B2RWS6 (EP300_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 58. History...
Names and origin
|Protein names||Recommended name:|
Histone acetyltransferase p300
Short name=p300 HAT
E1A-associated protein p300
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||2415 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac). 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. Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity By similarity. Ref.2
Acetyl-CoA + [histone] = CoA + acetyl-[histone].
Interacts with phosphorylated CREB1. 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 HIPK2, 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. 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 with PPARG By similarity. Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes By similarity. Interacts with CITED1 and CITED2. Interacts with ROCK2 By similarity. Interacts with NEUROD1. Interacts (via CREB-binding domain) with MYOCD (via C-terminus). 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 ALKBH4 and DDIT3/CHOP By similarity. Interacts with KLF15 By similarity. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6
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 By similarity.
Acetylated on Lys at up to 17 positions by intermolecular autocatalysis. Deacetylated in the transcriptional repression domain (CRD1) by SIRT1, preferentially at Lys-1019 By similarity.
Citrullinated at Arg-2143 by PADI4, which impairs methylation by CARM1 and promotes interaction with NCOA2/GRIP1 By similarity.
Methylated at Arg-581 and Arg-605 in the KIX domain by CARM1, which blocks association with CREB, inhibits CREB signaling and activates apoptotic response. Also methylated at Arg-2143 by CARM1, which impairs interaction with NCOA2/GRIP1 By similarity.
Sumoylated; sumoylation in the transcriptional repression domain (CRD1) mediates transcriptional repression. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3 By similarity.
Probable target of ubiquitination by FBXO3, leading to rapid proteasome-dependent degradation By similarity.
Phosphorylation at Ser-89 by AMPK reduces interaction with nuclear receptors, such as PPARG By similarity. 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 By similarity. Ref.6
Contains 1 bromo domain.
Contains 1 KIX domain.
Contains 2 TAZ-type zinc fingers.
Contains 1 ZZ-type zinc finger.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 2415||2414||Histone acetyltransferase p300||PRO_0000409386|
|Domain||567 – 646||80||KIX|
|Domain||1066 – 1138||73||Bromo|
|Zinc finger||332 – 418||87||TAZ-type 1|
|Zinc finger||1663 – 1706||44||ZZ-type|
|Zinc finger||1727 – 1808||82||TAZ-type 2|
|Region||2 – 139||138||Interaction with ALX1 By similarity|
|Region||1016 – 1028||13||CRD1; mediates transcriptional repression By similarity|
|Region||2042 – 2240||199||Interaction with NCOA2 By similarity|
|Coiled coil||1510 – 1539||30||Potential|
|Motif||11 – 17||7||Nuclear localization signal Potential|
|Compositional bias||660 – 942||283||Pro-rich|
|Compositional bias||798 – 801||4||Poly-Ser|
|Compositional bias||1518 – 1525||8||Poly-Glu|
|Metal binding||348||1||Zinc 1 By similarity|
|Metal binding||352||1||Zinc 1 By similarity|
|Metal binding||365||1||Zinc 1 By similarity|
|Metal binding||370||1||Zinc 1 By similarity|
|Metal binding||379||1||Zinc 2 By similarity|
|Metal binding||383||1||Zinc 2 By similarity|
|Metal binding||389||1||Zinc 2 By similarity|
|Metal binding||394||1||Zinc 2 By similarity|
|Metal binding||403||1||Zinc 3 By similarity|
|Metal binding||407||1||Zinc 3 By similarity|
|Metal binding||412||1||Zinc 3 By similarity|
|Metal binding||415||1||Zinc 3 By similarity|
|Site||2089||1||Interaction with NCOA2 By similarity|
|Site||2143||1||Interaction with NCOA2 By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||89||1||Phosphoserine; by AMPK By similarity|
|Modified residue||286||1||Phosphoserine By similarity|
|Modified residue||581||1||Omega-N-methylated arginine; by CARM1 By similarity|
|Modified residue||605||1||Omega-N-methylated arginine; by CARM1 By similarity|
|Modified residue||637||1||N6-acetyllysine By similarity|
|Modified residue||885||1||Phosphothreonine By similarity|
|Modified residue||887||1||Phosphothreonine By similarity|
|Modified residue||976||1||N6-acetyllysine By similarity|
|Modified residue||980||1||N6-acetyllysine By similarity|
|Modified residue||1019||1||N6-acetyllysine; alternate By similarity|
|Modified residue||1023||1||N6-acetyllysine; alternate By similarity|
|Modified residue||1037||1||Phosphoserine By similarity|
|Modified residue||1102||1||N6-acetyllysine By similarity|
|Modified residue||1335||1||N6-acetyllysine By similarity|
|Modified residue||1472||1||N6-acetyllysine By similarity|
|Modified residue||1498||1||N6-acetyllysine; by autocatalysis By similarity|
|Modified residue||1541||1||N6-acetyllysine By similarity|
|Modified residue||1545||1||N6-acetyllysine By similarity|
|Modified residue||1548||1||N6-acetyllysine; by autocatalysis By similarity|
|Modified residue||1553||1||N6-acetyllysine; by autocatalysis By similarity|
|Modified residue||1554||1||N6-acetyllysine By similarity|
|Modified residue||1557||1||N6-acetyllysine By similarity|
|Modified residue||1559||1||N6-acetyllysine; by autocatalysis By similarity|
|Modified residue||1582||1||N6-acetyllysine By similarity|
|Modified residue||1589||1||N6-acetyllysine By similarity|
|Modified residue||1673||1||N6-acetyllysine By similarity|
|Modified residue||1733||1||Phosphoserine By similarity|
|Modified residue||1856||1||Phosphothreonine By similarity|
|Modified residue||1858||1||Phosphothreonine By similarity|
|Modified residue||2143||1||Asymmetric dimethylarginine; by CARM1; alternate By similarity|
|Modified residue||2143||1||Citrulline; by PADI4; alternate By similarity|
|Cross-link||1019||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity|
|Cross-link||1023||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity|
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"The basic helix-loop-helix protein BETA2 interacts with p300 to coordinate differentiation of secretin-expressing enteroendocrine cells."|
Mutoh H., Naya F.J., Tsai M.J., Leiter A.B.
Genes Dev. 12:820-830(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NEUROD1.
|||"MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression."|
Glenn D.J., Maurer R.A.
J. Biol. Chem. 274:36159-36167(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CITED2.
|||"The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors."|
Yahata T., de Caestecker M.P., Lechleider R.J., Andriole S., Roberts A.B., Isselbacher K.J., Shioda T.
J. Biol. Chem. 275:8825-8834(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CITED1.
|||"Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin."|
Cao D., Wang Z., Zhang C.L., Oh J., Xing W., Li S., Richardson J.A., Wang D.Z., Olson E.N.
Mol. Cell. Biol. 25:364-376(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOCD.
|||"Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation."|
Aikawa Y., Nguyen L.A., Isono K., Takakura N., Tagata Y., Schmitz M.L., Koseki H., Kitabayashi I.
EMBO J. 25:3955-3965(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIPK2, PHOSPHORYLATION BY HIPK2.
|+||Additional computationally mapped references.|
|BC144976 mRNA. Translation: AAI44977.1.|
BC150681 mRNA. Translation: AAI50682.1.
3D structure databases
|SMR||B2RWS6. Positions 324-424, 567-647, 1046-1160, 1286-1712, 1725-1833, 2051-2093. |
Protein-protein interaction databases
|IntAct||B2RWS6. 3 interactions.|
Protocols and materials databases
|MGI||MGI:1276116. Ep300. |
Enzyme and pathway databases
|Reactome||REACT_109335. Circadian Clock. |
REACT_115202. Signal Transduction.
REACT_127416. Developmental Biology.
REACT_24972. Circadian Clock.
REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
Gene expression databases
Family and domain databases
|Gene3D||1.10.1630.10. 1 hit. |
188.8.131.52. 1 hit.
1.20.1020.10. 2 hits.
1.20.920.10. 1 hit.
|InterPro||IPR001487. Bromodomain. |
|Pfam||PF00439. Bromodomain. 1 hit. |
PF09030. Creb_binding. 1 hit.
PF06001. DUF902. 1 hit.
PF08214. KAT11. 1 hit.
PF02172. KIX. 1 hit.
PF02135. zf-TAZ. 2 hits.
PF00569. ZZ. 1 hit.
|PRINTS||PR00503. BROMODOMAIN. |
|SMART||SM00297. BROMO. 1 hit. |
SM00551. ZnF_TAZ. 2 hits.
SM00291. ZnF_ZZ. 1 hit.
|SUPFAM||SSF47040. SSF47040. 1 hit. |
SSF47370. SSF47370. 1 hit.
SSF57933. SSF57933. 2 hits.
SSF69125. SSF69125. 1 hit.
|PROSITE||PS00633. BROMODOMAIN_1. 1 hit. |
PS50014. BROMODOMAIN_2. 1 hit.
PS50952. KIX. 1 hit.
PS50134. ZF_TAZ. 2 hits.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.
|ChiTaRS||EP300. mouse. |
|Accession||Primary (citable) accession number: B2RWS6|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|