Pituitary adenylate cyclase-activating peptide

ADCYAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GEA, 2D2P, 2JOD
Identifiers
Aliases	ADCYAP1, PACAP, adenylate cyclase activating polypeptide 1
External IDs	OMIM: 102980; MGI: 105094; HomoloGene: 869; GeneCards: ADCYAP1; OMA:ADCYAP1 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18p11.32 Start 904,871 bp[1] End 912,172 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 E5 Start 93,506,445 bp[2] End 93,513,965 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in beta cell gonad Hypothalamus prefrontal cortex Brodmann area 9 gallbladder cingulate gyrus ganglionic eminence anterior cingulate cortex right frontal lobe Top expressed in lumbar spinal ganglion mammillary body ventromedial nucleus ventral tegmental area dorsomedial hypothalamic nucleus trigeminal ganglion habenula central gray substance of midbrain primary visual cortex superior frontal gyrus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function pituitary adenylate cyclase activating polypeptide activity hormone activity peptide hormone receptor binding protein binding pituitary adenylate cyclase-activating polypeptide receptor binding neuropeptide hormone activity signaling receptor binding Cellular component intracellular anatomical structure extracellular region terminal bouton extracellular space neuron projection perikaryon cell body fiber Biological process histamine secretion pituitary gland development regulation of G protein-coupled receptor signaling pathway negative regulation of glial cell proliferation female pregnancy cell-cell signaling negative regulation of cell cycle negative regulation of muscle cell apoptotic process behavioral fear response nervous system development activation of adenylate cyclase activity regulation of protein localization positive regulation of GTPase activity ATP metabolic process negative regulation of acute inflammatory response to non-antigenic stimulus regulation of oligodendrocyte progenitor proliferation cellular response to glucocorticoid stimulus positive regulation of gene expression negative regulation of GTPase activity positive regulation of synaptic transmission, glutamatergic positive regulation of chemokine (C-C motif) ligand 5 production regulation of postsynaptic membrane potential positive regulation of cell population proliferation negative regulation of potassium ion transport positive regulation of ERK1 and ERK2 cascade positive regulation of interleukin-6 production positive regulation of neuron projection development response to starvation ovarian follicle development sensory perception of pain response to ethanol negative regulation of acute inflammatory response to antigenic stimulus neuropeptide signaling pathway neuron projection development cAMP-mediated signaling positive regulation of somatostatin secretion positive regulation of transcription by RNA polymerase II positive regulation of protein kinase activity regulation of protein phosphorylation positive regulation of cytosolic calcium ion concentration insulin secretion positive regulation of growth hormone secretion regulation of signaling receptor activity G protein-coupled receptor signaling pathway adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of cAMP-mediated signaling brain development camera-type eye development positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 116 11516 Ensembl ENSG00000141433 ENSMUSG00000024256 UniProt P18509 O70176 RefSeq (mRNA) NM_001099733 NM_001117 NM_009625 NM_001315503 NM_001315504 RefSeq (protein) NP_001093203 NP_001108 NP_001302432 NP_001302433 NP_033755 Location (UCSC) Chr 18: 0.9 – 0.91 Mb Chr 17: 93.51 – 93.51 Mb PubMed search [3] [4]
Wikidata
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Pituitary adenylate cyclase-activating polypeptide, also known as PACAP, is a protein that in humans is encoded by the ADCYAP1 gene.^[5][6] PACAP is similar to vasoactive intestinal peptide. One of its effects is to stimulate enterochromaffin-like cells. It binds to vasoactive intestinal peptide receptor and to the pituitary adenylate cyclase-activating polypeptide receptor.

This gene encodes adenylate cyclase-activating polypeptide 1. Mediated by adenylate cyclase-activating polypeptide 1 receptors, this polypeptide stimulates adenylate cyclase and subsequently increases the cAMP level in target cells. Adenylate cyclase-activating polypeptide 1 not only is a hypophysiotropic hormone (i.e. a substance that induces activity in the hypophysis), but also functions as a neurotransmitter and neuromodulator. In addition, it plays a role in paracrine and autocrine regulation of certain types of cells. This gene has five exons. Exons 1 and 2 encode the 5' UTR and signal peptide, respectively; exon 4 encodes an adenylate cyclase-activating polypeptide 1-related peptide; and exon 5 encodes the mature peptide and 3' UTR. This gene encodes three different mature peptides, including two isotypes: a shorter form and a longer form.^[6]

A version of this gene has been associated with post-traumatic stress disorder (PTSD) in women (but not men).^[7] This disorder involves a maladaptive psychological response to traumatic, i.e. existence-threatening, events. Ressler et al. identified an association of a SNP in the gene coding for pituitary adenylate cyclase-activating polypeptide (PACAP), implicating this peptide and its receptor (PAC1) in PTSD. In mouse model of heavy alcohol drinking, PACAP seems to mediate alcohol effects on bed nucleus of the stria terminalis.^[8]

Both isoforms of pituitary adenylate cyclase-activating polypeptide (pituitary adenylate cyclase-activating polypeptide-38 and pituitary adenylate cyclase-activating polypeptide-27) have been implicated in migraine pathogenesis.^[9][10] A Danish research group led by Dr. Messoud Ashina found that intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 induced migraine attacks in 58% of people with migraine,^[9] whilst the corresponding migraine induction rate was 55% for pituitary adenylate cyclase-activating polypeptide-27.^[10] Treatments with monoclonal antibodies have been investigated to target pituitary adenylate cyclase-activating polypeptide or its receptors for the treatment of primary headache disorders. Alder BioPharmaceuticals's ALD1910, which targets the peptide, began a phase I study in October 2019.^[11][12] Amgen's AMG-301, which targets the PAC1 receptor, failed to show greater efficacy than placebo in phase II trials.^[13]

Pituitary adenylate cyclase-activating peptide has been shown to interact with secretin receptor.^[14]

• Adenylate cyclase
• Pituitary gland

• Pituitary+adenylate+cyclase-activating+polypeptide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.