SUBUNIT: Interacts with phosphorylated CREB1 (By similarity). Interacts with HIF1A; the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts (via N-terminus) with TFAP2A (via N-terminus); the interaction requires CITED2. Interacts (via CH1 domain) with CITED2 (via C-terminus). Interacts with CITED1 (unphosphorylated form preferentially and via C- terminus). Interacts with ESR1; the interaction is estrogen- dependent and enhanced by CITED1. Interacts with DTX1, EID1, ELF3, FEN1, LEF1, NCOA1, NCOA6, NR3C1, PCAF, PELP1, PRDM6, SP1, SP3, SPIB, SRY, TCF7L2, TP53, SATB1, SRCAP, TTC5, JMY and TRERF1. The TAZ-type 1 domain interacts with HIF1A. Probably part of a complex with HIF1A and CREBBP. Part of a complex containing CARM1 and NCOA2/GRIP1. Interacts with ING4 and this interaction may be indirect. Interacts with ING5. Interacts with the C-terminal region of CITED4. Interacts with HTLV-1 Tax and p30II. Interacts with and acetylates HIV-1 Tat. Non-sumoylated EP300 preferentially interacts with SENP3. Interacts with SS18L1/CREST. Interacts with ALX1 (via homeobox domain). Interacts with NEUROD1; the interaction is inhibited by NR0B2. Interacts with TCF3. Interacts (via CREB-binding domain) with MYOCD (via C-terminus) (By similarity). Binds to HIPK2 (By similarity). Interacts with ROCK2.

SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Co-localizes with ROCK2 in the nucleus.

PTM: Acetylated on Lys at up to 17 positions by intermolecular autocatalysis.

PTM: Citrullinated at Arg-2142 by PADI4, which impairs methylation by CARM1 and promotes interaction with NCOA2/GRIP1.

PTM: Methylated at Arg-580 and Arg-604 in the KIX domain by CARM1, which blocks association with CREB, inhibits CREB signaling and activates apoptotic response. Also methylated at Arg-2142 by CARM1, which impairs interaction with NCOA2/GRIP1.

PTM: Sumoylated; Desumoylated by SENP3 through the removal of SUMO2 and SUMO3.

PTM: Probable target of ubiquitination by FBXO3, leading to rapid proteasome-dependent degradation.

PTM: Phosphorylated by HIPK2 in a RUNX1-dependent manner. This phosphorylation that activates EP300 happens when RUNX1 is associated with DNA and CBFB. Phosphorylated by ROCK2 and this enhances its activity.

DISEASE: Note=Defects in EP300 may play a role in epithelial cancer.

DISEASE: Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with MYST3.

DISEASE: Defects in EP300 are the cause of Rubinstein-Taybi syndrome type 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.

SIMILARITY: Contains 1 bromo domain.

SIMILARITY: Contains 1 KIX domain.

SIMILARITY: Contains 2 TAZ-type zinc fingers.

SIMILARITY: Contains 1 ZZ-type zinc finger. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/P300ID97.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/EP300"; WEB RESOURCE: Name=Wikipedia; Note=P300/CBP entry; URL="http://en.wikipedia.org/wiki/P300/CBP";

GENE SYNONYMS: P300.

COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.