CREBBP

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]

Full Name

CREB binding protein

Function

Acetylates histones, giving a specific tag for transcriptional activation (PubMed:24616510).

Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:9707565, PubMed:24207024, PubMed:28790157, PubMed:30540930).

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 (PubMed:14645221).

Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902).

Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024).

Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157).

Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930).

Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493).

Biological Process

Beta-catenin-TCF complex assembly Source: Reactome
Cellular response to UV Source: UniProtKB
Embryonic digit morphogenesis Source: BHF-UCL
Histone acetylation Source: UniProtKB
Histone glutamine methylation Source: UniProtKB
Homeostatic process Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Notch signaling pathway Source: Reactome
N-terminal peptidyl-lysine acetylation Source: UniProtKB
Positive regulation of Notch signaling pathway Source: Reactome
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: HGNC-UCL
Positive regulation of transcription of Notch receptor target Source: Reactome
Positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
Positive regulation of type I interferon production Source: Reactome
Protein acetylation Source: UniProtKB
Protein-containing complex assembly Source: ProtInc
Protein destabilization Source: UniProtKB
Regulation of apoptotic process Source: Reactome
Regulation of cellular response to heat Source: Reactome
Regulation of lipid metabolic process Source: Reactome
Regulation of myeloid cell differentiation Source: Reactome
Regulation of smoothened signaling pathway Source: BHF-UCL
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
Response to hypoxia Source: UniProtKB
Rhythmic process Source: UniProtKB-KW
Signal transduction Source: ProtInc
Stimulatory C-type lectin receptor signaling pathway Source: Reactome
Transcription initiation from RNA polymerase II promoter Source: Reactome
Viral process Source: UniProtKB-KW

Cellular Location

Nucleus; Cytoplasm. Recruited to nuclear bodies by SS18L1/CREST. In the presence of ALX1 relocalizes from the cytoplasm to the nucleus.

Involvement in disease

Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with KMT2A/MLL1; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.
Rubinstein-Taybi syndrome 1 (RSTS1):
A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.
Menke-Hennekam syndrome 1 (MKHK1):
A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum.

PTM

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 (By similarity).
Phosphorylated by CHUK/IKKA at Ser-1382 and Ser-1386; these phosphorylations promote cell growth by switching the binding preference of CREBBP from TP53 to NF-kappa-B.
Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX.
Autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53.