Protein / target

CREB-binding protein

Encoded byCREBBPQ92793Homo sapiensSwiss-Prot

UniProt: Q92793 Ensembl: ENSG00000005339 HGNC: HGNC:2348 NCBI Gene: 1387

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Peptide lactyltransferase (CoA-dependent)

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene CREBBP · Genetic evidence · score 0.90

Therapeutic position

Clinically advancing target

Research activity

Emerging research

2 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Acetylates histones, giving a specific tag for transcriptional activation.

View complete UniProt function annotation

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)

Subcellular location

CytoplasmNucleus

Domains and Gene Ontology detail (52)

Domains & features

KIXBromoCBP/p300-type HAT

Gene Ontology

Cchromatin
Ccytoplasm
Ccytosol
Chistone acetyltransferase complex
Cnuclear body
Cnucleoplasm
Cnucleus
Ctranscription regulator complex
Facetyltransferase activity
Fchromatin binding
Fchromatin DNA binding
Fdamaged DNA binding

2442 aa · 265 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Transcriptional regulationUniProt · GOMetabolic enzyme activityGO

View supporting evidence

Transcriptional regulation

·Acetylates histones, giving a specific tag for transcriptional activation (PubMed:211319…
·transcription regulator complex
·DNA-binding transcription factor binding
·RNA polymerase II-specific DNA-binding transcription factor binding

Metabolic enzyme activity

·acetyltransferase activity
·histone acetyltransferase activity
·histone H3K18 acetyltransferase activity
·histone H3K27 acetyltransferase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CREBBP

Gene-level evidence surfaced through the gene CREBBPthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Genetic Diseases, Inborn

0.90Well supported

Genetic evidence dominant · Open Targets 0.55

Urinary Bladder Neoplasms

0.60Moderately supported

Somatic mutation evidence dominant · Open Targets 0.54

Lymphoma, Large B-Cell, Diffuse

0.57Moderately supported

Somatic mutation evidence dominant · Open Targets 0.65

Neoplasms

0.46Preliminary

Pathway evidence dominant · Open Targets 0.60 · no direct causal or clinical evidence

Precursor Cell Lymphoblastic Leukemia-Lymphoma

0.46Limited support

Somatic mutation evidence dominant · Open Targets 0.45

View evidence synthesis (5)

Genetic Diseases, InbornWell supported

0.90

agreement 0.76–1.00

Genetic99%Literature1%

Open Targets aggregate 0.55 · 2 independent evidence families

Urinary Bladder NeoplasmsModerately supported

0.60

agreement 0.44–0.76

Somatic mutation85%Literature15%

Open Targets aggregate 0.54 · 2 independent evidence families

Lymphoma, Large B-Cell, DiffuseModerately supported

0.57

agreement 0.41–0.73

Somatic mutation79%Literature21%

Open Targets aggregate 0.65 · 2 independent evidence families

NeoplasmsPreliminary

0.46

agreement 0.28–0.64

Pathway74%Literature26%

Open Targets aggregate 0.60 · 2 independent evidence families · no direct causal or clinical evidence

Precursor Cell Lymphoblastic Leukemia-LymphomaLimited support

0.46

agreement 0.29–0.62

Somatic mutation74%Literature26%

Open Targets aggregate 0.45 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Lymphoma, Large B-Cell, Diffuse0.65

Neoplasms0.60

Genetic Diseases, Inborn0.55

Urinary Bladder Neoplasms0.54

Precursor Cell Lymphoblastic Leukemia-Lymphoma0.45

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)

PRI-724Phase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (9)

SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation.642 cites

Vecsey CG · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007

Evolutionary trajectories of small cell lung cancer under therapy.84 cites

George J · Nature · 2024

Recent

Evolutionary trajectories of small cell lung cancer under therapy.

George J · Nature · 2024

Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation.

Vecsey CG · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007

Europe PMC papers linked directly to this protein.