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Protein / target

Pituitary adenylate cyclase-activating polypeptide

Encoded byADCYAP1P18509Homo sapiensSwiss-Prot
UniProt: P18509Ensembl: ENSG00000141433HGNC: HGNC:241NCBI Gene: 116
Small-molecule tractable
Druggability
Structure with Ligand
2
Research papers

Protein at a glance

Biological role

Pituitary adenylate cyclase activating polypeptide

Strongest disease association

Alcohol drinking

Via encoding gene ADCYAP1 · Genetic evidence · score 0.54

Research activity

Emerging research

2 papers · latest 2025

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

PACAP is a neuropeptide involved in diverse array of physiological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors: VIP receptor 1 (VIPR1), VIP receptor 2 (VIPR2), and PACAP type I receptor (ADCYAP1R1).

View complete UniProt function annotation

PACAP is a neuropeptide involved in diverse array of physiological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors: VIP receptor 1 (VIPR1), VIP receptor 2 (VIPR2), and PACAP type I receptor (ADCYAP1R1) (PubMed:11175907, PubMed:23800469, PubMed:32047270, PubMed:32004469, PubMed:36385145). Exerts neuroprotective and general cytoprotective effects due to anti-apoptotic, anti-inflammatory, and antioxidant actions (PubMed:23800469). Promotes neuron projection development through the RAPGEF2/Rap1/B-Raf/ERK pathway (PubMed:23800469). In chromaffin cells, induces long-lasting increase of intracellular calcium concentrations and neuroendocrine secretion (By similarity). Involved in the control of glucose homeostasis, induces insulin secretion by pancreatic beta cells (By similarity). PACAP exists in two bioactive forms from proteolysis of the same precursor protein, PACAP27 and PACAP38, which differ by eleven amino acid residues in the C-terminus (PubMed:32047270, PubMed:32004469)

Subcellular location

Secreted
Domains and Gene Ontology detail (29)

Gene Ontology

  • Cextracellular region
  • Cextracellular space
  • Cneuron projection
  • Cperikaryon
  • Fneuropeptide hormone activity
  • Fpeptide hormone receptor binding
  • Fpituitary adenylate cyclase activating polypeptide activity
  • Fsignaling receptor binding
  • Ftype 1 vasoactive intestinal polypeptide receptor binding
  • Ftype 2 vasoactive intestinal polypeptide receptor binding
  • Pactivation of adenylate cyclase activity
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway

176 aa · 19 kDa

Biological roles

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

G protein-coupled signallingUniProt · GO
View supporting evidence

G protein-coupled signalling

  • ·PACAP is a neuropeptide involved in diverse array of physiological processes through act…
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  • ·regulation of G protein-coupled receptor signaling pathway

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 ADCYAP1

Gene-level evidence surfaced through the gene ADCYAP1that 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.

Alcohol drinking
0.54Moderately supported

Genetic evidence dominant · Open Targets 0.33

Aortic Diseases
0.51Moderately supported

Genetic evidence dominant · Open Targets 0.31

Restless Legs Syndrome
0.50Moderately supported

Genetic evidence dominant · Open Targets 0.30

Obesity disorder
0.41Limited support

Genetic evidence dominant · Open Targets 0.24

Diabetes Mellitus, Type 1
0.36Limited support

Genetic evidence dominant · Open Targets 0.22

View evidence synthesis (5)
Alcohol drinkingModerately supported
0.54
agreement 0.40–0.68
Genetic99%Literature1%

Open Targets aggregate 0.33 · 2 independent evidence families

Aortic DiseasesModerately supported
0.51
agreement 0.39–0.63
Genetic100%

Open Targets aggregate 0.31 · 1 independent evidence family

Restless Legs SyndromeModerately supported
0.50
agreement 0.38–0.62
Genetic100%

Open Targets aggregate 0.30 · 1 independent evidence family

Obesity disorderLimited support
0.41
agreement 0.27–0.55
Genetic94%Literature6%

Open Targets aggregate 0.24 · 2 independent evidence families

Diabetes Mellitus, Type 1Limited support
0.36
agreement 0.22–0.50
Genetic98%Literature2%

Open Targets aggregate 0.22 · 2 independent evidence families

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
Alcohol drinking0.33
Aortic Diseases0.31
Restless Legs Syndrome0.30
Obesity disorder0.24
Diabetes Mellitus, Type 10.22
Musculoskeletal Diseases0.21
Tooth disorder0.19
Cardiomyopathy, Hypertrophic0.16

Tractability

Small molecules — Emerging

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

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
SM · Structure with LigandAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMM

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2025

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

Most cited

Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region.1,124 cites

Moffitt JR · Science (New York, N.Y.) · 2018

Neural Plasticity in Migraine Chronification.5 cites

Fila M · The European journal of neuroscience · 2025

Recent

Neural Plasticity in Migraine Chronification.

Fila M · The European journal of neuroscience · 2025

Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region.

Moffitt JR · Science (New York, N.Y.) · 2018

Europe PMC papers linked directly to this protein.