Pituitary_adenylate_cyclase-activating_peptide Knowpia

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
Gene location (Human)
Chr.	Chromosome 18 (human)
End	912,172 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	93,513,965 bp
RNA expression pattern
	Top expressed in
	hypothalamus; ; prefrontal cortex; ; Brodmann area 9; ; gallbladder; ; cingulate gyrus; ; ganglionic eminence; ; Brodmann area 10; ; appendix; ; right coronary artery; ; right lung;
	Top expressed in
	mammillary body; ; ventromedial nucleus; ; ventral tegmental area; ; dorsomedial hypothalamic nucleus; ; trigeminal ganglion; ; habenula; ; superior frontal gyrus; ; cingulate gyrus; ; barrel cortex; ; inferior colliculus;
	More reference expression data
	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
	116
	11516
	ENSG00000141433
	ENSMUSG00000024256
	P18509
	O70176
	NM_001099733; NM_001117
	NM_009625; NM_001315503; NM_001315504
	NP_001093203; NP_001108
	NP_001302432; NP_001302433; NP_033755
	Wikidata
View/Edit Human	View/Edit Mouse

Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene.^[5]^[6] pituitary adenylate cyclase-activating polypeptide 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.

Function edit

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]

Headache Disorders edit

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]

Interactions edit

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

References edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000141433 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024256 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Hosoya M, Kimura C, Ogi K, Ohkubo S, Miyamoto Y, Kugoh H, et al. (January 1992). "Structure of the human pituitary adenylate cyclase activating polypeptide (PACAP) gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1129 (2): 199–206. doi:10.1016/0167-4781(92)90488-l. PMID 1730060.
^ ^a ^b "Entrez Gene: ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary)".
^ Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, et al. (February 2011). "Post-traumatic stress disorder is associated with pituitary adenylate cyclase-activating polypeptide and the PAC1 receptor". Nature. 470 (7335): 492–7. Bibcode:2011Natur.470..492R. doi:10.1038/nature09856. PMC 3046811. PMID 21350482.
^ Lauren Lepeak ... (1 December 2023). "Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice". eNeuro. 10 (12). doi:10.1523/ENEURO.0424-23.2023. PMC 10755645. PMID 38053471.
^ ^a ^b Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M (January 2009). "pituitary adenylate cyclase-activating polypeptide-38 induces migraine-like attacks in patients with migraine without aura". Brain. 132 (Pt 1): 16–25. doi:10.1093/brain/awn307. PMID 19052139.
^ ^a ^b Ghanizada H, Al-Karagholi MA, Arngrim N, Olesen J, Ashina M (January 2020). "PACAP27 induces migraine-like attacks in migraine patients". Cephalalgia. 40 (1): 57–67. doi:10.1177/0333102419864507. PMID 31299857. S2CID 196349669.
^ Bertels Z, Pradhan AA (July 2019). "Emerging Treatment Targets for Migraine and Other Headaches". Headache. 59 Suppl 2 (S2): 50–65. doi:10.1111/head.13585. PMC 6986366. PMID 31291018.
^ "Alder BioPharmaceuticals® Announces First-in-Human Dosing in Phase 1 ALD1910 Study for Preventive Treatment of Migraine". Globenewswire News Room. GlobeNewswire. 10 October 2019. Retrieved 10 October 2019.
^ Ashina M, Doležil D, Bonner JH, Zhou L, Klatt J, Picard H, Mikol DD (January 2021). "A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention". Cephalalgia. 41 (1): 33–44. doi:10.1177/0333102420970889. PMC 7786389. PMID 33231489.
^ Felley CP, Qian JM, Mantey S, Pradhan T, Jensen RT (December 1992). "Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release". The American Journal of Physiology. 263 (6 Pt 1): G901-7. doi:10.1152/ajpgi.1992.263.6.G901. PMID 1335692.