Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

CREBBP (Q92793) - Overview - Molecular Target Synopsis

Protein


CREBBP, CREB-binding protein
Enzyme Classification 2.3.1.48
UniProt Q92793

Also Known as CBP_HUMAN, CREBBP, CBP

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). Found in a complex containing NCOA2; NCOA3; IKKA; IKKB and IKBKG. Probably part of a complex with HIF1A and EP300. Interacts with GATA1; the interaction results in acetylation and enhancement of transcriptional activity of GATA1. Interacts with MAF AND ZCCHC12. Interacts with DAXX; the interaction is dependent on CBP sumoylation and results in suppression of the transcriptional activity via recruitment of HDAC2 to DAXX (By similarity). Interacts with phosphorylated CREB1. Interacts with CITED4 (C-terminal region). Interacts (via the TAZ-type 1 domain) with HIF1A. Interacts with SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, DDX5, DDX17, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB and TRERF1. Interacts with KLF1; the interaction results in acetylation of KLF1 and enhancement of its transcriptional activity. Interacts with MTDH. Interacts with NFATC4. Interacts with MAFG; the interaction acetylates MAFG in the basic region and stimulates NFE2 transcriptional activity through increasing its DNA-binding activity. Interacts with IRF2; the interaction acetylates IRF2 and regulates its activity on the H4 promoter. Interacts (via N-terminus) with SS18L1/CREST (via C-terminus). Interacts with MECOM. Interacts with CITED1 (via C-terminus). Interacts with FOXO1; the interaction acetylates FOXO1 and inhibits its transcriptional activity. Interacts with NPAS2, CLOCK and ARNTL/BMAL1. Interacts with ASF1A and ASF1B; this promotes histone acetylation. Interacts with acetylated TP53/p53 and with the acetylated histones H3 and H4. Interacts (via transactivation domain and C-terminus) with PCNA; the interaction occurs on chromatin in UV-irradiated damaged cells (PubMed:24939902). Interacts with DHX9 (via N-terminus); this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation (PubMed:9323138). Interacts with SMAD4; negatively regulated by ZBTB7A (PubMed:25514493). Interacts with DUX4 (via C-terminus) (PubMed:26951377).

6FQT
CRYSTAL STRUCTURE OF CREBBP BROMODOMAIN COMPLEXD WITH DR46
RCSB/PDB
Inspect Structure
See all 3D Structures for CREBBP

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CREBBP is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: CREBBP is active in the following subcellular-locations: cytoplasm, histone acetyltransferase complex, nuclear body, nuclear chromatin, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CREBBP has gain in 0 cell-lines, loss in 3 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_5, T47D, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-74, NCI-H2595, NCI-H1651

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: MCF-7, CD20-positive B cell, CD14-positive monocyte

(see details)

3D Structures


For CREBBP there are:
108 structures (154 chains) solved
65 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

CREBBP is solved in complex with the approved drug(s):

TYL/ACETAMINOPHEN (4A9K_A, 4A9K_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CREBBP has been screened with 432 compounds (603 bioactivities), 24 compounds have bioactivities that show binding affinity of <= 500nM (35 bioactivities). (see details)