histone acetyltransferase p300; p300 HAT; E1A-associated protein p300 (EP300, P300)
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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
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
More general terms
Additional terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/7870178 1995
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/7870179 1995
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/9215639
- ↑ UniProt http://www.uniprot.org/uniprot/Q09472.html
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2033
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/P300ID97.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=EP300
- ↑ Wikipedia; Note: P300/CBP entry http://en.wikipedia.org/wiki/P300/CBP