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histone acetyltransferase p300; p300 HAT; E1A-associated protein p300 (EP300, P300)

Function: - functions as histone acetyltransferase - regulates transcription via chromatin remodeling - acetylates all 4 core histones in nucleosomes - histone acetylation gives an epigenetic tag for transcriptional activation - mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein - acetylated on Lys at up to 17 positions by intermolecular autocatalysis - citrullinated at Arg-2142 by PADI4, which impairs methylation by CARM1 & promotes interaction with NCOA2/GRIP1 - methylated at Arg-580 & Arg-604 in the KIX domain by CARM1, which blocks association with CREB, inhibits CREB signaling & activates apoptotic response - also methylated at Arg-2142 by CARM1, which impairs interaction with NCOA2/GRIP1 - phosphorylated - interacts with phosphorylated CREB1 (putative) - interacts with DTX1, EID1, ELF3, FEN1, LEF1, NCOA1, NCOA6, NR3C1, PCAF, PELP1, PRDM6, SPIB, SRY, TCF7L2, TP53, SRCAP, TTC5, JMY & TRERF1 - the TAZ-type 1 domain interacts with HIF1A - probably part of a complex with HIF1A & CREBBP - part of a complex containing CARM1 & NCOA2/GRIP1 - interacts with ING4 & this interaction may be indirect - interacts with ING5 - interacts with the C-terminal region of CITED4 - interacts with HTLV-1 Tax & p30II - interacts with & acetylates HIV-1 Tat Structure: - contains 1 bromo domain - contains 1 KIX domain - contains 2 TAZ-type Zn+2 fingers - contains 1 ZZ-type Zn+2 finger Compartment: nucleus Pathology: - defects in EP300 may play a role in epithelial cancer - chromosomal translocation t(8;22)(p11;q13) involving EP300 with MYST3 may be a cause of acute myeloid leukemias - binds to & may be involved in the transforming capacity of the adenovirus E1A protein - in case of HIV-1 infection, EP300 is recruited by the viral protein Tat; regulates Tat's transactivating activity & may help inducing chromatin remodeling of proviral genes - defects in EP300 are a cause of Rubinstein-Taybi syndrome

Interactions

molecular events

Related

CREB-binding protein; CBP transcriptional coactivator (CREBBP, CBP)

General

transcriptional adaptor protein; transcriptional coactivator zinc finger protein

Properties

SIZE: entity length = 2414 aa MW = 264 kD COMPARTMENT: cell nucleus MOTIF: nuclear translocation signal {11-17} breakpoint {31-32} Zinc finger NAME: Zinc finger SITE: 331-417 EFFECTOR-BOUND: Zn+2 KIX {566-645} serine-rich region {797-800} MOTIF: serine residue (SEVERAL) bromodomain {1067-1139} glutamate-rich region {1519-1526} MOTIF: glutamate residue (SEVERAL) Binding region for E1A adenovirus {1572-1818} MOTIF: Zn finger ZZ-type NAME: Zn finger ZZ-type SITE: 1664-1707 EFFECTOR-BOUND: Zn+2 Zinc finger NAME: Zinc finger SITE: 1728-1809 EFFECTOR-BOUND: Zn+2 HTLV-1 Tax interaction {2003-2212} NCOA2 interaction {2041-2240} MOTIF: glutamine-rich region {2066-2069} MOTIF: glutamine residue (SEVERAL) arginine residue {2088} arginine residue {2142} glutamine-rich region {2190-2195} MOTIF: glutamine residue (SEVERAL)

References

  1. Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature. 1995 Mar 2;374(6517):81-4. PMID: 7870178 1995
  2. Lundblad JR, Kwok RP, Laurance ME, Harter ML, Goodman RH. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature. 1995 Mar 2;374(6517):85-8. PMID: 7870179 1995
  3. Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K. Recruitment of p300/CBP in p53-dependent signal pathways. Cell. 1997 Jun 27;89(7):1175-84. PMID: 9215639
  4. UniProt :accession Q09472
  5. Entrez Gene :accession 2033
  6. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/P300ID97.html
  7. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=EP300
  8. Wikipedia; Note: P300/CBP entry http://en.wikipedia.org/wiki/P300/CBP

Component-of

molecular complex

Databases & Figures

OMIM correlations MORBIDMAP 602700 UniProt Q09472 PFAM correlations Entrez Gene 2033 ENZYME 2.3.1.48 HIF-1 pathway