CREBBP
GeneName
CREBBP
Summary
CREBBP, also known as CBP or CREB binding protein, is a 265 kDa multifunctional protein that acts primarily as a transcriptional coactivator. It is localised in the nucleus, cytoplasm, and chromatin, and plays a pivotal role in regulating gene expression by interacting with various transcription factors, including p53 and members of the NF-kappaB family. CREBBP possesses histone acetyltransferase activity, which modifies chromatin structure to facilitate transcriptional activation. It is involved in numerous biological processes, such as the cellular response to nutrient levels, UV exposure, and the regulation of transcription by RNA polymerase II, contributing to cellular homeostasis and DNA repair mechanisms.
Importance
CREBBP is relevant to: - Cancer biology due to its role in regulating transcription factors like p53 and NF-kappaB, which are involved in cell proliferation and survival - Neurodegenerative diseases, as it has been implicated in the acetylation of tau proteins, affecting their aggregation and toxicity - Developmental processes, such as embryonic digit morphogenesis, highlighting its importance in growth and differentiation - Metabolic regulation, given its involvement in the cellular response to nutrient levels and energy homeostasis.
Top Products
For researchers investigating CREBBP, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-CREBBP antibody (ab2832), which has garnered 64 citations, reflecting its reliability in Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). This antibody is a trusted choice for those looking to study CREBBP in detail.In addition, we offer the recombinant antibody, Anti-CREBBP antibody [EPR23418-23] - ChIP Grade (ab253202). This product is particularly versatile, having been validated for use in WB, chromatin immunoprecipitation (ChIP), IHC, immunoprecipitation (IP), ICC, and flow cytometry (FC). With 11 citations, it is gaining traction in the research community and provides the batch-to-batch consistency that is characteristic of recombinant antibodies. Together, these antibodies provide robust options for studying CREBBP across multiple applications. The Recombinant Human CREBBP protein (His tag) ELISA Kit (ab198144) is an excellent option for researchers looking to study CREBBP in their experiments.
Abcam Product Citation Summary
The data indicates that CREBBP is being studied in various contexts, including long-term spatial memory retention and inflammation related to copper signalling. The use of both Western blotting and immunohistochemistry-immunofluorescence suggests a comprehensive approach to understanding the role of CREBBP in these biological processes.
Abcam Product Citation Table
Domain
The KIX domain mediates binding to HIV-1 Tat.
Function
Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). 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-BMAL1 and CLOCK-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). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493).
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, intellectual disability and a propensity for development of malignancies.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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 (PubMed:17434128). Phosphorylated by _ at Ser-124 in response to DNA damage, promoting interaction with MRE11 and lactylation of MRE11 (PubMed:38128537).
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 (PubMed:24616510). Autoacetylation is induced by glucose and fatty acids (PubMed:35675826).
Cellular localization
- Cytoplasm
- Nucleus
- Recruited to nuclear bodies by SS18L1/CREST (PubMed:15488321). In the presence of ALX1 relocalizes from the cytoplasm to the nucleus (PubMed:12929931). Relocalizes from the nucleus to the cytoplasm following UV cell damage (PubMed:15023334).
Alternative names
CBP, CREBBP, CREB-binding protein, Histone lysine acetyltransferase CREBBP, Protein lactyltransferas CREBBP, Protein-lysine acetyltransferase CREBBP
Database links
swissprot:Q92793 entrezGene:1387 omim:600140
Other research areas
- Oncology