Nomenclature: PAC1 receptor

Family: VIP and PACAP receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 468 7p14 ADCYAP1R1 adenylate cyclase activating polypeptide 1 (pituitary) receptor type I 36,55
Mouse 7 496 6B3 Adcyap1r1 adenylate cyclase activating polypeptide 1 receptor 1 1,21
Rat 7 495 4q24 Adcyap1r1 adenylate cyclase activating polypeptide 1 receptor 1 5,45
Previous and Unofficial Names
PAC1R
PACAP type 1 receptor
PACAP
PVR1
PACAP type I
PAC1
PACAPR
PACAP receptor 1
PAC1-R
PACAP-R1A
PACAPR1
PACAPR1A
PACAP type IA receptor
PACAP-R-1
PACAP-R-1A
adenylate cyclase activating polypeptide 1 (pituitary) receptor type I
adenylate cyclase activating polypeptide 1 type 1 receptor
pituitary adenylate cyclase activating polypeptide 1 receptor (1)
pituitary adenylate cyclase activating polypeptide receptor
pituitary adenylate cyclase-activating polypeptide type IA receptor
rat pituitary adenylate cyclase activating polypeptide 1 receptor (1)
PACAP1-R
2900024I10Rik
AI846590
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of PAC1 receptor extracellular domain
PDB Id:  3N94
Resolution:  1.9Å
Species:  Human
References:  27
Natural/Endogenous Ligands
PACAP-27 {Sp: Human, Mouse, Rat, Sheep}
PACAP-38 {Sp: Human, Mouse, Rat}
PHI {Sp: Mouse, Rat}
PHM {Sp: Human}
PHV {Sp: Rat} , PHV {Sp: Human}
VIP {Sp: Human, Mouse, Rat}
Comments: PACAP-27 and PACAP-38 are the principal endogenous agonists
Rank order of potency (Human)
PACAP-27 (ADCYAP1, P18509), PACAP-38 (ADCYAP1, P18509) >> VIP (VIP, P01282)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]PACAP-27 Hs Agonist 9.1 pKd 44
pKd 9.1 (Kd 8.7x10-10 M) [44]
Description: Binding to NIH/3T3 cells stably expressing recombinant receptor
PACAP-27 {Sp: Human, Mouse, Rat, Sheep} Rn Agonist 8.5 – 8.8 pKi 6
pKi 8.8 (Ki 1.5x10-9 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pKi 8.5 (Ki 3x10-9 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
PACAP-38 {Sp: Human, Mouse, Rat} Rn Agonist 8.4 – 8.8 pKi 6
pKi 8.8 (Ki 1.5x10-9 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pKi 8.4 (Ki 4x10-9 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
[Ac-His1]PACAP-27 Rn Agonist 8.0 – 8.3 pKi 6
pKi 8.3 (Ki 5x10-9 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pKi 8.0 (Ki 1x10-8 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
PACAP-38 {Sp: Human, Mouse, Rat} Hs Agonist 6.9 – 9.0 pKi 9
pKi 9.0 (Ki 1.1x10-9 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the full length receptor (ENST00000304166)
pKi 8.8 (Ki 1.7x10-9 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the PAC1 short receptor (ENST00000409363)
pKi 6.9 (Ki 1.21x10-7 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the PAC1 very short receptor
PACAP-27 {Sp: Human, Mouse, Rat, Sheep} Hs Agonist 6.9 – 8.5 pKi 9
pKi 8.5 (Ki 2.9x10-9 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the full length receptor (ENST00000304166)
pKi 8.5 (Ki 3.1x10-9 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the PAC1 short receptor (ENST00000409363)
pKi 6.9 (Ki 1.29x10-7 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the PAC1 very short receptor
VIP {Sp: Human, Mouse, Rat} Hs Agonist 6.0 – 8.4 pKi 9
pKi 8.4 (Ki 4.4x10-9 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the PAC1 short receptor (ENST00000409363)
pKi 6.3 (Ki 4.58x10-7 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the full length receptor (ENST00000304166)
pKi <6.0 (Ki >1x10-6 M) [9]
Description: inhibition of [125I]-PACAP-27 binding to membranes from HEK293 cells stably expressing the PAC1 very short receptor
VIP {Sp: Human, Mouse, Rat} Rn Agonist 5.5 – 5.8 pKi 6
pKi 5.8 (Ki 1.5x10-6 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pKi 5.5 (Ki 3.5x10-6 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
PACAP-27 {Sp: Human, Mouse, Rat, Sheep} Rn Agonist 10.0 – 10.1 pEC50 6
pEC50 10.1 (EC50 8x10-11 M) [6]
Description: stimulation of adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
pEC50 10.0 (EC50 1x10-10 M) [6]
Description: stimulation of adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
PACAP-38 {Sp: Human, Mouse, Rat} Rn Agonist 9.5 – 10.0 pEC50 6,35
pEC50 10.0 (EC50 1x10-10 M) [6]
Description: stimulation of adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
pEC50 10.0 (EC50 1x10-10 M) [6]
Description: stimulation of adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pEC50 9.5 (EC50 3.4x10-10 M) [35]
Description: stimulation of adenylate cyclase in COS cells transiently expressing recombinant receptor
PACAP-27 {Sp: Human, Mouse, Rat, Sheep} Hs Agonist 7.4 – 10.6 pEC50 9,11,34
pEC50 10.6 (EC50 2.6x10-11 M) [11]
Description: cyclic AMP formation in CHO cells stably expressing recombinant receptor
pEC50 9.1 (EC50 8x10-10 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the full length receptor (ENST00000304166)
pEC50 9.0 (EC50 1x10-9 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the PAC1 short receptor (ENST00000409363)
pEC50 8.7 (EC50 2x10-9 M) [34]
Description: stimulation of cyclic AMP formation in NIH/3T3 cells stably expressing the recombinant receptor
pEC50 8.5 (EC50 3.3x10-9 M) [11]
Description: calcium influx in CHO cells stably expressing recombinant receptor
pEC50 7.4 (EC50 3.7x10-8 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the PAC1 very short receptor
PACAP-38 {Sp: Human, Mouse, Rat} Hs Agonist 7.5 – 10.3 pEC50 9,11
pEC50 10.3 (EC50 4.9x10-11 M) [11]
Description: cyclic AMP formation in CHO cells stably expressing recombinant receptor
pEC50 9.2 (EC50 6x10-10 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the full length receptor (ENST00000304166)
pEC50 9.2 (EC50 7x10-10 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the PAC1 short receptor (ENST00000409363)
pEC50 8.3 (EC50 5.1x10-9 M) [11]
Description: calcium influx in CHO cells stably expressing recombinant receptor
pEC50 7.5 (EC50 2.9x10-8 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the PAC1 very short receptor
maxadilan Hs Agonist 6.2 – 10.3 pEC50 11
pEC50 10.3 (EC50 5.4x10-11 M) [11]
Description: cyclic AMP formation in CHO cells stably expressing recombinant receptor
pEC50 6.2 (EC50 5.68x10-7 M) [11]
Description: calcium influx in CHO cells stably expressing recombinant receptor
VIP {Sp: Human, Mouse, Rat} Hs Agonist 6.0 – 8.7 pEC50 9,11,34
pEC50 8.7 (EC50 2.1x10-9 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the PAC1 short receptor (ENST00000409363)
pEC50 7.8 (EC50 1.51x10-8 M) [11]
Description: cyclic AMP formation in CHO cells stably expressing recombinant receptor
pEC50 6.7 (EC50 1.86x10-7 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the full length receptor (ENST00000304166)
pEC50 6.4 (EC50 3.89x10-7 M) [11]
Description: calcium influx in CHO cells stably expressing recombinant receptor
pEC50 6.4 (EC50 3.73x10-7 M) [9]
Description: stimulation of cyclic AMP formation in HEK293 cells stably expressing the PAC1 very short receptor
pEC50 <6.0 (EC50 >1x10-6 M) [34]
Description: stimulation of cyclic AMP formation in NIH/3T3 cells stably expressing the recombinant receptor
PG 99-465 Hs Agonist 7.1 pEC50 11
pEC50 7.1 (EC50 7.13x10-8 M) [11]
Description: cyclic AMP formation in CHO cells stably expressing recombinant receptor
VIP {Sp: Human, Mouse, Rat} Rn Agonist 7.1 pEC50 6
pEC50 7.1 (EC50 8x10-8 M) [6]
Description: stimulation of adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
pEC50 7.1 (EC50 8x10-8 M) [6]
Description: stimulation of adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
[Lys15,Arg16,Leu27]VIP-(1–7)/GRF-(8–27)-NH2 Hs Agonist <6.0 pEC50 34
pEC50 <6.0 (EC50 >1x10-6 M) [34]
Description: stimulation of cyclic AMP formation in NIH/3T3 cells stably expressing the recombinant receptor
Ro 25-1553 Hs Agonist <6.0 pEC50 34
pEC50 <6.0 (EC50 >1x10-6 M) [34]
Description: stimulation of cyclic AMP formation in NIH/3T3 cells stably expressing the recombinant receptor
[Ala11,22,28]VIP Hs Agonist 5.0 – 5.8 pEC50 11
pEC50 5.8 (EC50 1.582x10-6 M) [11]
Description: cyclic AMP formation in CHO cells stably expressing recombinant receptor
pEC50 <5.0 (EC50 >1x10-5 M) [11]
Description: calcium influx in CHO cells stably expressing recombinant receptor
PACAP-27 {Sp: Human, Mouse, Rat, Sheep} Hs Agonist 7.6 pIC50 34
pIC50 7.6 (IC50 2.5x10-8 M) [34]
Description: inhibition of [125I]-PACAP-27 binding to membranes from NIH/3T3 cells stably expressing the recombinant receptor
[Lys15,Arg16,Leu27]VIP-(1–7)/GRF-(8–27)-NH2 Hs Agonist <6.0 pIC50 34
pIC50 <6.0 (IC50 >1x10-6 M) [34]
Description: inhibition of [125I]-PACAP-27 binding to membranes from NIH/3T3 cells stably expressing the recombinant receptor
Ro 25-1553 Hs Agonist <6.0 pIC50 34
pIC50 <6.0 (IC50 >1x10-6 M) [34]
Description: inhibition of [125I]-PACAP-27 binding to membranes from NIH/3T3 cells stably expressing the recombinant receptor
VIP {Sp: Human, Mouse, Rat} Hs Agonist <6.0 pIC50 34
pIC50 <6.0 (IC50 >1x10-6 M) [34]
Description: inhibition of [125I]-PACAP-27 binding to membranes from NIH/3T3 cells stably expressing the recombinant receptor
VIP {Sp: Human, Mouse, Rat} Rn Agonist 5.7 pIC50 16
pIC50 5.7 (IC50 2x10-6 M) [16]
Description: Inhibition of [125I]-Ac-His1-PACAP-27 binding in membranes from CHO cells expressing recombinant receptor
BAY 55-9837 Hs Agonist <5.0 pIC50 56
pIC50 <5.0 (IC50 >1x10-5 M) [56]
Description: inhibition of [125I]-PACAP-27 binding to membranes from CHO cells stably expressing the recombinant receptor
Ro 25-1553 Rn Agonist <5.0 pIC50 17
pIC50 <5.0 (IC50 >1x10-5 M) [17]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the recombinant receptor
[Arg16]chicken secretin Rn Agonist 4.7 pIC50 16
pIC50 4.7 (IC50 2x10-5 M) [16]
Description: Inhibition of [125I]-Ac-His1-PACAP-27 binding in membranes from CHO cells expressing recombinant receptor
secretin {Sp: Pig} Rn Agonist 4.5 pIC50 16
pIC50 4.5 (IC50 3x10-5 M) [16]
Description: Inhibition of [125I]-Ac-His1-PACAP-27 binding in membranes from CHO cells expressing recombinant receptor
[Lys15,Arg16,Leu27]VIP-(1–7)/GRF-(8–27)-NH2 Hs Full agonist - -
[125I]VIP Hs Full agonist - -
[Arg16]chicken secretin Hs Full agonist - -
View species-specific agonist tables
Agonist Comments
Maxadilan is a selective agonist of PAC1 receptors but its use has been limited due to problems with availability.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PACAP-(6-38) Rn Antagonist 7.5 – 8.1 pKi 6
pKi 8.1 (Ki 8x10-9 M) [6]
Description: inhibition of PACAP-27 stimulated adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pKi 8.0 (Ki 1x10-8 M) [6]
Description: inhibition of PACAP-27 stimulated adenylate cyclase in CHO cells stably expressing the rat PAC1 receptor isoform lacking the hip and hop exons
pKi 7.5 (Ki 3x10-8 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
pKi 7.5 (Ki 3x10-8 M) [6]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the rat PAC1 receptor isoform including the hop1 exon
N-stearyl-[Nle17] neurotensin-(6-11)/VIP-(7-28) Hs Antagonist 7.2 pIC50 34
pIC50 7.2 (IC50 6.5x10-8 M) [34]
Description: inhibition of [125I]-PACAP-27 binding to membranes from NIH/3T3 cells stably expressing the recombinant receptor
M65 Hs Antagonist 6.6 – 6.8 pIC50 11
pIC50 6.8 (IC50 1.496x10-7 M) [11]
Description: inhibition of cyclic AMP formation stimulated by 0.1nM PACAP-27 in CHO cells stably expressing recombinant receptor
pIC50 6.6 (IC50 2.774x10-7 M) [11]
Description: inhibition of calcium influx stimulated by 30nM PACAP-27 in CHO cells stably expressing recombinant receptor
PG 97-269 Rn Antagonist 4.5 pIC50 15
pIC50 4.5 (IC50 3x10-5 M) [15]
Description: inhibition of [125I]-[Ac-His1]PACAP-27 binding to membranes from CHO cells stably expressing the recombinant receptor
PG 97-269 Hs Antagonist - - 16
[16]
View species-specific antagonist tables
Antagonist Comments
Deletion mutants of maxadilan (M65 and Max.d.4) have been reported to be selective PAC1 receptor antagonists but have not been extensively used due to problems of availability. PACAP(6-38) has been used as a PAC1 receptor antagonist in many studies, but does not discriminate between PAC1 and VPAC2 receptors [28]. Small molecule antagonists of PAC1 receptors have been described, but have not yet been extensively characterised [3].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  10
Secondary Transduction Mechanisms
Transducer Effector/Response
G protein (identity unknown) Phospholipase C stimulation
References:  10
Tissue Distribution
Adrenal medulla; pancreatic acini; glands of uterus; myenteric plexus; CNS
Species:  Human
Technique:  Receptor autoradiography
References:  49-50,61
Embryonic nervous system (including roof and floor plates of the neural tube, rhombencephalon, dorsal root and trigeminal ganglia and the sympathetic chain)
Species:  Mouse
Technique:  in situ hybridisation.
References:  51,60,62
Hypothalamus, brain stem, pituitary, adrenal gland, testis
Species:  Rat
Technique:  in situ hybridisation and northern blot
References:  54
Testis, epididymis, adrenal chromaffin cells
Species:  Rat
Technique:  receptor autoradiography and ligand binding
References:  53
Dorsal horn of spinal cord
Species:  Rat
Technique:  Receptor autoradiography
References:  23
Embryonic nervous system
Species:  Rat
Technique:  in situ hybridisation.
References:  2
Widespread in the CNS, especially in glomerular and internal granular layers of olfactory bulb, cerebral cortex, dentate gyrus, supraoptic nuclei, brainstem, cerebellum (purkinje cells and granular layer); anterior pituitary gland
Species:  Rat
Technique:  Immunocytochemistry and in situ hybridisation
References:  20,52
Thyroid and parathyroid glands.
Species:  Rat
Technique:  in situ hybridisation
References:  12
Adrenal medulla
Species:  Rat
Technique:  Receptor autoradiography and in situ hybridisation
References:  33
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
CHO cells stably transfected with PAC1 receptor cDNA.
Species:  Rat
Tissue:  CHO cells.
Response measured:  cAMP formation.
References:  6,10
CHO cells stably transfected with PAC1 receptor cDNA.
Species:  Rat
Tissue:  CHO cells.
Response measured:  IP3 production, intracellular Ca++ (Fura-2 AM).
References:  10
Pigment dispersion in Xenopus melanophores transfected with PAC1 receptor cDNA.
Species:  Rat
Tissue:  Xenopus melanophores.
Response measured:  Pigment dispersion.
References:  41
Physiological Functions
Modulates glutamate-induced phase shifts in circadian rhythm of neuronal firing and clock gene expression in the suprachiasmatic nucleus, leading to changes in the magnitude of light-induced phase shifts in circadian behaviour in whole animals.
Species:  Mouse
Tissue:  suprachiasmatic nucleus
References:  4,7,19,32
Influences proliferation, apoptosis and migration of immature cerebellar granule cells
Species:  Rat
Tissue:  cerebellum
References:  13-14,57-59
Stimulation of catecholamine secretion from the adrenal medulla
Species:  Rat
Tissue:  adrenal medulla
References:  47
Physiological Consequences of Altering Gene Expression
PAC1 receptor–deficient mice display impaired insulinotropic response to glucose, reduced glucose tolerance and impaired glucagon response to insulin-induced hypoglycaemia
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  22,42
PAC1 receptor–deficient mice display impairments in long-term potentiation and associative learning. Mice with a ubiquitous but not with a forebrain-specific deletion of the PAC1 receptor exhibited elevated locomotor activity and strongly reduced anxiety-like behavior
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  31,38-39
Studies in PAC1 receptor–deficient mice suggest a protective role for the receptor in endotoxic shock.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  30
Decreased nociceptive response in PAC1 receptor-deficient mice in models of chronic inflammation
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24
When PAC1-deficient mice were crossed onto a C57BL/6 background, almost all mutants developed pulmonary hypertension and right heart failure after birth and died during the second postnatal week. These findings demonstrate the crucial importance of PAC1-mediated signaling for the maintenance of normal pulmonary vascular tone during early postnatal life.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
Mice lacking the PAC1 receptor or its ligand PACAP display an impairment in the ability of light pulses to induce phase shifts in circadian behaviour. PAC1 receptor null mice also displayed impaired masking (inhibition of wheel-running behaviour by light) at low light intensities.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7,18-19,26
Transgenic mice overexpressing the human PAC1 receptor in a pattern closely resembling that of the endogenous gene developed dose-dependent hydrocephalus-like characteristics, including enlarged third and lateral ventricles and reduced cerebral cortex, corpus callosum, and subcommissural organ (SCO). There was significantly reduced neuronal proliferation and massively increased neuronal apoptosis in the developing cortex and SCO of transgenic embryos, while neurite outgrowth and neuronal migration in vitro remained uncompromised.
Species:  Mouse
Tissue:  Brain
Technique:  Transgenic mice overexpressing the human PAC1 receptor
References:  29
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Adcyap1r1tm1.1Gsc Adcyap1r1tm1.1Gsc/Adcyap1r1tm1.1Gsc
involves: 129P2/OlaHsd
MGI:108449  MP:0001469 abnormal contextual conditioning behavior PMID: 11466423 
Adcyap1r1tm1.2Gsc|Tg(Camk2a-cre)1Gsc Adcyap1r1tm1.2Gsc/Adcyap1r1tm1.2Gsc,Tg(Camk2a-cre)1Gsc/0
involves: 129P2/OlaHsd * FVB/N
MGI:108449  MGI:2181421  MP:0001469 abnormal contextual conditioning behavior PMID: 11466423 
Adcyap1r1tm1.1Gsc Adcyap1r1tm1.1Gsc/Adcyap1r1tm1.1Gsc
involves: 129P2/OlaHsd
MGI:108449  MP:0001364 decreased anxiety-related response PMID: 11483244 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0001262 decreased body weight PMID: 10792006 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0002727 decreased circulating insulin level PMID: 10792006 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0002565 delayed circadian phase PMID: 11425915 
Adcyap1r1tm1.1Gsc Adcyap1r1tm1.1Gsc/Adcyap1r1tm1.1Gsc
involves: 129P2/OlaHsd
MGI:108449  MP:0001399 hyperactivity PMID: 11483244 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0005293 impaired glucose tolerance PMID: 10792006 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0002079 increased circulating insulin level PMID: 10792006 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0002412 increased susceptibility to bacterial infection PMID: 11792830 
Adcyap1r1tm1.2Gsc Adcyap1r1tm1.2Gsc/Adcyap1r1tm1.2Gsc
involves: 129P2/OlaHsd
MGI:108449  MP:0002169 no abnormal phenotype detected PMID: 11466423 
Adcyap1r1tm1Aba Adcyap1r1tm1Aba/Adcyap1r1tm1Aba
involves: C57BL/6
MGI:108449  MP:0002169 no abnormal phenotype detected PMID: 11032869 
Adcyap1r1tm1.1Gsc Adcyap1r1tm1.1Gsc/Adcyap1r1tm1.1Gsc
involves: 129P2/OlaHsd
MGI:108449  MP:0002082 postnatal lethality PMID: 11466423 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0002082 postnatal lethality PMID: 10792006 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0009011 prolonged diestrus PMID: 11193864 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0009006 prolonged estrous cycle PMID: 11193864 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0001923 reduced female fertility PMID: 11193864 
Adcyap1r1+|Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1+
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0001923 reduced female fertility PMID: 11193864 
Adcyap1r1tm1.1Gsc Adcyap1r1tm1.1Gsc/Adcyap1r1tm1.1Gsc
involves: 129P2/OlaHsd
MGI:108449  MP:0001473 reduced long term potentiation PMID: 11466423 
Adcyap1r1tm1Bbt Adcyap1r1tm1Bbt/Adcyap1r1tm1Bbt
involves: 129/Sv * C57BL/6J
MGI:108449  MP:0002563 shortened circadian period PMID: 11425915 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Post-traumatic stress disorder
References:  48
Click column headers to sort
Type Species Molecular location Description Reference
single nucleotide polymorphism Human C>G:- located in consensus sequence of putative estrogen response element (ERE) 48
Clinically-Relevant Mutations and Pathophysiology Comments
A single nucleotide polymorphism (dbSNP:rs2267735) in a putative oestrogen response element within ADCYAP1R1 has been reported to predict PTSD diagnosis and symptoms in females only
Biologically Significant Variants
Type:  Splice variants.
Species:  Rat
Description:  Within the part of the PAC1 receptor cDNA encoding the third intracellular loop, splice variants either containing or lacking each of two alternative exons ('hip' and 'hop') exist. The hop exon exists in two forms (hop1 and hop2) as the result of the presence of two alternative splice acceptor sites three nucleotides apart. Thus, six possible splice variants which differ in their intracellular signal transduction pathways can be generated.
References:  25,54
Type:  Splice variants.
Species:  Human
Description:  Four variants of the human PAC1 receptor (null, SV-1, SV-2 and SV-3) resulting from alternative splicing of sequences encoding part of the third intracellular loop (equivalent to hip and hop1 in the rat), have also been described and were shown to differ in their ability to activate phospholipase C (PLC).
References:  46
Type:  Splice variants.
Species:  Mouse
Description:  Splicing out of the 4th and 5th coding exons, leading to a 21aa-deletion in the N-terminal extracellular domain, influences receptor selectivity with respect to PACAP-27 and -38 binding and the relative potencies of the two agonists in phospholipase C stimulation.
References:  40
Type:  Splice variants.
Species:  Human
Description:  Splice variants with differing N-terminal extracellular domains were isolated from Y-79 retinoblastoma cells and human cerebellum. One variant named PAC1short (PAC1s) was deleted by 21 amino acids (residues 89-109) and bound PACAP38, PACAP27 and VIP with high affinity. A second novel variant, named PAC1 very short (PAC1vs), was deleted by 57 amino acids (residues 53-109) and preferentially bound PACAP38 (Ki=121 nM) and PACAP27 (Ki=129 nM) over VIP (Ki>1000 nM).
References:  9
Type:  Splice variants.
Species:  Rat
Description:  A splice variant PAC1R(3a) encoding a full-length receptor with the insertion of an additional 72 base pairs encoding 24 amino acids (exon 3a) between coding exons 3 and 4 was detected in seminiferous tubules, spermatids and Sertoli cells and also in astroctyes. There was a 6-fold increase in the affinity of the PAC1R(3a) to bind PACAP-38, and alterations in its coupling to both cAMP and inositol phosphate signaling pathways relative to the wild type PAC1 receptor.
References:  8,43
Available Assays
DiscoveRx PathHunter® CHO-K1 ADCYAP1R1 β-Arrestin Cell Line (Cat no. 93-0249C2)
PathHunter® eXpress ADCYAP1R1 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0249E2CP0M)
more info

REFERENCES

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To cite this database page, please use the following:

Anthony Harmar, Jan Fahrenkrug, Edward J. Goetzl, Illana Gozes, Marc Laburthe, Victor May, Joseph R. Pisegna, Sami I. Said, David Vaudry, Hubert Vaudry, James A. Waschek.
VIP and PACAP receptors: PAC1 receptor. Last modified on 14/06/2013. Accessed on 31/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=370.

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