CREBBP (CREB binding protein)

2009-03-01   Cristina Gervasini 

Division of Medical Genetics, San Paolo School of Medicine, University of Milan, 20142 Milan, Italy


Atlas Image
A: CBP (16p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
B: Map showing the position of BAC clone RP11-1072J2 (UCSC Genome Browser assembly Mar 2006), centered on CREBBP gene (top) and two images of partial metaphases from normal controls showing, after FISH, CREBBP-specific signals at 16p13.3 (bottom).



The gene spans about 155 kb; transcription from centromere to telomere, number of exons: 31.


10 kb mRNA, with a 7.3 kb coding sequence, start codon in exon 1, stop codon in exon 31.



2442 amino acids; 265351 Da; predict PI=8.83; Known domains are: KIX= CREB binding , Bromo= Bromodomain, Zn=zinc-finger (corresponding to cysteine-histidine rich regions), HAT= acetyl transferasic, Q= poly Glutaminic stretch. From the carboxy to the N-terminus: Q-Zn-HAT-Zn-Bromo-KIX-Zn. Reported isoform b (2402 aa) lacking aa406-444 (exon 5). Methylation of the KIX domain by CARM1 blocks association with CREB. Phosphorylated upon DNA damage, probably by ATM or ATR.


Wide expression; expression in the whole embryo as well brain; cDNA sources: mammary gland; lung; placenta; testis; lymph node; thymus; mouth; ear; kidney; embryonic tissue; larynx; pancreas; intestine; blood; heart; amniotic fluid; trachea; liver; thyroid; skin; connective tissue; uterus; eye; prostate; stomach; ovary; salivary gland; muscle; adrenal gland; bone marrow; adipose tissue; spleen; nerve; bone; bladder.




Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes;
Acts as transcription co-activator by: i) enabling the interaction between different TF and RNAPolII complexes, ii) serving as molecular scaffold that brings enzymes to the promoter, iii) remodelling the chromatin favouring the open status, by histone and non-histone proteins acetylation.
Essential role in embryogenesis, cell differentiation, apoptosis, and proliferation;
Involved in the regulation of cell cycle during G1/S transition.


Implicated in

Entity name
Poor: remission is obtained in half cases; survival is often less than 1yr.
+8 as an additional anomalies in half cases.
Hybrid gene
5 MOZ - 3 CBP.
Fusion protein
N-term finger motifs and acetyl transferase from MOZ fused to most of CBP, with a breakpoint in 5 of the CREB binding domain of CBP.
Entity name
Acute myeloid leukaemia (AML) M4/M5a and therapy-related myelodysplastic syndromes (MDS). Only 4 cases described.
Poor, bad response to chemotherapy.
Hybrid gene
5 MYST4 - 3 CBP.
Fusion protein
In-frame fusion between MYST4 exon 17 and CREBBP exon 3. Variants fusing MYST4 exon 16 and CREBBP exon 5; MYST4 exon 17 and CREBBP exon 7 have been also described. CREBBP-MYST4 transcripts have been detected.
Entity name
Therapy related AML (t-AML); should be very close to the t(11;22)(q23;q13).
Likely to be poor.
Hybrid gene
5 MLL - 3CBP.
Fusion protein
N-term AT hook and DNA methyltransferase from MLL fused to most of CBP; variable brakpoint in CBP: either 5 to the CREB binding domain (like in the t(8;16)), or just upstream the bromodomain.
Entity name
Rubinstein-Taybi syndrome
Due to CBP haploinsufficiency.
Rare autosomal dominant congenital disorder characterized by postnatal growth retardation and psychomotor developmental delay, skeletal anomalies (broad and duplicated distal phalanges of thumbs and halluces are a landmark sign) and specific facial dysmorphisms. The latter include down-slanted palpebral fissures, broad nasal bridge, beaked nose and micrognathia. In addition, patients with RSTS have an increased, although not well documented, risk of tumor formation.
Atlas Image
Top: Ideogram of chromosome 16 and chromosomal localisation of the CREBBP gene. Middle: the genomic region including CREBBP (red) and flanking genes is zoomed. Deletions spanning CREBBP and adjacent sequences (accounting for about 10% of CREBBP mutations) are indicated by black lines. Mosaic deletions (only 3 so far detected) are asterisked; dotted lines target low-resolution mapped breakpoints. So far 22 deletions have been reported and the differently sized ones (21) are here diagrammed.
Bottom: structure of CREBBP gene and protein. Different colours are used to link gene exons (pictured by rectangles) and corresponding protein domains. Different reported point mutations (n.108 in Leiden Open Variation Database) are shown: filled circles (nonsense) and dotted circles (frameshift), squares (missense) and triangles (splicing). Most mutations cluster to exons encoding the HAT domain.
Known domains from the carbossi-terminal are: Q= poly Glutaminic stretch, Zn=zinc-finger, HAT= acetyl transferasic, Bromo= Bromodomain, KIX= CREB binding).


Atlas Image
Atlas Image
Localization of breakpoints affecting CREBBP and partner genes in leukaemia-associated balanced translocations.


Pubmed IDLast YearTitleAuthors
108288852000CBP/p300 histone acetyl-transferase activity is important for the G1/S transition.Ait-Si-Ali S et al
152072392004Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration.Alarcón JM et al
129090862003Ca(2+)/CREB/CBP-dependent gene regulation: a shared mechanism critical in long-term synaptic plasticity and neuronal survival.Bito H et al
119276402002CBP and p300: versatile coregulators with important roles in hematopoietic gene expression.Blobel GA et al
87828171996The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.Borrow J et al
127475482003The multifunctional role of E1A in the transcriptional regulation of CREB/CBP-dependent target genes.Brockmann D et al
89603681996p300 and CBP as transcriptional regulators and targets of oncogenic events.Eckner R et al
178550482007High frequency of mosaic CREBBP deletions in Rubinstein-Taybi syndrome patients and mapping of somatic and germ-line breakpoints.Gervasini C et al
91777801997Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3.Giles RH et al
104973011999p300 and CBP: partners for life and death.Giordano A et al
92388491997The multifunctional role of the co-activator CBP in transcriptional regulation.Goldman PS et al
113584912001p300/CBP/p53 interaction and regulation of the p53 response.Grossman SR et al
168685632006Rubinstein-Taybi syndrome.Hennekam RC et al
119627652002The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease.Janknecht R et al
153134122004CBP and p300: HATs for different occasions.Kalkhoven E et al
174102092007CBP/p300 are bimodal regulators of Wnt signaling.Li J et al
182730212008The structural basis of protein acetylation by the p300/CBP transcriptional coactivator.Liu X et al
121685672002Transcriptional control of the inflammatory response: a role for the CREB-binding protein (CBP).Matt T et al
114677392001CBP, a transcriptional coactivator and acetyltransferase.McManus KJ et al
106100211999Developmentally regulated expression of the transcriptional cofactors/histone acetyltransferases CBP and p300 during mouse embryogenesis.Partanen A et al
153134132004Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders.Rouaux C et al
92380461997MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3).Sobulo OM et al
91668311997The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene.Taki T et al
174841312007Aberrant forms of histone acetyltransferases in human disease.Van Beekum O et al
112792242001CREB-binding protein and p300 in transcriptional regulation.Vo N et al
186578482008t(8;16)(p11;p13) predisposes to a transient but potentially recurring neonatal leukemia.Wong KF et al
105238501999Function for p300 and not CBP in the apoptotic response to DNA damage.Yuan ZM et al

Other Information

Locus ID:

NCBI: 1387
MIM: 600140
HGNC: 2348
Ensembl: ENSG00000005339


dbSNP: 1387
ClinVar: 1387
TCGA: ENSG00000005339


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell cycleKEGGko04110
Wnt signaling pathwayKEGGko04310
Notch signaling pathwayKEGGko04330
TGF-beta signaling pathwayKEGGko04350
Adherens junctionKEGGko04520
Jak-STAT signaling pathwayKEGGko04630
Long-term potentiationKEGGko04720
Huntington's diseaseKEGGko05016
Renal cell carcinomaKEGGko05211
Prostate cancerKEGGko05215
Cell cycleKEGGhsa04110
Wnt signaling pathwayKEGGhsa04310
Notch signaling pathwayKEGGhsa04330
TGF-beta signaling pathwayKEGGhsa04350
Adherens junctionKEGGhsa04520
Jak-STAT signaling pathwayKEGGhsa04630
Long-term potentiationKEGGhsa04720
Huntington's diseaseKEGGhsa05016
Pathways in cancerKEGGhsa05200
Renal cell carcinomaKEGGhsa05211
Prostate cancerKEGGhsa05215
Influenza AKEGGko05164
Influenza AKEGGhsa05164
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
Hepatitis BKEGGhsa05161
HIF-1 signaling pathwayKEGGhsa04066
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
FoxO signaling pathwayKEGGhsa04068
Thyroid hormone signaling pathwayKEGGhsa04919
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Glucagon signaling pathwayKEGGhsa04922
Glucagon signaling pathwayKEGGko04922
Organelle biogenesis and maintenanceREACTOMER-HSA-1852241
Mitochondrial biogenesisREACTOMER-HSA-1592230
Transcriptional activation of mitochondrial biogenesisREACTOMER-HSA-2151201
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by NOTCH1 in CancerREACTOMER-HSA-2644603
Signaling by NOTCH1 PEST Domain Mutants in CancerREACTOMER-HSA-2644602
Constitutive Signaling by NOTCH1 PEST Domain MutantsREACTOMER-HSA-2644606
Signaling by NOTCH1 HD+PEST Domain Mutants in CancerREACTOMER-HSA-2894858
Constitutive Signaling by NOTCH1 HD+PEST Domain MutantsREACTOMER-HSA-2894862
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathwaysREACTOMER-HSA-168928
TRAF3-dependent IRF activation pathwayREACTOMER-HSA-918233
TRAF6 mediated IRF7 activationREACTOMER-HSA-933541
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN productionREACTOMER-HSA-3134973
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CD209 (DC-SIGN) signalingREACTOMER-HSA-5621575
Factors involved in megakaryocyte development and platelet productionREACTOMER-HSA-983231
Signal TransductionREACTOMER-HSA-162582
Signaling by NOTCHREACTOMER-HSA-157118
Pre-NOTCH Expression and ProcessingREACTOMER-HSA-1912422
Pre-NOTCH Transcription and TranslationREACTOMER-HSA-1912408
Signaling by NOTCH1REACTOMER-HSA-1980143
NOTCH1 Intracellular Domain Regulates TranscriptionREACTOMER-HSA-2122947
Signaling by WntREACTOMER-HSA-195721
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Formation of the beta-catenin:TCF transactivating complexREACTOMER-HSA-201722
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Notch-HLH transcription pathwayREACTOMER-HSA-350054
YAP1- and WWTR1 (TAZ)-stimulated gene expressionREACTOMER-HSA-2032785
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Circadian ClockREACTOMER-HSA-400253
BMAL1:CLOCK,NPAS2 activates circadian gene expressionREACTOMER-HSA-1368108
RORA activates gene expressionREACTOMER-HSA-1368082
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Fatty acid, triacylglycerol, and ketone body metabolismREACTOMER-HSA-535734
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)REACTOMER-HSA-400206
PPARA activates gene expressionREACTOMER-HSA-1989781
Regulation of cholesterol biosynthesis by SREBP (SREBF)REACTOMER-HSA-1655829
Activation of gene expression by SREBF (SREBP)REACTOMER-HSA-2426168
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of white adipocyte differentiationREACTOMER-HSA-381340
Cellular responses to stressREACTOMER-HSA-2262752
Cellular response to hypoxiaREACTOMER-HSA-2262749
Regulation of Hypoxia-inducible Factor (HIF) by oxygenREACTOMER-HSA-1234174
Regulation of gene expression by Hypoxia-inducible FactorREACTOMER-HSA-1234158
Cellular response to heat stressREACTOMER-HSA-3371556
HSF1-dependent transactivationREACTOMER-HSA-3371571
Attenuation phaseREACTOMER-HSA-3371568
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
HATs acetylate histonesREACTOMER-HSA-3214847
Activation of HOX genes during differentiationREACTOMER-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesisREACTOMER-HSA-5617472
TP53 Regulates Transcription of Cell Death GenesREACTOMER-HSA-5633008
TP53 Regulates Transcription of Genes Involved in Cytochrome C ReleaseREACTOMER-HSA-6803204
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factorsREACTOMER-HSA-8864260
Activation of the TFAP2 (AP-2) family of transcription factorsREACTOMER-HSA-8866907

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
213901262011Inactivating mutations of acetyltransferase genes in B-cell lymphoma.301
192706802009CBP/p300-mediated acetylation of histone H3 on lysine 56.286
213901302011CREBBP mutations in relapsed acute lymphoblastic leukaemia.233
164767422006Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase.177
157356822005HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas.130
185528332008Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis.121
174687672007SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes.116
147593702004Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation.114
157064852005Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.114
174341282007Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB.103


Cristina Gervasini

CREBBP (CREB binding protein)

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

Online version:

Historical Card

2000-07-01 CREBBP (CREB binding protein) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France