Human Gene EP300 (ENST00000263253.9) Description and Page Index
Description: Homo sapiens E1A binding protein p300 (EP300), transcript variant 1, mRNA. (from RefSeq NM_001429) RefSeq Summary (NM_001429): This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000263253.9 Gencode Gene: ENSG00000100393.14 Transcript (Including UTRs) Position: hg38 chr22:41,092,592-41,180,077 Size: 87,486 Total Exon Count: 31 Strand: + Coding Region Position: hg38 chr22:41,093,005-41,178,956 Size: 85,952 Coding Exon Count: 31
ID:EP300_HUMAN DESCRIPTION: RecName: Full=Histone acetyltransferase p300; Short=p300 HAT; EC=220.127.116.11; AltName: Full=E1A-associated protein p300; FUNCTION: Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. 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. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity. CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl- [histone]. 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, DDX5, DDX17, 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 and PPARG. Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes. Interacts with IRF1 and this interaction enhances acetylation of p53/TP53 and stimulation of its activity. Interacts with FOXO1; the interaction acetylates FOXO1 and enhances its transcriptional activity. Interacts with DDIT3/CHOP. INTERACTION: P27695:APEX1; NbExp=6; IntAct=EBI-447295, EBI-1048805; Q9NPI1:BRD7; NbExp=3; IntAct=EBI-447295, EBI-711221; Q99967:CITED2; NbExp=3; IntAct=EBI-447295, EBI-937732; P17844:DDX5; NbExp=4; IntAct=EBI-447295, EBI-351962; Q16665:HIF1A; NbExp=5; IntAct=EBI-447295, EBI-447269; Q61221:Hif1a (xeno); NbExp=2; IntAct=EBI-447295, EBI-298954; Q9QXM1:Jmy (xeno); NbExp=16; IntAct=EBI-447295, EBI-866001; Q92831:KAT2B; NbExp=2; IntAct=EBI-447295, EBI-477430; P55209:NAP1L1; NbExp=3; IntAct=EBI-447295, EBI-356392; P20265:POU3F2; NbExp=3; IntAct=EBI-447295, EBI-1167176; Q96EB6:SIRT1; NbExp=2; IntAct=EBI-447295, EBI-1802965; Q13309:SKP2; NbExp=3; IntAct=EBI-447295, EBI-456291; P05549:TFAP2A; NbExp=7; IntAct=EBI-447295, EBI-347351; P04637:TP53; NbExp=7; IntAct=EBI-447295, EBI-366083; P67809:YBX1; NbExp=2; IntAct=EBI-447295, EBI-354065; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Co-localizes with ROCK2 in the nucleus. DOMAIN: The CRD1 domain (cell cycle regulatory domain 1) mediates transcriptional repression of a subset of p300 responsive genes; it can be de-repressed by CDKN1A/p21WAF1 at least at some promoters. It conatins sumoylation and acetylation sites and the same lysine residues may be targeted for the respective modifications. It is proposed that deacetylation by SIRT1 allows sumoylation leading to suppressed activity. PTM: Acetylated on Lys at up to 17 positions by intermolecular autocatalysis. Deacetylated in the transcriptional repression domain (CRD1) by SIRT1, preferentially at Lys-1020. 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; sumoylation in the transcriptional repression domain (CRD1) mediates transcriptional repression. 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. Phosphorylation at Ser-89 by AMPK reduces interaction with nuclear receptors, such as PPARG. 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 KAT6A. 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";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q09472
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.