Reviewed, UniProtKB/Swiss-Prot Q92793 (CBP_HUMAN)

Names and origin

Protein names

Recommended name:
    CREB-binding protein
    EC=2.3.1.48

Gene names

Name:	CREBBP
Synonyms:	CBP

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	2442 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 coactivator. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes.
Catalytic activity	Acetyl-CoA + histone = CoA + acetylhistone.
Subunit structure	Found in a complex containing NCOA2; NCOA3; IKKA; IKKB and IKBKG. Probably part of a complex with HIF1A and EP300. Interacts with phosphorylated CREB1. Interacts with the C-terminal region of CITED4. The TAZ-type 1 domain interacts with HIF1A. Interacts with SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB and TRERF1. Interacts with HTLV-1 Tax and p30II. Interacts with HIV-1 Tat. Interacts with KLF1; the interaction results in acetylation of KLF1 and enhancement of its transcriptional activity. Interacts with ZCCHC12 By similarity.
Subcellular location	Nucleus.
Domain	The KIX domain mediates binding to HIV-1 Tat.
Post-translational modification	Methylation of the KIX domain by CARM1 blocks association with CREB. This results in the blockade of CREB signaling, and in activation of apoptotic response By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with MYST3/MOZ; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with MYST4/MORF. MYST3-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP 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	Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement
Disease	Disease mutation
Domain	Bromodomain Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Activator Transferase
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	N-terminal peptidyl-lysine acetylation Inferred from direct assay. Source: UniProtKB histone acetylation Ref.28 Inferred from direct assay. Source: UniProtKB homeostatic process Non-traceable author statement. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription Ref.28 Inferred from direct assay. Source: UniProtKB protein complex assembly Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from direct assay. Source: HGNC response to hypoxia Traceable author statement. Source: UniProtKB signal transduction Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Traceable author statement. Source: ProtInc histone acetyltransferase complex Inferred from electronic annotation. Source: InterPro
Molecular function	MyoD binding Inferred from direct assay. Source: UniProtKB histone acetyltransferase activity Ref.28 Inferred from direct assay. Source: UniProtKB signal transducer activity Traceable author statement. Source: ProtInc transcription coactivator activity Ref.6 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
DAXX	Q9UER7	1	EBI-81215,EBI-77321
HTT	P42858	1	EBI-81215,EBI-466029
IFNAR2	P48551	3	EBI-81215,EBI-958408
MTDH	Q86UE4	1	EBI-81215,EBI-1046588
NAP1L1	P55209	2	EBI-81215,EBI-356392
NCOA6	Q14686	1	EBI-81215,EBI-78670
PCAF	Q92831	2	EBI-81215,EBI-477430
RELA	Q04206	1	EBI-81215,EBI-73886
RPA2	P15927	1	EBI-81215,EBI-621404
TP53	P04637	3	EBI-81215,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2442

2442

CREB-binding protein

PRO_0000211190

Regions

Domain

587 – 666

80

KIX

Domain

1103 – 1175

73

Bromo

Zinc finger

347 – 433

87

TAZ-type 1

Zinc finger

1701 – 1744

44

ZZ-type

Zinc finger

1765 – 1846

82

TAZ-type 2

Region

227 – 410

184

Interaction with SRCAP

Region

1460 – 1891

432

Interaction with TRERF1

Compositional bias

1061 – 1064

4

Poly-Glu

Compositional bias

1199 – 1487

289

Cys/His-rich

Compositional bias

1555 – 1562

8

Poly-Glu

Compositional bias

1943 – 1948

6

Poly-Pro

Compositional bias

1967 – 1970

4

Poly-Gln

Compositional bias

2081 – 2085

5

Poly-Gln

Compositional bias

2199 – 2216

18

Poly-Gln

Compositional bias

2245 – 2248

4

Poly-Gln

Compositional bias

2297 – 2300

4

Poly-Gln

Sites

Site

29 – 30

2

Breakpoint for translocation to form MYST4-CREBBP

Site

266 – 267

2

Breakpoint for translocation to form MYST3-CREBBP

Amino acid modifications

Modified residue

121

1

Phosphoserine

Modified residue

124

1

Phosphoserine

Modified residue

601

1

Omega-N-methylated arginine By similarity

Modified residue

625

1

Omega-N-methylated arginine By similarity

Modified residue

1001

1

Phosphothreonine

Modified residue

1030

1

Phosphoserine

Modified residue

1072

1

Phosphoserine

Modified residue

1588

1

N6-acetyllysine

Modified residue

1591

1

N6-acetyllysine

Modified residue

1592

1

N6-acetyllysine

Modified residue

1595

1

N6-acetyllysine

Modified residue

1597

1

N6-acetyllysine

Modified residue

1755

1

Phosphoserine

Modified residue

2063

1

Phosphoserine

Modified residue

2076

1

Phosphoserine

Modified residue

2079

1

Phosphoserine

Natural variations

Natural variant

1175

1

Y → C in RSTS; mild form. dbSNP rs28937315.

VAR_037305

Natural variant

1278

1

E → K in RSTS; abolishes acetyltransferase activity.

VAR_035080

Natural variant

1378

1

R → P in RSTS; abolishes acetyltransferase activity and the ability of transactivate CREB.

VAR_015578

Natural variant

1414

1

V → I: dbSNP rs130015.

VAR_027953

Natural variant

1447

1

T → I in RSTS.

VAR_035081

Natural variant

1450

1

Y → H in RSTS.

VAR_035082

Natural variant

1470

1

H → R in RSTS.

VAR_035083

Natural variant

1664

1

R → H in RSTS; abolishes acetyltransferase activity.

VAR_035084

Experimental info

Sequence conflict

1511 – 1513

3

FAE → NSG in AAC51340. Ref.2

Sequence conflict

1724 – 1725

2

ED → VV in AAC51340. Ref.2

Sequence conflict

1770

1

L → V in AAC51770. Ref.1

Sequence conflict

1789

1

N → F in AAC51340. Ref.2

Sequence conflict

1812

1

T → P in AAC51340. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

2442

Helix Strand Turn

Details...

Helix

377 – 379

3

Turn

383 – 388

6

Helix

391 – 395

5

Helix

1087 – 1102

16

Beta strand

1105 – 1109

5

Helix

1117 – 1120

4

Turn

1123 – 1127

5

Helix

1135 – 1144

10

Helix

1150 – 1167

18

Turn

1168 – 1170

3

Helix

1173 – 1196

24

Sequences

	Sequence		Length	Mass (Da)
	Q92793-1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 3BEA9B8558BA1A5E	FASTA	2,442	265,351
	10 20 30 40 50 60 MAENLLDGPP NPKRAKLSSP GFSANDSTDF GSLFDLENDL PDELIPNGGE LGLLNSGNLV 70 80 90 100 110 120 PDAASKHKQL SELLRGGSGS SINPGIGNVS ASSPVQQGLG GQAQGQPNSA NMASLSAMGK 130 140 150 160 170 180 SPLSQGDSSA PSLPKQAAST SGPTPAASQA LNPQAQKQVG LATSSPATSQ TGPGICMNAN 190 200 210 220 230 240 FNQTHPGLLN SNSGHSLINQ ASQGQAQVMN GSLGAAGRGR GAGMPYPTPA MQGASSSVLA 250 260 270 280 290 300 ETLTQVSPQM TGHAGLNTAQ AGGMAKMGIT GNTSPFGQPF SQAGGQPMGA TGVNPQLASK 310 320 330 340 350 360 QSMVNSLPTF PTDIKNTSVT NVPNMSQMQT SVGIVPTQAI ATGPTADPEK RKLIQQQLVL 370 380 390 400 410 420 LLHAHKCQRR EQANGEVRAC SLPHCRTMKN VLNHMTHCQA GKACQVAHCA SSRQIISHWK 430 440 450 460 470 480 NCTRHDCPVC LPLKNASDKR NQQTILGSPA SGIQNTIGSV GTGQQNATSL SNPNPIDPSS 490 500 510 520 530 540 MQRAYAALGL PYMNQPQTQL QPQVPGQQPA QPQTHQQMRT LNPLGNNPMN IPAGGITTDQ 550 560 570 580 590 600 QPPNLISESA LPTSLGATNP LMNDGSNSGN IGTLSTIPTA APPSSTGVRK GWHEHVTQDL 610 620 630 640 650 660 RSHLVHKLVQ AIFPTPDPAA LKDRRMENLV AYAKKVEGDM YESANSRDEY YHLLAEKIYK 670 680 690 700 710 720 IQKELEEKRR SRLHKQGILG NQPALPAPGA QPPVIPQAQP VRPPNGPLSL PVNRMQVSQG 730 740 750 760 770 780 MNSFNPMSLG NVQLPQAPMG PRAASPMNHS VQMNSMGSVP GMAISPSRMP QPPNMMGAHT 790 800 810 820 830 840 NNMMAQAPAQ SQFLPQNQFP SSSGAMSVGM GQPPAQTGVS QGQVPGAALP NPLNMLGPQA 850 860 870 880 890 900 SQLPCPPVTQ SPLHPTPPPA STAAGMPSLQ HTTPPGMTPP QPAAPTQPST PVSSSGQTPT 910 920 930 940 950 960 PTPGSVPSAT QTQSTPTVQA AAQAQVTPQP QTPVQPPSVA TPQSSQQQPT PVHAQPPGTP 970 980 990 1000 1010 1020 LSQAAASIDN RVPTPSSVAS AETNSQQPGP DVPVLEMKTE TQAEDTEPDP GESKGEPRSE 1030 1040 1050 1060 1070 1080 MMEEDLQGAS QVKEETDIAE QKSEPMEVDE KKPEVKVEVK EEEESSSNGT ASQSTSPSQP 1090 1100 1110 1120 1130 1140 RKKIFKPEEL RQALMPTLEA LYRQDPESLP FRQPVDPQLL GIPDYFDIVK NPMDLSTIKR 1150 1160 1170 1180 1190 1200 KLDTGQYQEP WQYVDDVWLM FNNAWLYNRK TSRVYKFCSK LAEVFEQEID PVMQSLGYCC 1210 1220 1230 1240 1250 1260 GRKYEFSPQT LCCYGKQLCT IPRDAAYYSY QNRYHFCEKC FTEIQGENVT LGDDPSQPQT 1270 1280 1290 1300 1310 1320 TISKDQFEKK KNDTLDPEPF VDCKECGRKM HQICVLHYDI IWPSGFVCDN CLKKTGRPRK 1330 1340 1350 1360 1370 1380 ENKFSAKRLQ TTRLGNHLED RVNKFLRRQN HPEAGEVFVR VVASSDKTVE VKPGMKSRFV 1390 1400 1410 1420 1430 1440 DSGEMSESFP YRTKALFAFE EIDGVDVCFF GMHVQEYGSD CPPPNTRRVY ISYLDSIHFF 1450 1460 1470 1480 1490 1500 RPRCLRTAVY HEILIGYLEY VKKLGYVTGH IWACPPSEGD DYIFHCHPPD QKIPKPKRLQ 1510 1520 1530 1540 1550 1560 EWYKKMLDKA FAERIIHDYK DIFKQATEDR LTSAKELPYF EGDFWPNVLE ESIKELEQEE 1570 1580 1590 1600 1610 1620 EERKKEESTA ASETTEGSQG DSKNAKKKNN KKTNKNKSSI SRANKKKPSM PNVSNDLSQK 1630 1640 1650 1660 1670 1680 LYATMEKHKE VFFVIHLHAG PVINTLPPIV DPDPLLSCDL MDGRDAFLTL ARDKHWEFSS 1690 1700 1710 1720 1730 1740 LRRSKWSTLC MLVELHTQGQ DRFVYTCNEC KHHVETRWHC TVCEDYDLCI NCYNTKSHAH 1750 1760 1770 1780 1790 1800 KMVKWGLGLD DEGSSQGEPQ SKSPQESRRL SIQRCIQSLV HACQCRNANC SLPSCQKMKR 1810 1820 1830 1840 1850 1860 VVQHTKGCKR KTNGGCPVCK QLIALCCYHA KHCQENKCPV PFCLNIKHKL RQQQIQHRLQ 1870 1880 1890 1900 1910 1920 QAQLMRRRMA TMNTRNVPQQ SLPSPTSAPP GTPTQQPSTP QTPQPPAQPQ PSPVSMSPAG 1930 1940 1950 1960 1970 1980 FPSVARTQPP TTVSTGKPTS QVPAPPPPAQ PPPAAVEAAR QIEREAQQQQ HLYRVNINNS 1990 2000 2010 2020 2030 2040 MPPGRTGMGT PGSQMAPVSL NVPRPNQVSG PVMPSMPPGQ WQQAPLPQQQ PMPGLPRPVI 2050 2060 2070 2080 2090 2100 SMQAQAAVAG PRMPSVQPPR SISPSALQDL LRTLKSPSSP QQQQQVLNIL KSNPQLMAAF 2110 2120 2130 2140 2150 2160 IKQRTAKYVA NQPGMQPQPG LQSQPGMQPQ PGMHQQPSLQ NLNAMQAGVP RPGVPPQQQA 2170 2180 2190 2200 2210 2220 MGGLNPQGQA LNIMNPGHNP NMASMNPQYR EMLRRQLLQQ QQQQQQQQQQ QQQQQQGSAG 2230 2240 2250 2260 2270 2280 MAGGMAGHGQ FQQPQGPGGY PPAMQQQQRM QQHLPLQGSS MGQMAAQMGQ LGQMGQPGLG 2290 2300 2310 2320 2330 2340 ADSTPNIQQA LQQRILQQQQ MKQQIGSPGQ PNPMSPQQHM LSGQPQASHL PGQQIATSLS 2350 2360 2370 2380 2390 2400 NQVRSPAPVQ SPRPQSQPPH SSPSPRIQPQ PSPHHVSPQT GSPHPGLAVT MASSIDQGHL 2410 2420 2430 2440 GNPEQSAMLP QLNTPSRSAL SSELSLVGDT TGDTLEKFVE GL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3)." Sobulo O.M., Borrow J., Tomek R., Reshimi S., Harden A., Schlegelberger B., Housman D., Doggett N.A., Rowley J.D., Zeleznik-Le N.J. Proc. Natl. Acad. Sci. U.S.A. 94:8732-8737(1997) [PubMed: 9238046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3." Giles R.H., Petrij F., Dauwerse H.G., den Hollander A.I., Lushnikova T., van Ommen G.J.B., Goodman R.H., Deaven L.L., Doggett N.A., Peters D.J.M., Breuning M.H. Genomics 42:96-114(1997) [PubMed: 9177780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Petrij F., den Hollander A.I., Chrivia J.C. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 1724-1725; 1789 AND 1812.
[4]	"The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein." Borrow J., Stanton V.P. Jr., Andresen J.M., Becher R., Behm F.G., Chaganti R.S.K., Civin C.I., Disteche C., Dube I., Frischauf A.M., Horsman D., Mitelman F., Volinia S., Watmore A.E., Housman D.E. Nat. Genet. 14:33-41(1996) [PubMed: 8782817] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-405, CHROMOSOMAL TRANSLOCATION WITH MYST3.
[5]	"Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13)." Panagopoulos I., Fioretos T., Isaksson M., Samuelsson U., Billstroem R., Stroembeck B., Mitelman F., Johansson B. Hum. Mol. Genet. 10:395-404(2001) [PubMed: 11157802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-83, CHROMOSOMAL TRANSLOCATION WITH MYST4.
[6]	"A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A." Yang X.-J., Ogryzko V.V., Nishikawa J., Howard B.H., Nakatani Y. Nature 382:319-324(1996) [PubMed: 8684459] [Abstract] Cited for: INTERACTION WITH PCAF.
[7]	"An essential role for p300/CBP in the cellular response to hypoxia." Arany Z., Huang L.E., Eckner R., Bhattacharya S., Jiang C., Goldberg M.A., Bunn H.F., Livingston D.M. Proc. Natl. Acad. Sci. U.S.A. 93:12969-12973(1996) [PubMed: 8917528] [Abstract] Cited for: INTERACTION WITH HIF1A AND EP300.
[8]	"Differential transcriptional activation by human T-cell leukemia virus type 1 Tax mutants is mediated by distinct interactions with CREB binding protein and p300." Bex F., Yin M.-J., Burny A., Gaynor R.B. Mol. Cell. Biol. 18:2392-2405(1998) [PubMed: 9528808] [Abstract] Cited for: INTERACTION WITH HTLV-1 TAX.
[9]	"Acetylation and modulation of erythroid Krueppel-like factor (EKLF) activity by interaction with histone acetyltransferases." Zhang W., Bieker J.J. Proc. Natl. Acad. Sci. U.S.A. 95:9855-9860(1998) [PubMed: 9707565] [Abstract] Cited for: INTERACTION WITH KLF1, FUNCTION.
[10]	"Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein." Johnston H., Kneer J., Chackalaparampil I., Yaciuk P., Chrivia J. J. Biol. Chem. 274:16370-16376(1999) [PubMed: 10347196] [Abstract] Cited for: INTERACTION WITH SRCAP.
[11]	"Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling." Doucas V., Tini M., Egan D.A., Evans R.M. Proc. Natl. Acad. Sci. U.S.A. 96:2627-2632(1999) [