Reviewed, UniProtKB/Swiss-Prot P45481 (CBP_MOUSE)

Names and origin

Protein names

Recommended name:
    CREB-binding protein
    EC=2.3.1.48

Gene names

Name:	Crebbp
Synonyms:	Cbp

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	2441 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 By similarity.
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, TRERF1 and ZCCHC12. Interacts with KLF1; the interaction results in acetylation and enhancement of transcriptional activity of KLF1 By similarity.
Subcellular location	Nucleus.
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. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity.
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	Transcription Transcription regulation
Cellular component	Nucleus
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 sequence or structural similarity. Source: UniProtKB germ-line stem cell maintenance Inferred from mutant phenotype. Source: MGI histone acetylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription factor activity Traceable author statement. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI
Cellular component	histone acetyltransferase complex Inferred from direct assay. Source: MGI outer kinetochore of condensed chromosome Inferred from direct assay. Source: MGI transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	DNA binding Inferred from direct assay. Source: MGI MyoD binding Inferred from sequence or structural similarity. Source: UniProtKB histone acetyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB transcription coactivator activity Traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P88946	4	EBI-296306,EBI-936023	From a different organism.
CREB1	P16220	1	EBI-296306,EBI-711855	From a different organism.
Khdrbs1	Q60749	3	EBI-296306,EBI-519077
MYB	P10242	1	EBI-296306,EBI-298355	From a different organism.
Rela	Q04207	1	EBI-296306,EBI-644400
SREBF1	P36956-1	1	EBI-296306,EBI-948328	From a different organism.
TP53	P04637	2	EBI-296306,EBI-366083	From a different organism.
Trp53	Q64451	1	EBI-296306,EBI-493476
Wwtr1	Q9EPK5	1	EBI-296306,EBI-1211920

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2441

2441

CREB-binding protein

PRO_0000211191

Regions

Domain

586 – 665

80

KIX

Domain

1104 – 1176

73

Bromo

Zinc finger

346 – 432

87

TAZ-type 1

Zinc finger

1702 – 1745

44

ZZ-type

Zinc finger

1766 – 1847

82

TAZ-type 2

Region

226 – 409

184

Interaction with SRCAP By similarity

Compositional bias

1062 – 1065

4

Poly-Glu

Compositional bias

1556 – 1563

8

Poly-Glu

Compositional bias

1944 – 1949

6

Poly-Pro

Compositional bias

1968 – 1971

4

Poly-Gln

Compositional bias

2082 – 2086

5

Poly-Gln

Compositional bias

2200 – 2216

17

Poly-Gln

Compositional bias

2296 – 2299

4

Poly-Gln

Amino acid modifications

Modified residue

120

1

Phosphoserine By similarity

Modified residue

600

1

Omega-N-methylated arginine Probable

Modified residue

624

1

Omega-N-methylated arginine Probable

Modified residue

1031

1

Phosphoserine By similarity

Modified residue

1073

1

Phosphoserine By similarity

Modified residue

1589

1

N6-acetyllysine By similarity

Modified residue

1592

1

N6-acetyllysine By similarity

Modified residue

1593

1

N6-acetyllysine By similarity

Modified residue

1596

1

N6-acetyllysine By similarity

Modified residue

1598

1

N6-acetyllysine By similarity

Modified residue

1756

1

Phosphoserine By similarity

Modified residue

2064

1

Phosphoserine By similarity

Modified residue

2077

1

Phosphoserine By similarity

Modified residue

2080

1

Phosphoserine By similarity

Experimental info

Mutagenesis

600

1

R → N: Abolishes binding to CREB

Secondary structure

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2441

Helix Strand Turn

Details...

Helix

347 – 372

26

Helix

384 – 396

13

Helix

400 – 402

3

Helix

406 – 420

15

Helix

429 – 433

5

Turn

587 – 590

4

Helix

591 – 594

4

Helix

597 – 611

15

Helix

617 – 621

5

Helix

623 – 640

18

Helix

646 – 662

17

Turn

663 – 665

3

Turn

667 – 671

5

Turn

1709 – 1711

3

Beta strand

1713 – 1726

14

Helix

1731 – 1737

7

Beta strand

1741 – 1746

6

Helix

1765 – 1785

21

Helix

1794 – 1808

15

Helix

1812 – 1815

4

Helix

1818 – 1833

16

Helix

1844 – 1849

6

Beta strand

2061 – 2064

4

Helix

2068 – 2075

8

Beta strand

2076 – 2079

4

Helix

2088 – 2091

4

Helix

2097 – 2100

4

Helix

2102 – 2104

3

Beta strand

2106 – 2108

3

Sequences

	Sequence		Length	Mass (Da)
	P45481-1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 0ABB028C3112F419	FASTA	2,441	265,474
	10 20 30 40 50 60 MAENLLDGPP NPKRAKLSSP GFSANDNTDF GSLFDLENDL PDELIPNGEL SLLNSGNLVP 70 80 90 100 110 120 DAASKHKQLS ELLRGGSGSS INPGIGNVSA SSPVQQGLGG QAQGQPNSTN MASLGAMGKS 130 140 150 160 170 180 PLNQGDSSTP NLPKQAASTS GPTPPASQAL NPQAQKQVGL VTSSPATSQT GPGICMNANF 190 200 210 220 230 240 NQTHPGLLNS NSGHSLMNQA QQGQAQVMNG SLGAAGRGRG AGMPYPAPAM QGATSSVLAE 250 260 270 280 290 300 TLTQVSPQMA GHAGLNTAQA GGMTKMGMTG TTSPFGQPFS QTGGQQMGAT GVNPQLASKQ 310 320 330 340 350 360 SMVNSLPAFP TDIKNTSVTT VPNMSQLQTS VGIVPTQAIA TGPTADPEKR KLIQQQLVLL 370 380 390 400 410 420 LHAHKCQRRE QANGEVRACS LPHCRTMKNV LNHMTHCQAP KACQVAHCAS SRQIISHWKN 430 440 450 460 470 480 CTRHDCPVCL PLKNASDKRN QQTILGSPAS GIQNTIGSVG AGQQNATSLS NPNPIDPSSM 490 500 510 520 530 540 QRAYAALGLP YMNQPQTQLQ PQVPGQQPAQ PPAHQQMRTL NALGNNPMSV PAGGITTDQQ 550 560 570 580 590 600 PPNLISESAL PTSLGATNPL MNDGSNSGNI GSLSTIPTAA PPSSTGVRKG WHEHVTQDLR 610 620 630 640 650 660 SHLVHKLVQA IFPTPDPAAL KDRRMENLVA YAKKVEGDMY ESANSRDEYY HLLAEKIYKI 670 680 690 700 710 720 QKELEEKRRT RLHKQGILGN QPALPASGAQ PPVIPPAQSV RPPNGPLPLP VNRMQVSQGM 730 740 750 760 770 780 NSFNPMSLGN VQLPQAPMGP RAASPMNHSV QMNSMASVPG MAISPSRMPQ PPNMMGTHAN 790 800 810 820 830 840 NIMAQAPTQN QFLPQNQFPS SSGAMSVNSV GMGQPAAQAG VSQGQEPGAA LPNPLNMLAP 850 860 870 880 890 900 QASQLPCPPV TQSPLHPTPP PASTAAGMPS LQHPTAPGMT PPQPAAPTQP STPVSSGQTP 910 920 930 940 950 960 TPTPGSVPSA AQTQSTPTVQ AAAQAQVTPQ PQTPVQPPSV ATPQSSQQQP TPVHTQPPGT 970 980 990 1000 1010 1020 PLSQAAASID NRVPTPSTVT SAETSSQQPG PDVPMLEMKT EVQTDDAEPE PTESKGEPRS 1030 1040 1050 1060 1070 1080 EMMEEDLQGS SQVKEETDTT EQKSEPMEVE EKKPEVKVEA KEEEENSSND TASQSTSPSQ 1090 1100 1110 1120 1130 1140 PRKKIFKPEE LRQALMPTLE ALYRQDPESL PFRQPVDPQL LGIPDYFDIV KNPMDLSTIK 1150 1160 1170 1180 1190 1200 RKLDTGQYQE PWQYVDDVRL MFNNAWLYNR KTSRVYKFCS KLAEVFEQEI DPVMQSLGYC 1210 1220 1230 1240 1250 1260 CGRKYEFSPQ TLCCYGKQLC TIPRDAAYYS YQNRYHFCGK CFTEIQGENV TLGDDPSQPQ 1270 1280 1290 1300 1310 1320 TTISKDQFEK KKNDTLDPEP FVDCKECGRK MHQICVLHYD IIWPSGFVCD NCLKKTGRPR 1330 1340 1350 1360 1370 1380 KENKFSAKRL QTTRLGNHLE DRVNKFLRRQ NHPEAGEVFV RVVASSDKTV EVKPGMKSRF 1390 1400 1410 1420 1430 1440 VDSGEMSESF PYRTKALFAF EEIDGVDVCF FGMHVQDTAL IAPHQIQGCV YISYLDSIHF 1450 1460 1470 1480 1490 1500 FRPRCLRTAV YHEILIGYLE YVKKLVYVTA HIWACPPSEG DDYIFHCHPP DQKIPKPKRL 1510 1520 1530 1540 1550 1560 QEWYKKMLDK AFAERIINDY KDIFKQANED RLTSAKELPY FEGDFWPNVL EESIKELEQE 1570 1580 1590 1600 1610 1620 EEERKKEEST AASETPEGSQ GDSKNAKKKN NKKTNKNKSS ISRANKKKPS MPNVSNDLSQ 1630 1640 1650 1660 1670 1680 KLYATMEKHK EVFFVIHLHA GPVISTQPPI VDPDPLLSCD LMDGRDAFLT LARDKHWEFS 1690 1700 1710 1720 1730 1740 SLRRSKWSTL CMLVELHTQG QDRFVYTCNE CKHHVETRWH CTVCEDYDLC INCYNTKSHT 1750 1760 1770 1780 1790 1800 HKMVKWGLGL DDEGSSQGEP QSKSPQESRR LSIQRCIQSL VHACQCRNAN CSLPSCQKMK 1810 1820 1830 1840 1850 1860 RVVQHTKGCK RKTNGGCPVC KQLIALCCYH AKHCQENKCP VPFCLNIKHN VRQQQIQHCL 1870 1880 1890 1900 1910 1920 QQAQLMRRRM ATMNTRNVPQ QSLPSPTSAP PGTPTQQPST PQTPQPPAQP QPSPVNMSPA 1930 1940 1950 1960 1970 1980 GFPNVARTQP PTIVSAGKPT NQVPAPPPPA QPPPAAVEAA RQIEREAQQQ QHLYRANINN 1990 2000 2010 2020 2030 2040 GMPPGRDGMG TPGSQMTPVG LNVPRPNQVS GPVMSSMPPG QWQQAPIPQQ QPMPGMPRPV 2050 2060 2070 2080 2090 2100 MSMQAQAAVA GPRMPNVQPN RSISPSALQD LLRTLKSPSS PQQQQQVLNI LKSNPQLMAA 2110 2120 2130 2140 2150 2160 FIKQRTAKYV ANQPGMQPQP GLQSQPGMQP QPGMHQQPSL QNLNAMQAGV PRPGVPPPQP 2170 2180 2190 2200 2210 2220 AMGGLNPQGQ ALNIMNPGHN PNMTNMNPQY REMVRRQLLQ HQQQQQQQQQ QQQQQQNSAS 2230 2240 2250 2260 2270 2280 LAGGMAGHSQ FQQPQGPGGY APAMQQQRMQ QHLPIQGSSM GQMAAPMGQL GQMGQPGLGA 2290 2300 2310 2320 2330 2340 DSTPNIQQAL QQRILQQQQM KQQIGSPGQP NPMSPQQHML SGQPQASHLP GQQIATSLSN 2350 2360 2370 2380 2390 2400 QVRSPAPVQS PRPQSQPPHS SPSPRIQPQP SPHHVSPQTG TPHPGLAVTM ASSMDQGHLG 2410 2420 2430 2440 NPEQSAMLPQ LNTPNRSALS SELSLVGDTT GDTLEKFVEG L

References

[1]	"Phosphorylated CREB binds specifically to the nuclear protein CBP." Chrivia J.C., Kwok R.P.S., Lamb N., Hagiwara M., Montminy M.R., Goodman R.H. Nature 365:855-859(1993) [PubMed: 8413673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors." Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S.-C., Heyman R.A., Rose D.W., Glass C.K., Rosenfeld M.G. Cell 85:403-414(1996) [PubMed: 8616895] [Abstract] Cited for: INTERACTION WITH NCOA1.
[3]	"Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism." Parker D., Ferreri K., Nakajima T., LaMorte V.J., Evans R., Koerber S.C., Hoeger C., Montminy M.R. Mol. Cell. Biol. 16:694-703(1996) [PubMed: 8552098] [Abstract] Cited for: INTERACTION WITH CREB1, MUTAGENESIS OF ARG-600.
[4]	"The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function." Torchia J., Rose D.W., Inostroza J., Kamei Y., Westin S., Glass C.K., Rosenfeld M.G. Nature 387:677-684(1997) [PubMed: 9192892] [Abstract] Cited for: INTERACTION WITH NCOA3.
[5]	"A transcriptional switch mediated by cofactor methylation." Xu W., Chen H., Du K., Asahara H., Tini M., Emerson B.M., Montminy M., Evans R.M. Science 294:2507-2511(2001) [PubMed: 11701890] [Abstract] Cited for: INTERACTION WITH CARM1, METHYLATION AT ARG-600 AND ARG-624, FUNCTION.
[6]	"Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: induced expression in mammary epithelial cells." Yahata T., Takedatsu H., Dunwoodie S.L., Braganca J., Swingler T., Withington S.L., Hur J., Coser K.R., Isselbacher K.J., Bhattacharya S., Shioda T. Genomics 80:601-613(2002) [PubMed: 12504852] [Abstract] Cited for: INTERACTION WITH CITED4.
[7]	"Sizn1 is a novel protein that functions as a transcriptional coactivator of bone morphogenic protein signaling." Cho G., Lim Y., Zand D., Golden J.A. Mol. Cell. Biol. 28:1565-1572(2008) [PubMed: 18160706] [Abstract] Cited for: INTERACTION WITH ZCCHC12.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

S66385 mRNA. Translation: AAB28651.1.

PIR

S39161.

UniGene

Mm.132238
Mm.392384

3D structure databases

PDBMSD

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Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F81	NMR	-	A	1764-1849	[»]
1JJS	NMR	-	A	2067-2112	[»]
1KBH	NMR	-	B	2059-2117	[»]
1KDX	NMR	-	A	586-666	[»]
1L8C	NMR	-	A	345-439	[»]