Tchem CREBBP CREB-binding protein

Protein Summary

Description

Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). This gene is ubiquitously expressed and is involved in the transcriptional coactivation of many different transcription factors. First isolated as a nuclear protein that binds to cAMP-response element binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. The protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex. This protein acetylates both histone and non-histone proteins. This protein shares regions of very high sequence similarity with protein p300 in its bromodomain, cysteine-histidine-rich regions, and histone acetyltransferase domain. Mutations in this gene cause Rubinstein-Taybi syndrome (RTS). Chromosomal translocations involving this gene have been associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]

Uniprot Accession IDs

• Q92793
• D3DUC9
• O00147
• Q16376
• Q4LE28

Gene Name

• CREBBP

Ensembl ID

• ENST00000262367
• ENSP00000262367
• ENSG00000005339
• ENST00000382070
• ENSP00000371502

Symbol

• CBP
• CBP
• RSTS
• KAT3A
• MKHK1
• RSTS1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
molecular function	1
pathway	1
viral protein	1
virus	1

Protein Classes

PANTHER Classes

Protein / Transferase / Acetyltransferase / Creb-binding Protein

Protein / Transcription Factor / Transcription Cofactor / Creb-binding Protein

Protein / Nucleic Acid Binding / Dna Binding Protein / Chromatin/chromatin-binding Protein / Creb-binding Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 622.5   (req: < 5)

Gene RIFs: 242   (req: <= 3)

Antibodies: 595   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 622.5   (req: >= 5)

Gene RIFs: 242   (req: > 3)

Antibodies: 595   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 45

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 182

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (182)

Explore Active Ligands

1 – 10 of 182

CHEMBL4173488

CREBBPTchem Epigenetic

pKd : 6.24

CHEMBL4436408

CREBBPTchem Epigenetic

pIC50 : 7.19

US9458145, 1020-18

CREBBPTchem Epigenetic

pKd : 6.77

CHEMBL4171228

CREBBPTchem Epigenetic

pKd : 6.28

CHEMBL4063051

CREBBPTchem Epigenetic

pKi : 7.46

CHEMBL3786012

CREBBPTchem Epigenetic

pKi : 6.96

CHEMBL3108800

CREBBPTchem Epigenetic

pIC50 : 6.8

CHEMBL3581661

CREBBPTchem Epigenetic

pKd : 6.17

US8975417, 170

CREBBPTchem Epigenetic

pIC50 : 7.89

US8975417, 94

CREBBPTchem Epigenetic

pIC50 : 7.62

Protein-Protein Interactions (759)

Explore Interacting Targets

1 – 10 of 759

• See Interactions on String-DB

CITED1

Tbio

Novelty:  0.01956689

p_int:  0.999999991

p_ni:  9e-9

Score:  0.951

Data Source:  BioPlex,STRINGDB

CCNA2

Tchem

Novelty:  0.00049887

p_int:  0.999999071

p_ni:  9.05e-7

p_wrong:  2.4e-8

Score:  0.738

Data Source:  BioPlex,STRINGDB

C3orf62

Tdark

Novelty:  1.85670012

p_int:  0.999997224

p_ni:  0.000002759

p_wrong:  1.7e-8

Score:  0.332

Data Source:  BioPlex,STRINGDB

CDK2

Tchem

Family:  Kinase

Novelty:  0.00032118

p_int:  0.999994989

p_ni:  0.000005002

p_wrong:  9e-9

Score:  0.766

Data Source:  BioPlex,STRINGDB

CTGF

Tbio

Novelty:  0.0004346

p_int:  0.999958325

p_ni:  0.000041675

Score:  0.351

Data Source:  BioPlex,STRINGDB

TXNDC11

Tbio

Novelty:  0.07135045

p_int:  0.995742706

p_ni:  0.004255897

p_wrong:  0.000001398

Score:  0.64

Data Source:  BioPlex,STRINGDB

STAT2

Tbio

Family:  TF

Novelty:  0.00241454

p_int:  0.991141932

p_ni:  0.008857955

p_wrong:  1.14e-7

Score:  0.848

Data Source:  BioPlex,STRINGDB

CCND3

Tchem

Novelty:  0.00223085

p_int:  0.981223485

p_ni:  0.018749548

p_wrong:  0.000026967

Score:  0.839

Data Source:  BioPlex,STRINGDB

CDKN1A

Tchem

Family:  Enzyme

Novelty:  0.00033009

p_int:  0.980710644

p_ni:  0.019288073

p_wrong:  0.000001283

Score:  0.691

Data Source:  BioPlex,STRINGDB

CHURC1

Tbio

Novelty:  0.05885372

p_int:  0.765868302

p_ni:  0.233687647

p_wrong:  0.000444051

Data Source:  BioPlex

Nearest Tclin Targets (5)

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Upstream (4)

Downstream (1)

1 – 4 of 4

CALM1

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  7

1: Kaposi sarcoma-associated herpesvirus infection

2: Long-term potentiation

3: Glucagon signaling pathway

4: cAMP signaling pathway

more:  3 more common pathways

CALM2

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  7

1: Kaposi sarcoma-associated herpesvirus infection

2: Long-term potentiation

3: Glucagon signaling pathway

4: cAMP signaling pathway

more:  3 more common pathways

GSK3B

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  8

1: Kaposi sarcoma-associated herpesvirus infection

2: Cell cycle

3: Thyroid hormone signaling pathway

4: Prostate cancer

more:  4 more common pathways

CALM3

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  7

1: Kaposi sarcoma-associated herpesvirus infection

2: Long-term potentiation

3: Glucagon signaling pathway

4: cAMP signaling pathway

more:  3 more common pathways

Pathways (187)

Reactome (82)

KEGG (25)

PathwayCommons (61)

WikiPathways (19)

Activation of HOX genes during differentiation (R-HSA-5619507)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of HOX genes during differentiation	90 targets	R-HSA-5619507
Reactome	Activation of anterior HOX genes in hindbrain development during early embryogenesis	90 targets	R-HSA-5617472
Reactome	Activation of gene expression by SREBF (SREBP)	42 targets	R-HSA-2426168
Reactome	Activation of the TFAP2 (AP-2) family of transcription factors	12 targets	R-HSA-8866907
Reactome	Attenuation phase	26 targets	R-HSA-3371568

Name	Explore in Pharos	Explore in Source
Activation of HOX genes during differentiation	90 targets	R-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesis	90 targets	R-HSA-5617472
Activation of gene expression by SREBF (SREBP)	42 targets	R-HSA-2426168
Activation of the TFAP2 (AP-2) family of transcription factors	12 targets	R-HSA-8866907
Attenuation phase	26 targets	R-HSA-3371568

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (51)

Functions (15)

Components (6)

Processes (30)

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1 – 10 of 15

GO Term	Evidence	Assigned by
acetyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
damaged DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
histone acetyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
MRF binding	Inferred from Direct Assay (IDA)	UniProtKB
proximal promoter DNA-binding transcription repressor activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	BHF-UCL
proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
transcription coactivator activity	Inferred from Direct Assay (IDA)	UniProtKB
p53 binding	Inferred from Physical Interaction (IPI)	UniProtKB
RNA polymerase II transcription factor binding	Inferred from Physical Interaction (IPI)	BHF-UCL

Disease Associations (null)

No disease associations found

GWAS Traits (30)

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5

1 – 5 of 30

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	3	4	5		91.8
body mass index	EFO_0004340	8	5	11		89.2
neutrophil count	EFO_0004833	3	2	4		88.7
body height	EFO_0004339	2	2	2		87.6
leukocyte count	EFO_0004308	2	2	3		86.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 30

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	5		91.8
body mass index	EFO_0004340	11		89.2
neutrophil count	EFO_0004833	4		88.7
body height	EFO_0004339	2		87.6
leukocyte count	EFO_0004308	3		86.3

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Activator
Acyltransferase
Alternative splicing
Biological rhythms
Bromodomain
Chromosomal rearrangement
Complete proteome
Cytoplasm

GWAS Trait Find Similar Targets

No Header	No Header
anthropometric measurement
BMI-adjusted waist circumference
body fat percentage
body height
body mass index
cleft lip
Cleft palate
comparative body size at age 10, self-reported
glomerular filtration rate
glucose measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype

IDG Resources

No IDG generated resources found

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	CREB binding protein	VGNC:5745	467891
Macaque	CREB binding protein		704331
Mouse	CREB binding protein	MGI:1098280	12914
Rat	CREB binding protein	RGD:2401	54244
Dog	CREB binding protein	VGNC:39601	479866

Species	Name	OMA	EggNOG	Inparanoid
Chimp	CREB binding protein
Macaque	CREB binding protein
Mouse	CREB binding protein
Rat	CREB binding protein
Dog	CREB binding protein

Publication Statistics

PubMed Score 622.50

PubMed score by year

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PubTator Score 1717.41

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Related Publications

Text Mined References (518)

GeneRif Annotations (242)

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PMID	Year	Title