CREBBP

The KIX domain mediates binding to HIV-1 Tat.

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).

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.

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).

• 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).

CBP, CREBBP, CREB-binding protein, Histone lysine acetyltransferase CREBBP, Protein lactyltransferas CREBBP, Protein-lysine acetyltransferase CREBBP

• entrezGene:1387
• omim:600140
• swissprot:Q92793

Proteins

Epigenetics

• Oncology

265351Da