Browse CREBBP

Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Note=Recruited to nuclear bodies by SS18L1/CREST. In the presence of ALX1 relocalizes from the cytoplasm to the nucleus.
Domain PF00439 Bromodomain
PF09030 Creb binding
PF06001 Domain of Unknown Function (DUF902)
PF08214 Histone acetylation protein
PF02172 KIX domain
PF02135 TAZ zinc finger
PF00569 Zinc finger
Function

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).

> Gene Ontology
 
Biological Process GO:0001666 response to hypoxia
GO:0001819 positive regulation of cytokine production
GO:0002218 activation of innate immune response
GO:0002220 innate immune response activating cell surface receptor signaling pathway
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006352 DNA-templated transcription, initiation
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0006473 protein acetylation
GO:0006474 N-terminal protein amino acid acetylation
GO:0006475 internal protein amino acid acetylation
GO:0007219 Notch signaling pathway
GO:0007224 smoothened signaling pathway
GO:0008589 regulation of smoothened signaling pathway
GO:0009266 response to temperature stimulus
GO:0009314 response to radiation
GO:0009408 response to heat
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0016570 histone modification
GO:0016573 histone acetylation
GO:0018076 N-terminal peptidyl-lysine acetylation
GO:0018205 peptidyl-lysine modification
GO:0018393 internal peptidyl-lysine acetylation
GO:0018394 peptidyl-lysine acetylation
GO:0030326 embryonic limb morphogenesis
GO:0031349 positive regulation of defense response
GO:0031365 N-terminal protein amino acid modification
GO:0032479 regulation of type I interferon production
GO:0032481 positive regulation of type I interferon production
GO:0032606 type I interferon production
GO:0034605 cellular response to heat
GO:0034644 cellular response to UV
GO:0035107 appendage morphogenesis
GO:0035108 limb morphogenesis
GO:0035113 embryonic appendage morphogenesis
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0042733 embryonic digit morphogenesis
GO:0043543 protein acylation
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0048511 rhythmic process
GO:0048736 appendage development
GO:0060173 limb development
GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070482 response to oxygen levels
GO:0071214 cellular response to abiotic stimulus
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071478 cellular response to radiation
GO:0071482 cellular response to light stimulus
GO:1900034 regulation of cellular response to heat
GO:1904837 beta-catenin-TCF complex assembly
Molecular Function GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0001104 RNA polymerase II transcription cofactor activity
GO:0001105 RNA polymerase II transcription coactivator activity
GO:0001159 core promoter proximal region DNA binding
GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding
GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding
GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0002039 p53 binding
GO:0003682 chromatin binding
GO:0003684 damaged DNA binding
GO:0003713 transcription coactivator activity
GO:0004402 histone acetyltransferase activity
GO:0008080 N-acetyltransferase activity
GO:0008134 transcription factor binding
GO:0016407 acetyltransferase activity
GO:0016410 N-acyltransferase activity
GO:0016746 transferase activity, transferring acyl groups
GO:0016747 transferase activity, transferring acyl groups other than amino-acyl groups
GO:0033613 activating transcription factor binding
GO:0034212 peptide N-acetyltransferase activity
GO:0043425 bHLH transcription factor binding
GO:0043426 MRF binding
GO:0061733 peptide-lysine-N-acetyltransferase activity
GO:0098811 transcriptional repressor activity, RNA polymerase II activating transcription factor binding
Cellular Component GO:0000123 histone acetyltransferase complex
GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0016604 nuclear body
GO:0031248 protein acetyltransferase complex
GO:0044454 nuclear chromosome part
GO:1902493 acetyltransferase complex
> KEGG and Reactome Pathway
 
KEGG hsa04024 cAMP signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04110 Cell cycle
hsa04310 Wnt signaling pathway
hsa04330 Notch signaling pathway
hsa04350 TGF-beta signaling pathway
hsa04520 Adherens junction
hsa04630 Jak-STAT signaling pathway
hsa04720 Long-term potentiation
hsa04916 Melanogenesis
hsa04919 Thyroid hormone signaling pathway
hsa04922 Glucagon signaling pathway
Reactome R-HSA-5619507: Activation of HOX genes during differentiation
R-HSA-5617472: Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-2426168: Activation of gene expression by SREBF (SREBP)
R-HSA-8866907: Activation of the TFAP2 (AP-2) family of transcription factors
R-HSA-3371568: Attenuation phase
R-HSA-1368108: BMAL1
R-HSA-5621481: C-type lectin receptors (CLRs)
R-HSA-5621575: CD209 (DC-SIGN) signaling
R-HSA-3371556: Cellular response to heat stress
R-HSA-2262749: Cellular response to hypoxia
R-HSA-2262752: Cellular responses to stress
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-400253: Circadian Clock
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-983231: Factors involved in megakaryocyte development and platelet production
R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism
R-HSA-201722: Formation of the beta-catenin
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-3214847: HATs acetylate histones
R-HSA-3371571: HSF1-dependent transactivation
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-3134973: LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1592230: Mitochondrial biogenesis
R-HSA-157052: NICD traffics to nucleus
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-350054: Notch-HLH transcription pathway
R-HSA-1852241: Organelle biogenesis and maintenance
R-HSA-1989781: PPARA activates gene expression
R-HSA-1912422: Pre-NOTCH Expression and Processing
R-HSA-1912408: Pre-NOTCH Transcription and Translation
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-1368082: RORA activates gene expression
R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-1655829: Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1234158: Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT
R-HSA-5633008: TP53 Regulates Transcription of Cell Death Genes
R-HSA-6803204: TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-918233: TRAF3-dependent IRF activation pathway
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-2151201: Transcriptional activation of mitochondrial biogenesis
R-HSA-8864260: Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
R-HSA-381340: Transcriptional regulation of white adipocyte differentiation
R-HSA-2032785: YAP1- and WWTR1 (TAZ)-stimulated gene expression
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CREBBP and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CREBBP and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25713363Follicular LymphomaPromote immunityThese observations therefore implicate CREBBP mutation as an early event in FL evolution that contributes to immune evasion via decreased antigen presentation.
27733359LymphomaPromote immunityHence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for CREBBP-mutant lymphomas.
28831000Diffuse Large B-Cell LymphomaPromote immunityInactivation of CREBBP expands the germinal center B cell compartment, down-regulates MHCII expression and promotes DLBCL growth. CREBBP-mutant DLBCL clones exhibited reduced histone H3 acetylation, expressed significantly less MHCII, and grew faster than wild-type clones in s.c.
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CREBBP in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CREBBP in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1060.584
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1320.931
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0850.941
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.020.963
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3530.903
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4960.897
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1680.649
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1150.947
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2120.913
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.050.965
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3350.837
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1260.0115
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CREBBP in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141714.35.98.40.576
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 414257.117.90.405
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.79.6-5.90.679
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.711.9-8.20.426
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.511.8-2.31
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.26.2160.53
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47500500.109
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CREBBP. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CREBBP. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CREBBP.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CREBBP. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CREBBP expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CREBBP and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCREBBP
NameCREB binding protein
Aliases KAT3A; RSTS; Rubinstein-Taybi syndrome; CREB-binding protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CREBBP collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting CREBBP.
ID Name Drug Type Targets #Targets
DB086559-ACETYL-2,3,4,9-TETRAHYDRO-1H-CARBAZOL-1-ONESmall MoleculeCREBBP1