Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNBHULA)

• DOT Name: Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1)
• Synonyms: PACAP type I receptor; PACAP-R-1; PACAP-R1
• Gene Name: ADCYAP1R1
• UniProt ID: PACR_HUMAN
• PDB ID: 2JOD; 3N94; 6LPB; 6M1H; 6M1I; 6P9Y; 7JQD; 8E3X
• Pfam ID: PF00002 ; PF02793
• Sequence:
  MAGVVHVSLAALLLLPMAPAMHSDCIFKKEQAMCLEKIQRANELMGFNDSSPGCPGMWDN
  ITCWKPAHVGEMVLVSCPELFRIFNPDQVWETETIGESDFGDSNSLDLSDMGVVSRNCTE
  DGWSEPFPHYFDACGFDEYESETGDQDYYYLSVKALYTVGYSTSLVTLTTAMVILCRFRK
  LHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAVMVFFHYCVVSN
  YFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMN
  DSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIP
  LFGIHYTVFAFSPENVSKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWRSWKV
  NRYFAVDFKHRHPSLASSGVNGGTQLSILSKSSSQIRMSGLPADNLAT
• Function: This is a receptor for PACAP-27 and PACAP-38. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. May regulate the release of adrenocorticotropin, luteinizing hormone, growth hormone, prolactin, epinephrine, and catecholamine. May play a role in spermatogenesis and sperm motility. Causes smooth muscle relaxation and secretion in the gastrointestinal tract.
• Tissue Specificity: Most abundant in the brain, low expression in the lung, liver, thymus, spleen, pancreas and placenta.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Circadian entrainment (hsa04713)
  Insulin secretion (hsa04911)
  Renin secretion (hsa04924)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Glucagon-type ligand receptors (R-HSA-420092)
  NGF-independant TRKA activation (R-HSA-187024)

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[7]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[2]
Marinol	DM70IK5	Approved	Marinol increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[2]
Haloperidol	DM96SE0	Approved	Haloperidol affects the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[4]
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[4]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [4] Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors. Neurochem Res. 2017 Apr;42(4):943-952. doi: 10.1007/s11064-016-2127-2. Epub 2016 Nov 30.
• [5] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [6] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.