS
    corresponding disease(s) RSTS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    translocation t (11;22)(q23;q13) in acute myeloid leukemia
    tumoral fusion      
    in acute monocytic leukemia with t(8;22) (p11;q13) (fusion with MYST3)
    tumoral somatic mutation      
    in epithelial cancer
    tumoral fusion      
    fusion genes MYST3-EP300, in acute myeloid leukemia (AML) by chromosomal translocation
    tumoral somatic mutation     loss of function
    in B-cell non-Hodgkin lymphoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    use of histone deacetylase inhibitors has a potential therapy in B-cell non-Hodgkin lymphoma
    cancerhemopathy 
    inhibition of EP300 abrogates the acetylation of RUNX1-RUNX1T1 and impairs its ability to promote leukemic transformation, and represent a potential therapeutic target in AML
    ANIMAL & CELL MODELS