Reviewed, UniProtKB/Swiss-Prot Q09472 (EP300_HUMAN)

Names and origin

Protein names

Recommended name:
    Histone acetyltransferase p300
    EC=2.3.1.48
Alternative name(s):
    E1A-associated protein p300

Gene names

Name:	EP300
Synonyms:	P300

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2414 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB 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.
Catalytic activity	Acetyl-CoA + histone = CoA + acetylhistone.
Subunit structure	Interacts with phosphorylated CREB1 By similarity. Interacts with DTX1, EID1, ELF3, FEN1, LEF1, NCOA1, NCOA6, NR3C1, PCAF, PELP1, SPIB, SRY, TCF7L2, TP53, 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 the C-terminal region of CITED4. Interacts with HTLV-1 Tax and p30II. Interacts with and acetylates HIV-1 Tat.
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated. 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. Citrullinated at Arg-2142 by PADI4, which impairs methylation by CARM1 and promotes interaction with NCOA2/GRIP1.
Involvement in disease	Defects in EP300 may play a role in epithelial cancer. Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with MYST3. Defects in EP300 are a cause of Rubinstein-Taybi syndrome (RSTS) [MIM:180849]. RSTS is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.
Sequence similarities	Contains 1 bromo domain. Contains 1 KIX domain. Contains 2 TAZ-type zinc fingers. Contains 1 ZZ-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation
Domain	Bromodomain Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Transferase
PTM	Acetylation Citrullination Methylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	N-terminal peptidyl-lysine acetylation Inferred from direct assay. Source: UniProtKB apoptosis Inferred from mutant phenotype. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW histone acetylation Inferred from electronic annotation. Source: InterPro homeostatic process Traceable author statement. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Traceable author statement. Source: ProtInc positive regulation of transcription factor activity Inferred from direct assay. Source: UniProtKB response to hypoxia Inferred from direct assay. Source: UniProtKB signal transduction Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HPA histone acetyltransferase complex Inferred from electronic annotation. Source: InterPro
Molecular function	histone acetyltransferase activity Inferred from direct assay. Source: UniProtKB protein C-terminus binding Traceable author statement. Source: ProtInc transcription coactivator activity Inferred from direct assay. Source: UniProtKB transcription factor activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CITED2	Q99967	1	EBI-447295,EBI-937732
EPAS1	Q99814	1	EBI-447295,EBI-447470
HIF1A	Q16665	2	EBI-447295,EBI-447269
His2A	P84051	1	EBI-447295,EBI-182580	From a different organism.
His3	P02299	1	EBI-447295,EBI-522090	From a different organism.
His4	P84040	1	EBI-447295,EBI-185028	From a different organism.
IFNAR1	P17181	1	EBI-447295,EBI-1547250
IFNAR2	P48551	1	EBI-447295,EBI-958408
Jmy	Q9QXM1	6	EBI-447295,EBI-866001	From a different organism.
MYC	P01106	1	EBI-447295,EBI-447544
NAP1L1	P55209	2	EBI-447295,EBI-356392
NCOA3	Q9Y6Q9	1	EBI-447295,EBI-81196
PCAF	Q92831	2	EBI-447295,EBI-477430
POU3F2	P20265	2	EBI-447295,EBI-1167176
PPARG	P37231	1	EBI-447295,EBI-781384
TFAP2A	P05549	1	EBI-447295,EBI-347351
TP53	P04637	3	EBI-447295,EBI-366083
Tp53	P02340	1	EBI-447295,EBI-474016	From a different organism.
ZBTB17	Q13105	1	EBI-447295,EBI-372156

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2414

2414

Histone acetyltransferase p300

PRO_0000211193

Regions

Domain

566 – 645

80

KIX

Domain

1067 – 1139

73

Bromo

Zinc finger

331 – 417

87

TAZ-type 1

Zinc finger

1664 – 1707

44

ZZ-type

Zinc finger

1728 – 1809

82

TAZ-type 2

Region

1572 – 1818

247

Binding region for E1A adenovirus

Region

2003 – 2212

210

Interaction with HTLV-1 Tax

Region

2041 – 2240

200

Interaction with NCOA2

Motif

11 – 17

7

Nuclear localization signal Potential

Compositional bias

797 – 800

4

Poly-Ser

Compositional bias

1519 – 1526

8

Poly-Glu

Compositional bias

2066 – 2069

4

Poly-Gln

Compositional bias

2190 – 2195

6

Poly-Gln

Sites

Site

31 – 32

2

Breakpoint for translocation to form MYST3-EP300 and EP300-MYST3

Site

2088

1

Interaction with NCOA2

Site

2142

1

Interaction with NCOA2

Amino acid modifications

Modified residue

580

1

Omega-N-methylated arginine

Modified residue

604

1

Omega-N-methylated arginine

Modified residue

1554

1

N6-acetyllysine

Modified residue

1555

1

N6-acetyllysine

Modified residue

1558

1

N6-acetyllysine

Modified residue

1560

1

N6-acetyllysine

Modified residue

2142

1

Asymmetric dimethylarginine; alternate

Modified residue

2142

1

Citrulline; alternate

Natural variations

Natural variant

827

1

L → P in breast cancer.

VAR_014428

Natural variant

997

1

I → V: dbSNP rs20551.

VAR_020425

Natural variant

1013

1

E → G in breast cancer.

VAR_014429

Natural variant

1650

1

S → Y in pancreatic cancer.

VAR_014430

Natural variant

2174

1

T → S: dbSNP rs5758252.

VAR_038376

Natural variant

2221

1

P → Q in colorectal cancer. dbSNP rs28937578.

VAR_014431

Natural variant

2223

1

P → Q: dbSNP rs1046088.

VAR_038377

Experimental info

Mutagenesis

2056

1

R → K: No effect on interaction with NCOA2

Mutagenesis

2088

1

R → K: Abolishes interaction with NCOA2

Mutagenesis

2142

1

R → K: Strongly reduces interaction with NCOA2

Secondary structure

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2414

Helix Strand Turn

Details...

Helix

332 – 334

3

Helix

335 – 355

21

Turn

356 – 358

3

Helix

367 – 379

13

Beta strand

386 – 389

4

Helix

391 – 405

15

Helix

414 – 418

5

Helix

1297 – 1313

17

Beta strand

1321 – 1334

14

Helix

1339 – 1342

4

Turn

1343 – 1347

5

Beta strand

1351 – 1366

16

Beta strand

1369 – 1381

13

Beta strand

1392 – 1400

9

Helix

1407 – 1409

3

Helix

1410 – 1428

19

Beta strand

1432 – 1436

5

Beta strand

1446 – 1450

5

Helix

1460 – 1476

17

Beta strand

1482 – 1485

4

Helix

1486 – 1493

8

Helix

1498 – 1500

3

Helix

1508 – 1517

10

Helix

1582 – 1590

9

Helix

1592 – 1594

3

Beta strand

1595 – 1601

7

Helix

1603 – 1606

4

Helix

1622 – 1624

3

Beta strand

1625 – 1627

3

Helix

1628 – 1636

9

Helix

1644 – 1662

19

Sequences

	Sequence		Length	Mass (Da)
	Q09472-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 6BFF909EE4B9D693	FASTA	2,414	264,144
	10 20 30 40 50 60 MAENVVEPGP PSAKRPKLSS PALSASASDG TDFGSLFDLE HDLPDELINS TELGLTNGGD 70 80 90 100 110 120 INQLQTSLGM VQDAASKHKQ LSELLRSGSS PNLNMGVGGP GQVMASQAQQ SSPGLGLINS 130 140 150 160 170 180 MVKSPMTQAG LTSPNMGMGT SGPNQGPTQS TGMMNSPVNQ PAMGMNTGTN AGMNPGMLAA 190 200 210 220 230 240 GNGQGIMPNQ VMNGSIGAGR GRQDMQYPNP GMGSAGNLLT EPLQQGSPQM GGQTGLRGPQ 250 260 270 280 290 300 PLKMGMMNNP NPYGSPYTQN PGQQIGASGL GLQIQTKTVL SNNLSPFAMD KKAVPGGGMP 310 320 330 340 350 360 NMGQQPAPQV QQPGLVTPVA QGMGSGAHTA DPEKRKLIQQ QLVLLLHAHK CQRREQANGE 370 380 390 400 410 420 VRQCNLPHCR TMKNVLNHMT HCQSGKSCQV AHCASSRQII SHWKNCTRHD CPVCLPLKNA 430 440 450 460 470 480 GDKRNQQPIL TGAPVGLGNP SSLGVGQQSA PNLSTVSQID PSSIERAYAA LGLPYQVNQM 490 500 510 520 530 540 PTQPQVQAKN QQNQQPGQSP QGMRPMSNMS ASPMGVNGGV GVQTPSLLSD SMLHSAINSQ 550 560 570 580 590 600 NPMMSENASV PSLGPMPTAA QPSTTGIRKQ WHEDITQDLR NHLVHKLVQA IFPTPDPAAL 610 620 630 640 650 660 KDRRMENLVA YARKVEGDMY ESANNRAEYY HLLAEKIYKI QKELEEKRRT RLQKQNMLPN 670 680 690 700 710 720 AAGMVPVSMN PGPNMGQPQP GMTSNGPLPD PSMIRGSVPN QMMPRITPQS GLNQFGQMSM 730 740 750 760 770 780 AQPPIVPRQT PPLQHHGQLA QPGALNPPMG YGPRMQQPSN QGQFLPQTQF PSQGMNVTNI 790 800 810 820 830 840 PLAPSSGQAP VSQAQMSSSS CPVNSPIMPP GSQGSHIHCP QLPQPALHQN SPSPVPSRTP 850 860 870 880 890 900 TPHHTPPSIG AQQPPATTIP APVPTPPAMP PGPQSQALHP PPRQTPTPPT TQLPQQVQPS 910 920 930 940 950 960 LPAAPSADQP QQQPRSQQST AASVPTPNAP LLPPQPATPL SQPAVSIEGQ VSNPPSTSST 970 980 990 1000 1010 1020 EVNSQAIAEK QPSQEVKMEA KMEVDQPEPA DTQPEDISES KVEDCKMEST ETEERSTELK 1030 1040 1050 1060 1070 1080 TEIKEEEDQP STSATQSSPA PGQSKKKIFK PEELRQALMP TLEALYRQDP ESLPFRQPVD 1090 1100 1110 1120 1130 1140 PQLLGIPDYF DIVKSPMDLS TIKRKLDTGQ YQEPWQYVDD IWLMFNNAWL YNRKTSRVYK 1150 1160 1170 1180 1190 1200 YCSKLSEVFE QEIDPVMQSL GYCCGRKLEF SPQTLCCYGK QLCTIPRDAT YYSYQNRYHF 1210 1220 1230 1240 1250 1260 CEKCFNEIQG ESVSLGDDPS QPQTTINKEQ FSKRKNDTLD PELFVECTEC GRKMHQICVL 1270 1280 1290 1300 1310 1320 HHEIIWPAGF VCDGCLKKSA RTRKENKFSA KRLPSTRLGT FLENRVNDFL RRQNHPESGE 1330 1340 1350 1360 1370 1380 VTVRVVHASD KTVEVKPGMK ARFVDSGEMA ESFPYRTKAL FAFEEIDGVD LCFFGMHVQE 1390 1400 1410 1420 1430 1440 YGSDCPPPNQ RRVYISYLDS VHFFRPKCLR TAVYHEILIG YLEYVKKLGY TTGHIWACPP 1450 1460 1470 1480 1490 1500 SEGDDYIFHC HPPDQKIPKP KRLQEWYKKM LDKAVSERIV HDYKDIFKQA TEDRLTSAKE 1510 1520 1530 1540 1550 1560 LPYFEGDFWP NVLEESIKEL EQEEEERKRE ENTSNESTDV TKGDSKNAKK KNNKKTSKNK 1570 1580 1590 1600 1610 1620 SSLSRGNKKK PGMPNVSNDL SQKLYATMEK HKEVFFVIRL IAGPAANSLP PIVDPDPLIP 1630 1640 1650 1660 1670 1680 CDLMDGRDAF LTLARDKHLE FSSLRRAQWS TMCMLVELHT QSQDRFVYTC NECKHHVETR 1690 1700 1710 1720 1730 1740 WHCTVCEDYD LCITCYNTKN HDHKMEKLGL GLDDESNNQQ AAATQSPGDS RRLSIQRCIQ 1750 1760 1770 1780 1790 1800 SLVHACQCRN ANCSLPSCQK MKRVVQHTKG CKRKTNGGCP ICKQLIALCC YHAKHCQENK 1810 1820 1830 1840 1850 1860 CPVPFCLNIK QKLRQQQLQH RLQQAQMLRR RMASMQRTGV VGQQQGLPSP TPATPTTPTG 1870 1880 1890 1900 1910 1920 QQPTTPQTPQ PTSQPQPTPP NSMPPYLPRT QAAGPVSQGK AAGQVTPPTP PQTAQPPLPG 1930 1940 1950 1960 1970 1980 PPPTAVEMAM QIQRAAETQR QMAHVQIFQR PIQHQMPPMT PMAPMGMNPP PMTRGPSGHL 1990 2000 2010 2020 2030 2040 EPGMGPTGMQ QQPPWSQGGL PQPQQLQSGM PRPAMMSVAQ HGQPLNMAPQ PGLGQVGISP 2050 2060 2070 2080 2090 2100 LKPGTVSQQA LQNLLRTLRS PSSPLQQQQV LSILHANPQL LAAFIKQRAA KYANSNPQPI 2110 2120 2130 2140 2150 2160 PGQPGMPQGQ PGLQPPTMPG QQGVHSNPAM QNMNPMQAGV QRAGLPQQQP QQQLQPPMGG 2170 2180 2190 2200 2210 2220 MSPQAQQMNM NHNTMPSQFR DILRRQQMMQ QQQQQGAGPG IGPGMANHNQ FQQPQGVGYP 2230 2240 2250 2260 2270 2280 PQPQQRMQHH MQQMQQGNMG QIGQLPQALG AEAGASLQAY QQRLLQQQMG SPVQPNPMSP 2290 2300 2310 2320 2330 2340 QQHMLPNQAQ SPHLQGQQIP NSLSNQVRSP QPVPSPRPQS QPPHSSPSPR MQPQPSPHHV 2350 2360 2370 2380 2390 2400 SPQTSSPHPG LVAAQANPME QGHFASPDQN SMLSQLASNP GMANLHGASA TDLGLSTDNS 2410 DLNSNLSQST LDIH

References

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[1]	"Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p30