ADCYAP1R1

ADCYAP1R1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JOD
Identifiers
Aliases	ADCYAP1R1 , PAC1, PAC1R, PACAPR, PACAPRI, ADCYAP receptor type I
External IDs	OMIM: 102981; MGI: 108449; HomoloGene: 870; GeneCards: ADCYAP1R1; OMA:ADCYAP1R1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p14.3 Start 31,052,308 bp [1] End 31,111,479 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6|6 B3 Start 55,428,963 bp [2] End 55,478,436 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence nucleus accumbens caudate nucleus amygdala entorhinal cortex right frontal lobe internal globus pallidus cingulate gyrus anterior cingulate cortex right hemisphere of cerebellum Top expressed in paraventricular nucleus of hypothalamus dentate gyrus of hippocampal formation granule cell arcuate nucleus lateral septal nucleus Rostral migratory stream dorsomedial hypothalamic nucleus ventral tegmental area substantia nigra lateral hypothalamus ventromedial nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity adenylate cyclase binding neuropeptide binding vasoactive intestinal polypeptide receptor activity signal transducer activity protein binding transmembrane signaling receptor activity signaling receptor activity G protein-coupled peptide receptor activity peptide hormone binding Cellular component cytoplasm integral component of membrane endosome rough endoplasmic reticulum membrane bicellular tight junction receptor complex plasma membrane integral component of plasma membrane cell surface caveola neuron projection intracellular membrane-bounded organelle Biological process cell differentiation multicellular organismal response to stress response to estradiol positive regulation of calcium ion transport into cytosol positive regulation of inositol phosphate biosynthetic process negative regulation of cell death activation of phospholipase C activity multicellular organism development cell surface receptor signaling pathway development of primary female sexual characteristics spermatogenesis response to ethanol cAMP-mediated signaling signal transduction positive regulation of small GTPase mediated signal transduction G protein-coupled receptor signaling pathway positive regulation of cAMP-mediated signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 117 11517 Ensembl ENSG00000078549 ENSMUSG00000029778 UniProt P41586 P70205 RefSeq (mRNA) NM_001118 NM_001199635 NM_001199636 NM_001199637 NM_001025372 NM_007407 RefSeq (protein) NP_001109 NP_001186564 NP_001186565 NP_001186566 NP_001020543 NP_031433 Location (UCSC) Chr 7: 31.05 – 31.11 Mb Chr 6: 55.43 – 55.48 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC₁, is a protein that in humans is encoded by the ADCYAP1R1 gene. ^[5] This receptor binds pituitary adenylate cyclase activating peptide. ^{[6] [7]}

Function

PAC₁ is a membrane-associated protein and shares significant homology with members of the G-protein coupled class B glucagon/secretin receptor family. ^[8] This receptor mediates diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. Alternative splicing of two exons of this gene generates four major splice variants, but their full-length nature has not been determined. ^[5] PAC₁ is expressed in the adrenal medulla, pancreatic acini, uterus, myenteric plexus and brain. ^{[9] [10] [11]} It is also expressed in the trigeminal, otic and superior cervical ganglia (prejunctional) and cerebral arteries (postjunctional). ^[12]

Ligands

Agonists

• PACAP-38 (endogenous peptide agonist, full length version) - also activates other receptors VIP, GPR55 and MRGPRX2 and the Secretin receptor. ^[13]
• PACAP-27 (endogenous peptide agonist, shorter fragment which retains activity)

Antagonists

• PACAP(6-38) - N-terminal truncated version of the endogenous peptide agonist which acts as a potent PAC1 antagonist ^[14]
• BAY 2686013 ^[15]
• PA-915 ^{[16] [17]}

References

1. GRCh38: Ensembl release 89: ENSG00000078549 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029778 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: ADCYAP1R1 adenylate cyclase activating polypeptide 1 (pituitary) receptor type I".
6. Ogi K, Miyamoto Y, Masuda Y, Habata Y, Hosoya M, Ohtaki T, Masuo Y, Onda H, Fujino M (Nov 1993). "Molecular cloning and functional expression of a cDNA encoding a human pituitary adenylate cyclase activating polypeptide receptor". Biochemical and Biophysical Research Communications. 196 (3): 1511–21. doi:10.1006/bbrc.1993.2423. PMID   7902709.
7. Vaudry D, Gonzalez BJ, Basille M, Yon L, Fournier A, Vaudry H (Jun 2000). "Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions". Pharmacological Reviews. 52 (2): 269–324. PMID   10835102. Archived from the original on 2008-07-05. Retrieved 2007-11-25.
8. Wang J, Song X, Zhang D, Chen X, Li X, Sun Y, Li C, Song Y, Ding Y, Ren R, Harrington EH, Hu LA, Zhong W, Xu C, Huang X, Wang HW, Ma Y (2020). "Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism". Cell Res. 30 (5): 436–445. doi: 10.1038/s41422-020-0280-2 . PMC   7196072 . PMID   32047270.
9. Reubi JC (2000). "In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications". Annals of the New York Academy of Sciences. 921 (1): 1–25. Bibcode:2000NYASA.921....1R. doi:10.1111/j.1749-6632.2000.tb06946.x. PMID   11193811. S2CID   21204750.
10. Reubi JC, Läderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA (Jun 2000). "Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin". Cancer Research. 60 (11): 3105–12. PMID   10850463.
11. Yon L, Breault L, Contesse V, Bellancourt G, Delarue C, Fournier A, Lehoux JG, Vaudry H, Gallo-Payet N (Apr 1998). "Localization, characterization, and second messenger coupling of pituitary adenylate cyclase-activating polypeptide receptors in the fetal human adrenal gland during the second trimester of gestation" (PDF). The Journal of Clinical Endocrinology and Metabolism. 83 (4): 1299–305. doi:10.1210/jcem.83.4.4690. PMID   9543159.
12. Knutsson M, Edvinsson L (Mar 2002). "Distribution of mRNA for VIP and PACAP receptors in human cerebral arteries and cranial ganglia". NeuroReport. 13 (4): 507–9. doi:10.1097/00001756-200203250-00030. PMID   11930171. S2CID   30329669.
13. Tasma Z, Hay DL (August 2025). "Decoding PACAP signaling: Splice variants, pathways and designer drugs". Cephalalgia. 45 (8) 03331024251363560. doi:10.1177/03331024251363560. PMID   40767099.
14. Robberecht P, Gourlet P, De Neef P, Woussen-Colle MC, Vandermeers-Piret MC, Vandermeers A, Christophe J (July 1992). "Structural requirements for the occupancy of pituitary adenylate-cyclase-activating-peptide (PACAP) receptors and adenylate cyclase activation in human neuroblastoma NB-OK-1 cell membranes. Discovery of PACAP(6-38) as a potent antagonist". European Journal of Biochemistry. 207 (1): 239–246. doi:10.1111/j.1432-1033.1992.tb17043.x. PMID   1321043.
15. Langer G, Scott J, Lind C, Otto C, Bothe U, Laux-Biehlmann A, Müller J, le Roy B, Irlbacher H, Nowak-Reppel K, Schlüter A, Davenport AJ, Slack M, Bäurle S (September 2023). "Discovery and In Vitro Characterization of BAY 2686013, an Allosteric Small Molecule Antagonist of the Human Pituitary Adenylate Cyclase-Activating Polypeptide Receptor". Molecular Pharmacology. 104 (3): 105–114. doi:10.1124/molpharm.122.000662. PMID   37348913.
16. Takasaki I, Ogashi H, Okada T, Shimodaira A, Hayakawa D, Watanabe A, Miyata A, Kurihara T, Gouda H, Toyooka N (January 2020). "Synthesis of a novel and potent small-molecule antagonist of PAC1 receptor for the treatment of neuropathic pain". European Journal of Medicinal Chemistry. 186 111902. doi:10.1016/j.ejmech.2019.111902. PMID   31771828.
17. Shintani Y, Hayata-Takano A, Takasaki I, Kurihara T, Miyata A, Yamano Y, Ikuta M, Takeshita R, Murata K, Oguri T, Asaka C, Nunomura K, Lin B, Nakagawa S, Okada T, Toyooka N, Takumi T, Ago Y, Takuma K, Hashimoto H (September 2025). "Rapid and long-lasting antidepressant-like effects of the pituitary adenylate cyclase-activating polypeptide receptor antagonist PA-915 in chronic stress mouse models". Molecular Psychiatry. doi:10.1038/s41380-025-03209-4. PMID   40908362.

Further reading

• Stoffel M, Espinosa R, Trabb JB, Le Beau MM, Bell GI (Oct 1994). "Human type I pituitary adenylate cyclase activating polypeptide receptor (ADCYAP1R): localization to chromosome band 7p14 and integration into the cytogenetic, physical, and genetic map of chromosome 7". Genomics. 23 (3): 697–9. doi:10.1006/geno.1994.1560. PMID   7851900.
• Ogi K, Miyamoto Y, Masuda Y, Habata Y, Hosoya M, Ohtaki T, Masuo Y, Onda H, Fujino M (Nov 1993). "Molecular cloning and functional expression of a cDNA encoding a human pituitary adenylate cyclase activating polypeptide receptor". Biochemical and Biophysical Research Communications. 196 (3): 1511–21. doi:10.1006/bbrc.1993.2423. PMID   7902709.
• Ohtaki T, Masuda Y, Ishibashi Y, Kitada C, Arimura A, Fujino M (Dec 1993). "Purification and characterization of the receptor for pituitary adenylate cyclase-activating polypeptide". The Journal of Biological Chemistry. 268 (35): 26650–7. doi: 10.1016/S0021-9258(19)74361-0 . PMID   8253796.
• Pisegna JR, Wank SA (Jul 1996). "Cloning and characterization of the signal transduction of four splice variants of the human pituitary adenylate cyclase activating polypeptide receptor. Evidence for dual coupling to adenylate cyclase and phospholipase C". The Journal of Biological Chemistry. 271 (29): 17267–74. doi: 10.1074/jbc.271.29.17267 . PMC   6721843 . PMID   8663363.
• Pantaloni C, Brabet P, Bilanges B, Dumuis A, Houssami S, Spengler D, Bockaert J, Journot L (Sep 1996). "Alternative splicing in the N-terminal extracellular domain of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor modulates receptor selectivity and relative potencies of PACAP-27 and PACAP-38 in phospholipase C activation". The Journal of Biological Chemistry. 271 (36): 22146–51. doi: 10.1074/jbc.271.36.22146 . PMID   8703026.
• Solano RM, Carmena MJ, Carrero I, Cavallaro S, Roman F, Hueso C, Travali S, Lopez-Fraile N, Guijarro LG, Prieto JC (Jul 1996). "Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate". Endocrinology. 137 (7): 2815–22. doi: 10.1210/en.137.7.2815 . PMID   8770902.
• Wei Y, Mojsov S (Nov 1996). "Tissue specific expression of different human receptor types for pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide: implications for their role in human physiology". Journal of Neuroendocrinology. 8 (11): 811–7. doi:10.1046/j.1365-2826.1996.05191.x. PMID   8933357. S2CID   22302790.
• Brabet P, Diriong S, Journot L, Bockaert J, Taviaux S (Nov 1996). "Localization of the human pituitary adenylate cyclase-activating polypeptide receptor (PACAP1-R) gene to 7p15-p14 by fluorescence in situ hybridization". Genomics. 38 (1): 100–2. doi:10.1006/geno.1996.0600. PMID   8954788.
• Yon L, Breault L, Contesse V, Bellancourt G, Delarue C, Fournier A, Lehoux JG, Vaudry H, Gallo-Payet N (Apr 1998). "Localization, characterization, and second messenger coupling of pituitary adenylate cyclase-activating polypeptide receptors in the fetal human adrenal gland during the second trimester of gestation" (PDF). The Journal of Clinical Endocrinology and Metabolism. 83 (4): 1299–305. doi:10.1210/jcem.83.4.4690. PMID   9543159.
• Steinhoff M, McGregor GP, Radleff-Schlimme A, Steinhoff A, Jarry H, Schmidt WE (Mar 1999). "Identification of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type 1 receptor in human skin: expression of PACAP-38 is increased in patients with psoriasis". Regulatory Peptides. 80 (1–2): 49–55. doi:10.1016/S0167-0115(99)00010-5. PMID   10235634. S2CID   8591698.
• Zeng N, Athmann C, Kang T, Lyu RM, Walsh JH, Ohning GV, Sachs G, Pisegna JR (Nov 1999). "PACAP type I receptor activation regulates ECL cells and gastric acid secretion". The Journal of Clinical Investigation. 104 (10): 1383–91. doi:10.1172/JCI7537. PMC   409843 . PMID   10562300.
• Dautzenberg FM, Mevenkamp G, Wille S, Hauger RL (Dec 1999). "N-terminal splice variants of the type I PACAP receptor: isolation, characterization and ligand binding/selectivity determinants". Journal of Neuroendocrinology. 11 (12): 941–9. doi:10.1046/j.1365-2826.1999.00411.x. PMID   10583729. S2CID   35761617.
• Scaldaferri ML, Modesti A, Palumbo C, Ulisse S, Fabbri A, Piccione E, Frajese G, Moretti C (Mar 2000). "Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta". Endocrinology. 141 (3): 1158–67. doi: 10.1210/endo.141.3.7346 . PMID   10698193.
• Busto R, Prieto JC, Bodega G, Zapatero J, Carrero I (Feb 2000). "Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung". Peptides. 21 (2): 265–9. doi:10.1016/S0196-9781(99)00202-8. PMID   10764955. S2CID   44951090.
• Knutsson M, Edvinsson L (Mar 2002). "Distribution of mRNA for VIP and PACAP receptors in human cerebral arteries and cranial ganglia". NeuroReport. 13 (4): 507–9. doi:10.1097/00001756-200203250-00030. PMID   11930171. S2CID   30329669.
• Miampamba M, Germano PM, Arli S, Wong HH, Scott D, Taché Y, Pisegna JR (May 2002). "Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons". Regulatory Peptides. 105 (3): 145–54. doi:10.1016/S0167-0115(02)00003-4. PMC   6736535 . PMID   11959368.
• Le SV, Yamaguchi DJ, McArdle CA, Tachiki K, Pisegna JR, Germano P (Nov 2002). "PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumor cells". Regulatory Peptides. 109 (1–3): 115–25. doi:10.1016/S0167-0115(02)00194-5. PMC   6736540 . PMID   12409223.
• Ronaldson E, Robertson DN, Johnson MS, Holland PJ, Mitchell R, Lutz EM (Nov 2002). "Specific interaction between the hop1 intracellular loop 3 domain of the human PAC(1) receptor and ARF". Regulatory Peptides. 109 (1–3): 193–8. doi:10.1016/S0167-0115(02)00204-5. PMID   12409233. S2CID   25745650.
• Isobe K, Tatsuno I, Yashiro T, Nanmoku T, Takekoshi K, Kawakami Y, Nakai T (Feb 2003). "Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis". Regulatory Peptides. 110 (3): 213–7. doi:10.1016/S0167-0115(02)00209-4. PMID   12573802. S2CID   21201447.

External links

• "VIP and PACAP Receptors: PAC₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• Human ADCYAP1R1 genome location and ADCYAP1R1 gene details page in the UCSC Genome Browser .

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