P41586 (PACR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pituitary adenylate cyclase-activating polypeptide type I receptor
Short name=PACAP type I receptor
Short name=PACAP-R-1
Short name=PACAP-R1

Gene names

Name:

ADCYAP1R1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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.
Subunit structure	Interacts (via N-terminal extracellular domain) with ADCYAP1.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Most abundant in the brain, low expression in the lung, liver, thymus, spleen, pancreas and placenta.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.
Sequence caution	The sequence BAA04466.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Cell membrane Membrane
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of adenylate cyclase activity Traceable author statement. Source: Reactome cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	vasoactive intestinal polypeptide receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 468

448

Pituitary adenylate cyclase-activating polypeptide type I receptor

PRO_0000012841

Regions

Topological domain

21 – 155

135

Extracellular Potential

Transmembrane

156 – 178

23

Helical; Name=1; Potential

Topological domain

179 – 186

8

Cytoplasmic Potential

Transmembrane

187 – 205

19

Helical; Name=2; Potential

Topological domain

206 – 227

22

Extracellular Potential

Transmembrane

228 – 253

26

Helical; Name=3; Potential

Topological domain

254 – 268

15

Cytoplasmic Potential

Transmembrane

269 – 291

23

Helical; Name=4; Potential

Topological domain

292 – 309

18

Extracellular Potential

Transmembrane

310 – 332

23

Helical; Name=5; Potential

Topological domain

333 – 350

18

Cytoplasmic Potential

Transmembrane

351 – 371

21

Helical; Name=6; Potential

Topological domain

372 – 385

14

Extracellular Potential

Transmembrane

386 – 405

20

Helical; Name=7; Potential

Topological domain

406 – 468

63

Cytoplasmic Potential

Region

125 – 139

15

Important for ligand binding and specificity

Amino acid modifications

Glycosylation

48

1

N-linked (GlcNAc...) Potential

Glycosylation

60

1

N-linked (GlcNAc...) Potential

Glycosylation

117

1

N-linked (GlcNAc...) Potential

Glycosylation

300

1

N-linked (GlcNAc...) Potential

Glycosylation

375

1

N-linked (GlcNAc...) Potential

Disulfide bond

34 ↔ 63

Ref.7

Disulfide bond

54 ↔ 118

Ref.7

Disulfide bond

77 ↔ 134

Ref.7

Experimental info

Mutagenesis

114

1

V → A: Reduced affinity for ADCYAP1. Ref.7

Mutagenesis

125

1

E → R: Reduced affinity for ADCYAP1. Ref.7

Mutagenesis

128

1

P → A: Reduced affinity for ADCYAP1. Ref.7

Mutagenesis

138

1

E → R: Reduced affinity for ADCYAP1. Ref.7

Mutagenesis

139

1

Y → A: Strongly reduced affinity for ADCYAP1. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

468

Helix Strand Turn

Details...

Helix

24 – 26

3

Helix

30 – 44

15

Turn

48 – 50

3

Beta strand

73 – 75

3

Beta strand

114 – 116

3

Sequences

	Sequence		Length	Mass (Da)
	P41586 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: BB515B84E9F28977	FASTA	468	53,314
	10 20 30 40 50 60 MAGVVHVSLA ALLLLPMAPA MHSDCIFKKE QAMCLEKIQR ANELMGFNDS SPGCPGMWDN 70 80 90 100 110 120 ITCWKPAHVG EMVLVSCPEL FRIFNPDQVW ETETIGESDF GDSNSLDLSD MGVVSRNCTE 130 140 150 160 170 180 DGWSEPFPHY FDACGFDEYE SETGDQDYYY LSVKALYTVG YSTSLVTLTT AMVILCRFRK 190 200 210 220 230 240 LHCTRNFIHM NLFVSFMLRA ISVFIKDWIL YAEQDSNHCF ISTVECKAVM VFFHYCVVSN 250 260 270 280 290 300 YFWLFIEGLY LFTLLVETFF PERRYFYWYT IIGWGTPTVC VTVWATLRLY FDDTGCWDMN 310 320 330 340 350 360 DSTALWWVIK GPVVGSIMVN FVLFIGIIVI LVQKLQSPDM GGNESSIYLR LARSTLLLIP 370 380 390 400 410 420 LFGIHYTVFA FSPENVSKRE RLVFELGLGS FQGFVVAVLY CFLNGEVQAE IKRKWRSWKV 430 440 450 460 NRYFAVDFKH RHPSLASSGV NGGTQLSILS KSSSQIRMSG LPADNLAT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of a cDNA encoding a human pituitary adenylate cyclase activating polypeptide receptor." Ogi K., Miyamoto Y., Masuda Y., Habata Y., Hosoya M., Ohtaki T., Masuo Y., Onda H., Fujino M. Biochem. Biophys. Res. Commun. 196:1511-1521(1993) [PubMed: 7902709] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pituitary.
[2]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." King M., Aronstam R.S., Sharma S.V. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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." Stoffel M., Espinosa R., Trabb J.B., le Beau M.M., Bell G.I. Genomics 23:697-699(1994) [PubMed: 7851900] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 418-468. Tissue: Placenta.
[7]	"Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS." Sun C., Song D., Davis-Taber R.A., Barrett L.W., Scott V.E., Richardson P.L., Pereda-Lopez A., Uchic M.E., Solomon L.R., Lake M.R., Walter K.A., Hajduk P.J., Olejniczak E.T. Proc. Natl. Acad. Sci. U.S.A. 104:7875-7880(2007) [PubMed: 17470806] [Abstract] Cited for: STRUCTURE BY NMR OF 22-143 IN COMPLEX WITH ADCYAP1, MUTAGENESIS OF VAL-114; GLU-125; PRO-128; GLU-138 AND TYR-139, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D17516 mRNA. Translation: BAA04466.1. Different initiation.
AB065700 Genomic DNA. Translation: BAC05923.1.
AY366498 mRNA. Translation: AAQ72806.1.
AK290046 mRNA. Translation: BAF82735.1.
CH471073 Genomic DNA. Translation: EAW93978.1.
U09216 Genomic DNA. Translation: AAA19323.1.

IPI

IPI00299406.

PIR

JN0902.

RefSeq

NP_001109.2. NM_001118.4.

UniGene

Hs.377783.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JOD	NMR	-	A	22-143	[»]
3N94	X-ray	1.80	A	26-140	[»]

ProteinModelPortal

P41586.

SMR

P41586. Positions 26-140.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1217291.

STRING

P41586.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P41586.

Polymorphism databases

DMDM

1171986.

Proteomic databases

PRIDE

P41586.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000304166; ENSP00000306620; ENSG00000078549.

GeneID

117.

KEGG

hsa:117.

UCSC

uc003tca.1. human.

Organism-specific databases

CTD

117.

GeneCards

GC07P031058.

H-InvDB

HIX0006574.

HGNC

HGNC:242. ADCYAP1R1.

MIM

102981. gene.

neXtProt

NX_P41586.

PharmGKB

PA24565.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16465.

GeneTree

ENSGT00580000081259.

HOVERGEN

HBG008318.

OrthoDB

EOG4B5P5B.

PhylomeDB

P41586.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P41586.

Bgee

P41586.

CleanEx

HS_ADCYAP1R1.

Genevestigator

P41586.

GermOnline

ENSG00000078549. Homo sapiens.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR002285. GPCR_2_PACAP_1_rcpt.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

KO

K04587.

PANTHER

PTHR12011:SF30. PAC_1_rcpt. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR00249. GPCRSECRETIN.
PR01156. PACAPRECEPTR.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

455.

SOURCE

Search...

Entry information

Entry name

PACR_HUMAN

Accession

Primary (citable) accession number: P41586
Secondary accession number(s): A8K1Y1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	December 14, 2011
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.