UniProt Accession

 EP300_HUMAN; Q09472; B1AKC2 

Genbank Protein ID

 U01877; AL080243; AL035658; AL096765; AL096765; AL035658; AL080243; AL035658; AL080243; AL096765; CH471095 

Genbank Nucleotide ID

 AAA18639.1; CAH70384.1; CAH70384.1; CAH70384.1; CAH73688.1; CAH73688.1; CAH73688.1; CAI23037.1; CAI23037.1; CAI23037.1; EAW60408.1 

Protein Name

 Histone acetyltransferase p300 

Protein Synonyms/Alias

 p300 HAT; E1A-associated protein p300 

Gene Name

 EP300 

Gene Synonyms/Alias

 P300 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
14	EPGPPSAKRPKLSSP	acetylation	[1]
79	QDAASKHKQLSELLR	propionylation	[2]
291	LSPFAMDKKAVPGGG	acetylation	[1, 3]
291	LSPFAMDKKAVPGGG	butyrylation	[2]
291	LSPFAMDKKAVPGGG	propionylation	[2]
373	LPHCRTMKNVLNHMT	propionylation	[2]
601	TPDPAALKDRRMENL	propionylation	[2]
614	NLVAYARKVEGDMYE	propionylation	[2]
614	NLVAYARKVEGDMYE	ubiquitination	[4]
636	YYHLLAEKIYKIQKE	acetylation	[1, 3, 4, 5]
977	KQPSQEVKMEAKMEV	acetylation	[3, 4, 5]
981	QEVKMEAKMEVDQPE	acetylation	[1, 3]
1001	PEDISESKVEDCKME	acetylation	[1, 4]
1020	EERSTELKTEIKEEE	sumoylation	[6, 7, 8]
1024	TELKTEIKEEEDQPS	sumoylation	[6, 7, 8]
1045	SPAPGQSKKKIFKPE	propionylation	[2]
1046	PAPGQSKKKIFKPEE	propionylation	[2]
1103	PMDLSTIKRKLDTGQ	acetylation	[3]
1167	LGYCCGRKLEFSPQT	acetylation	[5]
1180	QTLCCYGKQLCTIPR	acetylation	[1, 3, 4, 5]
1336	SDKTVEVKPGMKARF	acetylation	[1, 4, 9]
1340	VEVKPGMKARFVDSG	acetylation	[1, 4]
1473	WYKKMLDKAVSERIV	acetylation	[9]
1499	EDRLTSAKELPYFEG	acetylation	[1, 3, 5, 9]
1499	EDRLTSAKELPYFEG	ubiquitination	[10]
1528	EQEEEERKREENTSN	acetylation	[3]
1542	NESTDVTKGDSKNAK	acetylation	[1, 3, 4, 5, 9, 11, 12]
1542	NESTDVTKGDSKNAK	propionylation	[2]
1546	DVTKGDSKNAKKKNN	acetylation	[3, 4, 9, 11, 12]
1546	DVTKGDSKNAKKKNN	butyrylation	[2]
1546	DVTKGDSKNAKKKNN	propionylation	[2]
1549	KGDSKNAKKKNNKKT	acetylation	[3, 9, 11, 12]
1549	KGDSKNAKKKNNKKT	butyrylation	[2]
1549	KGDSKNAKKKNNKKT	propionylation	[2]
1550	GDSKNAKKKNNKKTS	acetylation	[3, 9, 11]
1550	GDSKNAKKKNNKKTS	butyrylation	[2]
1550	GDSKNAKKKNNKKTS	propionylation	[2]
1551	DSKNAKKKNNKKTSK	acetylation	[9, 11]
1551	DSKNAKKKNNKKTSK	butyrylation	[2]
1551	DSKNAKKKNNKKTSK	propionylation	[2]
1554	NAKKKNNKKTSKNKS	acetylation	[3, 5, 9, 11, 13, 14]
1554	NAKKKNNKKTSKNKS	butyrylation	[2, 15]
1554	NAKKKNNKKTSKNKS	propionylation	[2, 15]
1555	AKKKNNKKTSKNKSS	acetylation	[3, 5, 9, 11, 13, 14, 16]
1555	AKKKNNKKTSKNKSS	butyrylation	[2, 15]
1555	AKKKNNKKTSKNKSS	propionylation	[2, 15]
1558	KNNKKTSKNKSSLSR	acetylation	[1, 3, 4, 5, 9, 11, 12, 13, 14, 16]
1558	KNNKKTSKNKSSLSR	butyrylation	[2, 15]
1558	KNNKKTSKNKSSLSR	propionylation	[2, 15]
1560	NKKTSKNKSSLSRGN	acetylation	[1, 3, 4, 5, 9, 11, 13, 14, 16]
1560	NKKTSKNKSSLSRGN	butyrylation	[2, 15]
1560	NKKTSKNKSSLSRGN	propionylation	[2, 15]
1568	SSLSRGNKKKPGMPN	butyrylation	[2]
1568	SSLSRGNKKKPGMPN	propionylation	[2]
1569	SLSRGNKKKPGMPNV	propionylation	[2]
1570	LSRGNKKKPGMPNVS	acetylation	[1, 3]
1583	VSNDLSQKLYATMEK	acetylation	[1, 3, 4, 5]
1590	KLYATMEKHKEVFFV	acetylation	[1, 3, 4, 5]
1637	FLTLARDKHLEFSSL	acetylation	[9]
1637	FLTLARDKHLEFSSL	ubiquitination	[17]
1674	VYTCNECKHHVETRW	acetylation	[3, 4, 5, 16]
1707	NHDHKMEKLGLGLDD	acetylation	[1]
1707	NHDHKMEKLGLGLDD	propionylation	[2]
1760	CSLPSCQKMKRVVQH	acetylation	[1, 4]
1762	LPSCQKMKRVVQHTK	acetylation	[1, 4]
1769	KRVVQHTKGCKRKTN	butyrylation	[2]
1769	KRVVQHTKGCKRKTN	propionylation	[2]
1772	VQHTKGCKRKTNGGC	propionylation	[2]
1794	ALCCYHAKHCQENKC	acetylation	[4]
1800	AKHCQENKCPVPFCL	acetylation	[1, 4]
1900	AGPVSQGKAAGQVTP	acetylation	[18]

Reference

 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] Lysine propionylation and butyrylation are novel post-translational modifications in histones.
 Chen Y, Sprung R, Tang Y, Ball H, Sangras B, Kim SC, Falck JR, Peng J, Gu W, Zhao Y.
 Mol Cell Proteomics. 2007 May;6(5):812-9. [PMID: 17267393]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [6] P300 transcriptional repression is mediated by SUMO modification.
 Girdwood D, Bumpass D, Vaughan OA, Thain A, Anderson LA, Snowden AW, Garcia-Wilson E, Perkins ND, Hay RT.
 Mol Cell. 2003 Apr;11(4):1043-54. [PMID: 12718889]
 [7] Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity.
 Yang SH, Jaffray E, Hay RT, Sharrocks AD.
 Mol Cell. 2003 Jul;12(1):63-74. [PMID: 12887893]
 [8] SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1.
 Bouras T, Fu M, Sauve AA, Wang F, Quong AA, Perkins ND, Hay RT, Gu W, Pestell RG.
 J Biol Chem. 2005 Mar 18;280(11):10264-76. [PMID: 15632193]
 [9] Structural analysis of a highly acetylated protein using a curved-field reflectron mass spectrometer.
 Wang D, Thompson P, Cole PA, Cotter RJ.
 Proteomics. 2005 Jun;5(9):2288-96. [PMID: 15887180]
 [10] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [11] Kinetic and mass spectrometric analysis of p300 histone acetyltransferase domain autoacetylation.
 Karanam B, Jiang L, Wang L, Kelleher NL, Cole PA.
 J Biol Chem. 2006 Dec 29;281(52):40292-301. [PMID: 17065153]
 [12] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [13] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [14] Proteome-wide prediction of acetylation substrates.
 Basu A, Rose KL, Zhang J, Beavis RC, Ueberheide B, Garcia BA, Chait B, Zhao Y, Hunt DF, Segal E, Allis CD, Hake SB.
 Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13785-90. [PMID: 19666589]
 [15] Molecular characterization of propionyllysines in non-histone proteins.
 Cheng Z, Tang Y, Chen Y, Kim S, Liu H, Li SS, Gu W, Zhao Y.
 Mol Cell Proteomics. 2009 Jan;8(1):45-52. [PMID: 18753126]
 [16] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [17] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [18] Identification of lysine acetyltransferase p300 substrates using 4-pentynoyl-coenzyme A and bioorthogonal proteomics.
 Yang YY, Grammel M, Hang HC.
 Bioorg Med Chem Lett. 2011 Sep 1;21(17):4976-9. [PMID: 21669532] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 566 645 KIX.
 DOMAIN 1067 1139 Bromo.
 ZN_FING 331 417 TAZ-type 1.
 ZN_FING 1664 1707 ZZ-type.
 ZN_FING 1728 1809 TAZ-type 2.
 REGION 2 139 Interaction with ALX1.
 REGION 1017 1029 CRD1; mediates transcriptional
 REGION 1572 1818 Binding region for E1A adenovirus.
 REGION 2003 2212 Interaction with HTLV-1 Tax.
 REGION 2041 2240 Interaction with NCOA2.
 MOTIF 11 17 Nuclear localization signal (Potential).
 METAL 347 347 Zinc 1.
 METAL 351 351 Zinc 1.
 METAL 364 364 Zinc 1.
 METAL 369 369 Zinc 1.
 METAL 378 378 Zinc 2.
 METAL 382 382 Zinc 2.
 METAL 388 388 Zinc 2.
 METAL 393 393 Zinc 2.
 METAL 402 402 Zinc 3.
 METAL 406 406 Zinc 3.
 METAL 411 411 Zinc 3.
 METAL 414 414 Zinc 3.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 89 89 Phosphoserine; by AMPK.
 MOD_RES 285 285 Phosphoserine.
 MOD_RES 580 580 Omega-N-methylated arginine; by CARM1.
 MOD_RES 604 604 Omega-N-methylated arginine; by CARM1.
 MOD_RES 636 636 N6-acetyllysine.
 MOD_RES 885 885 Phosphothreonine.
 MOD_RES 887 887 Phosphothreonine.
 MOD_RES 977 977 N6-acetyllysine.
 MOD_RES 981 981 N6-acetyllysine.
 MOD_RES 1020 1020 N6-acetyllysine; alternate.
 MOD_RES 1024 1024 N6-acetyllysine; alternate.
 MOD_RES 1038 1038 Phosphoserine.
 MOD_RES 1103 1103 N6-acetyllysine.
 MOD_RES 1336 1336 N6-acetyllysine.
 MOD_RES 1473 1473 N6-acetyllysine.
 MOD_RES 1499 1499 N6-acetyllysine; by autocatalysis.
 MOD_RES 1542 1542 N6-acetyllysine.
 MOD_RES 1546 1546 N6-acetyllysine.
 MOD_RES 1549 1549 N6-acetyllysine; by autocatalysis.
 MOD_RES 1554 1554 N6-acetyllysine; by autocatalysis.
 MOD_RES 1555 1555 N6-acetyllysine.
 MOD_RES 1558 1558 N6-acetyllysine.
 MOD_RES 1560 1560 N6-acetyllysine; by autocatalysis.
 MOD_RES 1583 1583 N6-acetyllysine.
 MOD_RES 1590 1590 N6-acetyllysine.
 MOD_RES 1674 1674 N6-acetyllysine.
 MOD_RES 1734 1734 Phosphoserine.
 MOD_RES 1857 1857 Phosphothreonine.
 MOD_RES 1859 1859 Phosphothreonine.
 MOD_RES 2142 2142 Asymmetric dimethylarginine; by CARM1;
 MOD_RES 2142 2142 Citrulline; by PADI4; alternate.
 CROSSLNK 1020 1020 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 1024 1024 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Bromodomain; Cell cycle; Chromosomal rearrangement; Citrullination; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Host-virus interaction; Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 2414 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:HPA.
 GO:0000123; C:histone acetyltransferase complex; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005667; C:transcription factor complex; IEA:Compara.
 GO:0003682; F:chromatin binding; IMP:UniProtKB.
 GO:0031490; F:chromatin DNA binding; IEA:Compara.
 GO:0001047; F:core promoter binding; IDA:UniProtKB.
 GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB.
 GO:0004468; F:lysine N-acetyltransferase activity; IDA:UniProtKB.
 GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0007507; P:heart development; IEA:Compara.
 GO:0043967; P:histone H4 acetylation; IMP:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:UniProtKB.
 GO:0030324; P:lung development; IEA:Compara.
 GO:0018076; P:N-terminal peptidyl-lysine acetylation; IDA:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0007399; P:nervous system development; TAS:ProtInc.
 GO:0007219; P:Notch signaling pathway; TAS:Reactome.
 GO:0009887; P:organ morphogenesis; IEA:Compara.
 GO:0043923; P:positive regulation by host of viral transcription; IDA:BHF-UCL.
 GO:0032092; P:positive regulation of protein binding; IEA:Compara.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0060765; P:regulation of androgen receptor signaling pathway; IDA:BHF-UCL.
 GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
 GO:0043627; P:response to estrogen stimulus; IDA:UniProtKB.
 GO:0007519; P:skeletal muscle tissue development; IEA:Compara.
 GO:0001756; P:somitogenesis; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR001487; Bromodomain.
 IPR018359; Bromodomain_CS.
 IPR010303; DUF902_CREBbp.
 IPR013178; Histone_H3-K56_AcTrfase_RTT109.
 IPR003101; KIX_dom.
 IPR009110; Nuc_rcpt_coact.
 IPR014744; Nuc_rcpt_coact_CREBbp.
 IPR000197; Znf_TAZ.
 IPR000433; Znf_ZZ. 

Pfam

 PF00439; Bromodomain
 PF09030; Creb_binding
 PF06001; DUF902
 PF08214; KAT11
 PF02172; KIX
 PF02135; zf-TAZ
 PF00569; ZZ 

SMART

 SM00297; BROMO
 SM00551; ZnF_TAZ
 SM00291; ZnF_ZZ 

PROSITE

 PS00633; BROMODOMAIN_1
 PS50014; BROMODOMAIN_2
 PS50952; KIX
 PS50134; ZF_TAZ
 PS01357; ZF_ZZ_1
 PS50135; ZF_ZZ_2 

PRINTS

 PR00503; BROMODOMAIN.