ID PACR_HUMAN Reviewed; 468 AA. AC P41586; A8K1Y1; B7ZLA7; B8ZZK3; Q17S10; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-SEP-2026, entry version 213. DE RecName: Full=Pituitary adenylate cyclase-activating polypeptide type I receptor {ECO:0000303|PubMed:32047270}; DE Short=PAC1 receptor {ECO:0000303|PubMed:32047270}; DE Short=PAC1R {ECO:0000303|PubMed:32047270, ECO:0000303|PubMed:33715378}; DE Short=PACAP type I receptor; DE Short=PACAP-R-1; DE Short=PACAP-R1; DE Flags: Precursor; GN Name=ADCYAP1R1 {ECO:0000312|HGNC:HGNC:242}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM N). RC TISSUE=Pituitary; RX PubMed=7902709; DOI=10.1006/bbrc.1993.2423; RA Ogi K., Miyamoto Y., Masuda Y., Habata Y., Hosoya M., Ohtaki T., Masuo Y., RA Onda H., Fujino M.; RT "Molecular cloning and functional expression of a cDNA encoding a human RT pituitary adenylate cyclase activating polypeptide receptor."; RL Biochem. Biophys. Res. Commun. 196:1511-1521(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.; RT "Genome-wide discovery and analysis of human seven transmembrane helix RT receptor genes."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM N). RC TISSUE=Brain; RA King M., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM N). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM N-HOP1). RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 418-468. RC TISSUE=Placenta; RX PubMed=7851900; DOI=10.1006/geno.1994.1560; RA Stoffel M., Espinosa R., Trabb J.B., le Beau M.M., Bell G.I.; RT "Human type I pituitary adenylate cyclase activating polypeptide receptor RT (ADCYAP1R): localization to chromosome band 7p14 and integration into the RT cytogenetic, physical and genetic map of chromosome 7."; RL Genomics 23:697-699(1994). RN [9] RP ALTERNATIVE SPLICING. RX PubMed=10583729; DOI=10.1046/j.1365-2826.1999.00411.x; RA Dautzenberg F.M., Mevenkamp G., Wille S., Hauger R.L.; RT "N-terminal splice variants of the type I PACAP receptor: isolation, RT characterization and ligand binding/selectivity determinants."; RL J. Neuroendocrinol. 11:941-949(1999). RN [10] RP FUNCTION, AND MUTAGENESIS OF TYR-150. RX PubMed=35477937; DOI=10.1038/s41467-022-30041-z; RA Xu Y., Feng W., Zhou Q., Liang A., Li J., Dai A., Zhao F., Yan J., RA Chen C.W., Li H., Zhao L.H., Xia T., Jiang Y., Xu H.E., Yang D., Wang M.W.; RT "A distinctive ligand recognition mechanism by the human vasoactive RT intestinal polypeptide receptor 2."; RL Nat. Commun. 13:2272-2272(2022). RN [11] {ECO:0007744|PDB:2JOD} RP STRUCTURE BY NMR OF 22-143 IN COMPLEX WITH ADCYAP1, MUTAGENESIS OF VAL-114; RP GLU-125; PRO-128; GLU-138 AND TYR-139, AND DISULFIDE BONDS. RX PubMed=17470806; DOI=10.1073/pnas.0611397104; RA Sun C., Song D., Davis-Taber R.A., Barrett L.W., Scott V.E., RA Richardson P.L., Pereda-Lopez A., Uchic M.E., Solomon L.R., Lake M.R., RA Walter K.A., Hajduk P.J., Olejniczak E.T.; RT "Solution structure and mutational analysis of pituitary adenylate cyclase- RT activating polypeptide binding to the extracellular domain of PAC1-RS."; RL Proc. Natl. Acad. Sci. U.S.A. 104:7875-7880(2007). RN [12] {ECO:0007744|PDB:3N94} RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 26-140, MUTAGENESIS OF GLU-125, RP AND DISULFIDE BONDS. RX PubMed=21625560; DOI=10.1371/journal.pone.0019682; RA Kumar S., Pioszak A., Zhang C., Swaminathan K., Xu H.E.; RT "Crystal structure of the PAC1R extracellular domain unifies a consensus RT fold for hormone recognition by class B G-protein coupled receptors."; RL PLoS ONE 6:E19682-E19682(2011). RN [13] {ECO:0000312|PDB:6M1H, ECO:0007744|PDB:6M1I} RP STRUCTURE BY ELECTRON MICROSCOPY (3.6 ANGSTROMS) OF 23-438 MUTANT LEU-163; RP LEU-167; LEU-169; LEU-170; ALA-276; LEU-278 AND PHE-280 IN COMPLEX WITH RP ADCYAP1/PACAP-38 AND SAND FLY MAXADILAN, FUNCTION, INTERACTION WITH SAND RP FLY MAXADILAN, AND MUTAGENESIS OF TYR-130; PHE-131; TYR-157; TYR-161; RP ARG-199; LYS-206; ASP-207; MET-299; ASP-301; TRP-306; ARG-381; LEU-382 AND RP GLU-385. RX PubMed=32047270; DOI=10.1038/s41422-020-0280-2; RA Wang J., Song X., Zhang D., Chen X., Li X., Sun Y., Li C., Song Y., RA Ding Y., Ren R., Harrington E.H., Hu L.A., Zhong W., Xu C., Huang X., RA Wang H.W., Ma Y.; RT "Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism."; RL Cell Res. 30:436-445(2020). RN [14] {ECO:0007744|PDB:6P9Y} RP STRUCTURE BY ELECTRON MICROSCOPY (3.01 ANGSTROMS) OF 19-468 IN COMPLEX WITH RP ADCYAP1/PACAP-38; GNB1; GNG2 AND GNAS, AND FUNCTION. RX PubMed=32004469; DOI=10.1016/j.molcel.2020.01.012; RA Liang Y.L., Belousoff M.J., Zhao P., Koole C., Fletcher M.M., Truong T.T., RA Julita V., Christopoulos G., Xu H.E., Zhang Y., Khoshouei M., RA Christopoulos A., Danev R., Sexton P.M., Wootten D.; RT "Toward a structural understanding of class B GPCR peptide binding and RT activation."; RL Mol. Cell 77:656-668(2020). RN [15] {ECO:0000312|PDB:7JQD} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 18-143 IN COMPLEX WITH PEPTIDE RP ANTAGONIST, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=33715378; DOI=10.1021/acs.jmedchem.0c01396; RA Hu E., Hong F.T., Aral J., Long J., Piper D.E., Poppe L., Andrews K.L., RA Hager T., Davis C., Li H., Wong P., Gavva N., Shi L., Zhu D.X.D., RA Lehto S.G., Xu C., Miranda L.P.; RT "Discovery of Selective Pituitary Adenylate Cyclase 1 Receptor (PAC1R) RT Antagonist Peptides Potent in a Maxadilan/PACAP38-Induced Increase in Blood RT Flow Pharmacodynamic Model."; RL J. Med. Chem. 64:3427-3438(2021). RN [16] {ECO:0007744|PDB:8E3X} RP STRUCTURE BY ELECTRON MICROSCOPY (2.3 ANGSTROMS) OF 19-468 IN COMPLEX WITH RP ADCYAP1 AND G PROTEINS, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=36385145; DOI=10.1038/s41467-022-34629-3; RA Piper S.J., Deganutti G., Lu J., Zhao P., Liang Y.L., Lu Y., Fletcher M.M., RA Hossain M.A., Christopoulos A., Reynolds C.A., Danev R., Sexton P.M., RA Wootten D.; RT "Understanding VPAC receptor family peptide binding and selectivity."; RL Nat. Commun. 13:7013-7013(2022). CC -!- FUNCTION: G protein-coupled receptor activated by the neuropeptide CC pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP) CC (PubMed:32004469, PubMed:32047270, PubMed:33715378, PubMed:35477937, CC PubMed:36385145). Binds both PACAP27 and PACAP38 bioactive peptides CC (PubMed:32004469, PubMed:32047270, PubMed:35477937, PubMed:36385145). CC Ligand binding causes a conformation change that triggers signaling via CC guanine nucleotide-binding proteins (G proteins) and modulates the CC activity of downstream effectors. Activates cAMP-dependent pathway CC (PubMed:32004469, PubMed:32047270, PubMed:33715378, PubMed:35477937, CC PubMed:36385145). May regulate the release of adrenocorticotropin, CC luteinizing hormone, growth hormone, prolactin, epinephrine, and CC catecholamine. May play a role in spermatogenesis and sperm motility. CC Causes smooth muscle relaxation and secretion in the gastrointestinal CC tract (PubMed:32047270, PubMed:33715378). {ECO:0000269|PubMed:32004469, CC ECO:0000269|PubMed:32047270, ECO:0000269|PubMed:33715378, CC ECO:0000269|PubMed:35477937, ECO:0000269|PubMed:36385145}. CC -!- ACTIVITY REGULATION: Several synthetic peptides derived from maxadilan, CC a vasodilator peptide from Lutzomyia longipalpis saliva, act as CC antagonists for ADCYAP1R1. {ECO:0000269|PubMed:33715378}. CC -!- SUBUNIT: Interacts with maxadilan, a vasodilator peptide from Lutzomyia CC longipalpis saliva; the interaction results in ADCYAP1R1 activation CC (PubMed:32047270). {ECO:0000269|PubMed:17470806, CC ECO:0000269|PubMed:32047270, ECO:0000269|PubMed:36385145}. CC -!- INTERACTION: CC P41586-2; P05067: APP; NbExp=3; IntAct=EBI-17241711, EBI-77613; CC P41586-2; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-17241711, EBI-12837904; CC P41586-3; P18509: ADCYAP1; NbExp=2; IntAct=EBI-15635217, EBI-8588930; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein CC {ECO:0000269|PubMed:36385145}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=N; CC IsoId=P41586-1; Sequence=Displayed; CC Name=N-HOP1; CC IsoId=P41586-2; Sequence=VSP_042671; CC Name=S; CC IsoId=P41586-3; Sequence=VSP_042670; CC Name=S-HOP1; CC IsoId=P41586-4; Sequence=VSP_042670, VSP_042671; CC Name=VS; CC IsoId=P41586-5; Sequence=VSP_042669, VSP_042670; CC -!- TISSUE SPECIFICITY: Most abundant in the brain, low expression in the CC lung, liver, thymus, spleen, pancreas and placenta. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 2 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA04466.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D17516; BAA04466.1; ALT_INIT; mRNA. DR EMBL; AB065700; BAC05923.1; -; Genomic_DNA. DR EMBL; AY366498; AAQ72806.1; -; mRNA. DR EMBL; AK290046; BAF82735.1; -; mRNA. DR EMBL; AC006466; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC117116; AAI17117.1; -; mRNA. DR EMBL; BC136267; AAI36268.1; -; mRNA. DR EMBL; BC143679; AAI43680.1; -; mRNA. DR EMBL; CH471073; EAW93978.1; -; Genomic_DNA. DR EMBL; U09216; AAA19323.1; -; Genomic_DNA. DR CCDS; CCDS5433.1; -. [P41586-1] DR CCDS; CCDS56480.1; -. [P41586-2] DR CCDS; CCDS56481.1; -. [P41586-3] DR PIR; JN0902; JN0902. DR RefSeq; NP_001109.2; NM_001118.5. [P41586-1] DR RefSeq; NP_001186564.1; NM_001199635.2. [P41586-2] DR RefSeq; NP_001186565.1; NM_001199636.2. DR RefSeq; NP_001186566.1; NM_001199637.2. [P41586-3] DR RefSeq; XP_005249675.1; XM_005249618.6. [P41586-5] DR RefSeq; XP_016867226.1; XM_017011737.3. [P41586-4] DR RefSeq; XP_054213197.1; XM_054357222.1. [P41586-4] DR RefSeq; XP_054213200.1; XM_054357225.1. [P41586-5] DR PDB; 2JOD; NMR; -; A=22-143. DR PDB; 3N94; X-ray; 1.80 A; A=26-140. DR PDB; 6LPB; EM; 3.90 A; R=21-417. DR PDB; 6M1H; EM; 3.60 A; A=23-438. DR PDB; 6M1I; EM; 3.50 A; A=23-438. DR PDB; 6P9Y; EM; 3.01 A; R=19-468. DR PDB; 7JQD; X-ray; 2.70 A; A=18-143. DR PDB; 8E3X; EM; 2.30 A; R=19-468. DR PDB; 9P92; EM; 3.80 A; R=19-468. DR PDB; 9P93; EM; 3.20 A; R=19-468. DR PDB; 9P94; EM; 3.00 A; R=19-468. DR AlphaFoldDB; P41586; -. DR EMDB; EMD-0940; -. DR EMDB; EMD-20278; -. DR EMDB; EMD-27872; -. DR EMDB; EMD-30047; -. DR EMDB; EMD-30048; -. DR EMDB; EMD-71396; -. DR EMDB; EMD-71397; -. DR EMDB; EMD-71398; -. DR SMR; P41586; -. DR BioGRID; 106630; 3. DR CORUM; P41586; -. DR DIP; DIP-42467N; -. DR FunCoup; P41586; 554. DR IntAct; P41586; 6. DR MINT; P41586; -. DR NDEx; IQUERY-CP-ADCYAP1R1; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000483721; -. DR BindingDB; P41586; -. DR ChEMBL; CHEMBL5399; -. DR GuidetoPHARMACOLOGY; 370; -. DR TCDB; 9.A.14.4.8; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P41586; 5 sites, No reported glycans. DR GlyGen; P41586; 6 sites, 2 N-linked glycans (1 site). DR iPTMnet; P41586; -. DR PhosphoSitePlus; P41586; -. DR BioMuta; ADCYAP1R1; -. DR DMDM; 1171986; -. DR MassIVE; P41586; -. DR PaxDb; 9606-ENSP00000483721; -. DR PeptideAtlas; P41586; -. DR ProteomicsDB; 55465; -. [P41586-1] DR ProteomicsDB; 55466; -. [P41586-2] DR ProteomicsDB; 55467; -. [P41586-3] DR ProteomicsDB; 55468; -. [P41586-4] DR ProteomicsDB; 55469; -. [P41586-5] DR ABCD; P41586; 41 sequenced antibodies. DR Antibodypedia; 4280; 320 antibodies from 33 providers. DR DNASU; 117; -. DR Ensembl; ENST00000304166.9; ENSP00000306620.4; ENSG00000078549.17. [P41586-1] DR Ensembl; ENST00000396211.7; ENSP00000379514.2; ENSG00000078549.17. [P41586-2] DR Ensembl; ENST00000409363.5; ENSP00000387335.1; ENSG00000078549.17. [P41586-3] DR Ensembl; ENST00000705424.1; ENSP00000516125.1; ENSG00000078549.17. [P41586-2] DR Ensembl; ENST00000853916.1; ENSP00000523975.1; ENSG00000078549.17. [P41586-4] DR Ensembl; ENST00000853917.1; ENSP00000523976.1; ENSG00000078549.17. [P41586-5] DR GeneID; 117; -. DR KEGG; hsa:117; -. DR MANE-Select; ENST00000304166.9; ENSP00000306620.4; NM_001118.5; NP_001109.2. DR UCSC; uc003tca.3; human. [P41586-1] DR AGR; HGNC:242; -. DR ClinPGx; PA24565; -. DR CTD; 117; -. DR DisGeNET; 117; -. DR GeneCards; ADCYAP1R1; -. DR HGNC; HGNC:242; ADCYAP1R1. DR HPA; ENSG00000078549; Group enriched (brain, fallopian tube). DR MIM; 102981; gene. DR OpenTargets; ENSG00000078549; -. DR VEuPathDB; HostDB:ENSG00000078549; -. DR eggNOG; KOG4564; Eukaryota. DR GeneTree; ENSGT00940000157362; -. DR HOGENOM; CLU_002753_4_4_1; -. DR InParanoid; P41586; -. DR OrthoDB; 5967113at2759; -. DR PAN-GO; P41586; 4 GO annotations based on evolutionary models. DR PhylomeDB; P41586; -. DR PathwayCommons; P41586; -. DR Reactome; R-HSA-187024; NGF-independant TRKA activation. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-420092; Glucagon-type ligand receptors. DR SignaLink; P41586; -. DR SIGNOR; P41586; -. DR Agora; ENSG00000078549; -. DR BioGRID-ORCS; 117; 12 hits in 1139 CRISPR screens. DR ChiTaRS; ADCYAP1R1; human. DR EvolutionaryTrace; P41586; -. DR GeneWiki; ADCYAP1R1; -. DR GenomeRNAi; 117; -. DR Pharos; P41586; Tchem. DR PRO; PR:P41586; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P41586; protein. DR Bgee; ENSG00000078549; Expressed in cortical plate and 128 other cell types or tissues. DR ExpressionAtlas; P41586; baseline and differential. DR GO; GO:0005923; C:bicellular tight junction; IEA:Ensembl. DR GO; GO:0005901; C:caveola; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005768; C:endosome; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProt. DR GO; GO:0043235; C:signaling receptor complex; IDA:MGI. DR GO; GO:0008179; F:adenylate cyclase binding; IEA:Ensembl. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central. DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central. DR GO; GO:0001634; F:pituitary adenylate cyclase-activating polypeptide receptor activity; IDA:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl. DR GO; GO:0004999; F:vasoactive intestinal polypeptide receptor activity; IEA:InterPro. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006171; P:cAMP biosynthetic process; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0046545; P:development of primary female sexual characteristics; IEA:Ensembl. DR GO; GO:0033555; P:multicellular organismal response to stress; IEA:Ensembl. DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; IEA:Ensembl. DR GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; IEA:Ensembl. DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; IEA:Ensembl. DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR CDD; cd15987; 7tmB1_PACAP-R1; 1. DR FunFam; 1.20.1070.10:FF:000022; Pituitary adenylate cyclase-activating polypeptide type I receptor; 1. DR FunFam; 4.10.1240.10:FF:000008; pituitary adenylate cyclase-activating polypeptide type I receptor; 1. DR Gene3D; 4.10.1240.10; GPCR, family 2, extracellular hormone receptor domain; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR050332; GPCR_2. DR InterPro; IPR017981; GPCR_2-like_7TM. DR InterPro; IPR036445; GPCR_2_extracell_dom_sf. DR InterPro; IPR001879; GPCR_2_extracellular_dom. DR InterPro; IPR002285; GPCR_2_PACAP_1_rcpt. DR InterPro; IPR000832; GPCR_2_secretin-like. DR InterPro; IPR017983; GPCR_2_secretin-like_CS. DR PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 1. DR PANTHER; PTHR45620:SF12; PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE TYPE I RECEPTOR; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF02793; HRM; 1. DR PRINTS; PR00249; GPCRSECRETIN. DR PRINTS; PR01156; PACAPRECEPTR. DR SMART; SM00008; HormR; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF111418; Hormone receptor domain; 1. DR PROSITE; PS00649; G_PROTEIN_RECEP_F2_1; 1. DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1. DR PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR PDBsum; 2JOD; -. DR PDBsum; 3N94; -. DR PDBsum; 6LPB; -. DR PDBsum; 6M1H; -. DR PDBsum; 6M1I; -. DR PDBsum; 6P9Y; -. DR PDBsum; 7JQD; -. DR PDBsum; 8E3X; -. DR PDBsum; 9P92; -. DR PDBsum; 9P93; -. DR PDBsum; 9P94; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Developmental protein; KW Differentiation; Disulfide bond; G protein-coupled receptor; Glycoprotein; KW Membrane; Phosphoprotein; Proteomics identification; Receptor; KW Reference proteome; Signal; Spermatogenesis; Transducer; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..468 FT /note="Pituitary adenylate cyclase-activating polypeptide FT type I receptor" FT /id="PRO_0000012841" FT TOPO_DOM 21..152 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 153..177 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:36385145, ECO:0007744|PDB:6P9Y, FT ECO:0007744|PDB:8E3X" FT TOPO_DOM 178..187 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 188..208 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:36385145, ECO:0007744|PDB:6P9Y, FT ECO:0007744|PDB:8E3X" FT TOPO_DOM 209..223 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 224..249 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:36385145, ECO:0007744|PDB:6P9Y, FT ECO:0007744|PDB:8E3X" FT TOPO_DOM 250..267 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 268..290 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:36385145, ECO:0007744|PDB:6P9Y, FT ECO:0007744|PDB:8E3X" FT TOPO_DOM 291..302 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 303..329 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:36385145, ECO:0007744|PDB:6P9Y, FT ECO:0007744|PDB:8E3X" FT TOPO_DOM 330..347 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 348..374 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:36385145, ECO:0007744|PDB:6P9Y, FT ECO:0007744|PDB:8E3X" FT TOPO_DOM 375..379 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 380..403 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:32047270, ECO:0007744|PDB:6M1I, FT ECO:0007744|PDB:6P9Y" FT TOPO_DOM 404..468 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 125..139 FT /note="Important for ADCYAP1/PACAP ligand binding and FT specificity" FT /evidence="ECO:0000269|PubMed:17470806, FT ECO:0000269|PubMed:21625560" FT MOD_RES 434 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70205" FT MOD_RES 447 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70205" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 60 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 117 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 300 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 375 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 34..63 FT /evidence="ECO:0000269|PubMed:17470806, FT ECO:0000269|PubMed:21625560, ECO:0000269|PubMed:32047270, FT ECO:0000269|PubMed:33715378, ECO:0000269|PubMed:36385145, FT ECO:0007744|PDB:2JOD, ECO:0007744|PDB:3N94, FT ECO:0007744|PDB:6M1I, ECO:0007744|PDB:7JQD, FT ECO:0007744|PDB:8E3X" FT DISULFID 54..118 FT /evidence="ECO:0000269|PubMed:17470806, FT ECO:0000269|PubMed:21625560, ECO:0000269|PubMed:32047270, FT ECO:0000269|PubMed:33715378, ECO:0000269|PubMed:36385145, FT ECO:0007744|PDB:2JOD, ECO:0007744|PDB:3N94, FT ECO:0007744|PDB:6M1H, ECO:0007744|PDB:6M1I, FT ECO:0007744|PDB:7JQD, ECO:0007744|PDB:8E3X" FT DISULFID 77..134 FT /evidence="ECO:0000269|PubMed:17470806, FT ECO:0000269|PubMed:21625560, ECO:0000269|PubMed:32047270, FT ECO:0000269|PubMed:33715378, ECO:0000269|PubMed:36385145, FT ECO:0007744|PDB:2JOD, ECO:0007744|PDB:3N94, FT ECO:0007744|PDB:6M1H, ECO:0007744|PDB:7JQD, FT ECO:0007744|PDB:8E3X" FT DISULFID 226..296 FT /evidence="ECO:0000269|PubMed:32004469, FT ECO:0000269|PubMed:32047270, ECO:0000269|PubMed:36385145, FT ECO:0007744|PDB:6M1H, ECO:0007744|PDB:6M1I, FT ECO:0007744|PDB:6P9Y, ECO:0007744|PDB:8E3X" FT VAR_SEQ 53..88 FT /note="Missing (in isoform VS)" FT /evidence="ECO:0000305" FT /id="VSP_042669" FT VAR_SEQ 89..109 FT /note="Missing (in isoform S, isoform S-HOP1 and isoform FT VS)" FT /evidence="ECO:0000305" FT /id="VSP_042670" FT VAR_SEQ 348 FT /note="Y -> YFSCVQKCYCKPQRAQQHSCKMSELSTIT (in isoform FT N-HOP1 and isoform S-HOP1)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042671" FT MUTAGEN 114 FT /note="V->A: Reduced affinity for ADCYAP1." FT /evidence="ECO:0000269|PubMed:17470806" FT MUTAGEN 125 FT /note="E->R: Reduced affinity for ADCYAP1." FT /evidence="ECO:0000269|PubMed:17470806, FT ECO:0000269|PubMed:21625560" FT MUTAGEN 128 FT /note="P->A: Reduced affinity for ADCYAP1." FT /evidence="ECO:0000269|PubMed:17470806" FT MUTAGEN 130 FT /note="Y->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 131 FT /note="F->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 138 FT /note="E->R: Reduced affinity for ADCYAP1." FT /evidence="ECO:0000269|PubMed:17470806" FT MUTAGEN 139 FT /note="Y->A: Strongly reduced affinity for ADCYAP1." FT /evidence="ECO:0000269|PubMed:17470806" FT MUTAGEN 150 FT /note="Y->A: Decreased ADCYAP1/PACAP27 potency for FT ADCYAP1R1." FT /evidence="ECO:0000269|PubMed:35477937" FT MUTAGEN 157 FT /note="Y->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 161 FT /note="Y->A: Decreases PACAP-38-induced receptor activity FT in the functional cAMP assay. Decreases maxadilan-induced FT receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 199 FT /note="R->A: Decreases PACAP-38-induced receptor activity FT in the functional cAMP assay. Slightly decreases FT maxadilan-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 206 FT /note="K->A: Decreases PACAP-38-induced receptor activity FT in the functional cAMP assay. Decreases maxadilan-induced FT receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 207 FT /note="D->A: Decreases PACAP-38-induced receptor activity FT in the functional cAMP assay. Decreases maxadilan-induced FT receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 299 FT /note="M->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 301 FT /note="D->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 306 FT /note="W->A: Decreases PACAP-38-induced receptor activity FT in the functional cAMP assay. Decreases maxadilan-induced FT receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 381 FT /note="R->A: Decreases PACAP-38-induced receptor activity FT in the functional cAMP assay. Decreases maxadilan-induced FT receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 382 FT /note="L->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT MUTAGEN 385 FT /note="E->A: Decreases maxadilan-induced receptor activity FT in the functional cAMP assay. Does not affect FT PACAP-38-induced receptor activity." FT /evidence="ECO:0000269|PubMed:32047270" FT HELIX 26..47 FT /evidence="ECO:0007829|PDB:3N94" FT TURN 48..50 FT /evidence="ECO:0007829|PDB:2JOD" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:8E3X" FT STRAND 72..76 FT /evidence="ECO:0007829|PDB:3N94" FT HELIX 79..83 FT /evidence="ECO:0007829|PDB:3N94" FT STRAND 113..119 FT /evidence="ECO:0007829|PDB:3N94" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:3N94" FT HELIX 130..134 FT /evidence="ECO:0007829|PDB:3N94" FT HELIX 147..176 FT /evidence="ECO:0007829|PDB:8E3X" FT STRAND 178..180 FT /evidence="ECO:0007829|PDB:6M1I" FT HELIX 184..207 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 208..212 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 213..217 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 224..256 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 264..290 FT /evidence="ECO:0007829|PDB:8E3X" FT STRAND 294..299 FT /evidence="ECO:0007829|PDB:6M1I" FT HELIX 303..335 FT /evidence="ECO:0007829|PDB:8E3X" FT TURN 338..340 FT /evidence="ECO:0007829|PDB:8E3X" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 347..362 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 364..366 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 367..370 FT /evidence="ECO:0007829|PDB:8E3X" FT TURN 374..376 FT /evidence="ECO:0007829|PDB:6P9Y" FT HELIX 378..381 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 382..388 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 389..391 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 392..397 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 398..402 FT /evidence="ECO:0007829|PDB:8E3X" FT HELIX 405..416 FT /evidence="ECO:0007829|PDB:8E3X" FT CONFLICT P41586-2:350 FT /note="Missing (in Ref. 7; AAI43680)" FT /evidence="ECO:0000305" SQ SEQUENCE 468 AA; 53314 MW; BB515B84E9F28977 CRC64; MAGVVHVSLA ALLLLPMAPA MHSDCIFKKE QAMCLEKIQR ANELMGFNDS SPGCPGMWDN ITCWKPAHVG EMVLVSCPEL FRIFNPDQVW ETETIGESDF GDSNSLDLSD MGVVSRNCTE DGWSEPFPHY FDACGFDEYE SETGDQDYYY LSVKALYTVG YSTSLVTLTT AMVILCRFRK LHCTRNFIHM NLFVSFMLRA ISVFIKDWIL YAEQDSNHCF ISTVECKAVM VFFHYCVVSN YFWLFIEGLY LFTLLVETFF PERRYFYWYT IIGWGTPTVC VTVWATLRLY FDDTGCWDMN DSTALWWVIK GPVVGSIMVN FVLFIGIIVI LVQKLQSPDM GGNESSIYLR LARSTLLLIP LFGIHYTVFA FSPENVSKRE RLVFELGLGS FQGFVVAVLY CFLNGEVQAE IKRKWRSWKV NRYFAVDFKH RHPSLASSGV NGGTQLSILS KSSSQIRMSG LPADNLAT //