P18509 (PACA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pituitary adenylate cyclase-activating polypeptide
Short name=PACAP

Cleaved into the following 3 chains:

1. PACAP-related peptide
   Alternative name(s):
   PRP-48
2. Pituitary adenylate cyclase-activating polypeptide 27
   Short name=PACAP-27
   Short name=PACAP27
3. Pituitary adenylate cyclase-activating polypeptide 38
   Short name=PACAP-38
   Short name=PACAP38

Gene names

Name:

ADCYAP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	176 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	Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells. Ref.8
Subunit structure	Interacts with ADCYAP1R1 (via N-terminal extracellular domain).
Subcellular location	Secreted.
Sequence similarities	Belongs to the glucagon family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP metabolic process Inferred from electronic annotation. Source: Compara activation of adenylate cyclase activity Traceable author statement. Source: Reactome behavioral fear response Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement Ref.5. Source: ProtInc cellular response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara female pregnancy Traceable author statement PubMed 10698193. Source: ProtInc histamine secretion Inferred from electronic annotation. Source: Compara negative regulation of Rho GTPase activity Inferred from electronic annotation. Source: Compara negative regulation of acute inflammatory response to antigenic stimulus Inferred from electronic annotation. Source: Compara negative regulation of acute inflammatory response to non-antigenic stimulus Inferred from electronic annotation. Source: Compara negative regulation of cell cycle Inferred from electronic annotation. Source: Compara negative regulation of glial cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of potassium ion transport Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome ovarian follicle development Inferred from electronic annotation. Source: Compara pituitary gland development Inferred from electronic annotation. Source: Compara positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 9603988. Source: BHF-UCL positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of growth hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of interleukin-6 production Inferred from electronic annotation. Source: Compara positive regulation of neuron projection development Inferred from electronic annotation. Source: Compara positive regulation of somatostatin secretion Inferred from electronic annotation. Source: Compara positive regulation of synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara positive regulation of vasodilation Inferred from electronic annotation. Source: Compara regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay Ref.8. Source: UniProtKB regulation of oligodendrocyte progenitor proliferation Inferred from electronic annotation. Source: Compara regulation of postsynaptic membrane potential Inferred from electronic annotation. Source: Compara regulation of protein localization Inferred from direct assay PubMed 9603988. Source: BHF-UCL response to ethanol Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara sensory perception of pain Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara terminal bouton Inferred from electronic annotation. Source: Compara
Molecular_function	neuropeptide hormone activity Traceable author statement Ref.5. Source: ProtInc peptide hormone receptor binding Inferred from direct assay Ref.8. Source: UniProtKB pituitary adenylate cyclase activating polypeptide activity Inferred from direct assay PubMed 9603988. Source: BHF-UCL receptor signaling protein activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Propeptide

25 – 79

55

PRO_0000011486

Peptide

82 – 129

48

PACAP-related peptide

PRO_0000011487

Peptide

132 – 169

38

Pituitary adenylate cyclase-activating polypeptide 38

PRO_0000011488

Peptide

132 – 158

27

Pituitary adenylate cyclase-activating polypeptide 27

PRO_0000011489

Propeptide

173 – 176

4

PRO_0000011490

Regions

Region

150 – 158

9

Important for receptor binding

Amino acid modifications

Modified residue

158

1

Leucine amide

Modified residue

169

1

Lysine amide

Natural variations

Natural variant

54

1

D → G. Ref.1 Ref.2 Ref.3 Ref.10
Corresponds to variant rs2856966 [ dbSNP | Ensembl ].

VAR_014597

Experimental info

Mutagenesis

150

1

V → G: Strongly reduced affinity for ADCYAP1R1. Ref.9

Mutagenesis

151

1

K → E: Strongly reduced affinity for ADCYAP1R1. Ref.9

Mutagenesis

152

1

K → E: Strongly reduced affinity for ADCYAP1R1. Ref.9

Mutagenesis

153

1

Y → A: Strongly reduced affinity for ADCYAP1R1. Ref.9

Mutagenesis

157

1

V → A: Strongly reduced affinity for ADCYAP1R1. Ref.9

Mutagenesis

158

1

L → A: Strongly reduced affinity for ADCYAP1R1. Ref.9

Secondary structure

1

.

.

.

.

.

.

176

Helix Strand Turn

Details...

Beta strand

135 – 139

5

Helix

140 – 150

11

Helix

153 – 160

8

Sequences

	Sequence		Length	Mass (Da)
	P18509 [UniParc]. Last modified May 10, 2005. Version 3. Checksum: 696DD57D2A510E1D	FASTA	176	18,835
	10 20 30 40 50 60 MTMCSGARLA LLVYGIIMHS SVYSSPAAAG LRFPGIRPEE EAYGEDGNPL PDFDGSEPPG 70 80 90 100 110 120 AGSPASAPRA AAAWYRPAGR RDVAHGILNE AYRKVLDQLS AGKHLQSLVA RGVGGSLGGG 130 140 150 160 170 AGDDAEPLSK RHSDGIFTDS YSRYRKQMAV KKYLAAVLGK RYKQRVKNKG RRIAYL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and characterization of the precursor to human pituitary adenylate cyclase activating polypeptide." Ohkubo S., Kimura C., Ogi K., Okazaki K., Hosoya M., Onda H., Miyata A., Arimura A., Fujino M. DNA Cell Biol. 11:21-30(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-54. Tissue: Testis.
[2]	"Structure of the human pituitary adenylate cyclase activating polypeptide (PACAP) gene." Hosoya M., Kimura C., Ogi K., Ohkubo S., Miyamoto Y., Kugoh H., Shimizu M., Onda H., Oshimura M., Arimura A., Fujino M. Biochim. Biophys. Acta 1129:199-206(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-54.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-54. Tissue: Brain.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"A novel peptide which stimulates adenylate cyclase: molecular cloning and characterization of the ovine and human cDNAs." Kimura C., Ohkubo S., Ogi K., Hosoya M., Itoh Y., Onda H., Miyata A., Jiang L., Dahl R.R., Stibbs H.H., Arimura A., Fujino M. Biochem. Biophys. Res. Commun. 166:81-89(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 114-176.
[6]	"Solution structure of pituitary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy." Wray V., Kakoschke C., Nokihara K., Naruse S. Biochemistry 32:5832-5841(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 132-169.
[7]	"Pituitary adenylate cyclase activating polypeptide (PACAP) with 27 residues. Conformation determined by 1H NMR and CD spectroscopies and distance geometry in 25% methanol solution." Inooka H., Endo S., Kitada C., Mizuta E., Fujino M. Int. J. Pept. Protein Res. 40:456-464(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 132-158.
[8]	"Conformation of a peptide ligand bound to its G-protein coupled receptor." Inooka H., Ohtaki T., Kitahara O., Ikegami T., Endo S., Kitada C., Ogi K., Onda H., Fujino M., Shirakawa M. Nat. Struct. Biol. 8:161-165(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 132-152, FUNCTION.
[9]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 137-169 IN COMPLEX WITH ADCYAP1R1, MUTAGENESIS OF VAL-150; LYS-151; LYS-152; TYR-153; VAL-157 AND LEU-158.
[10]	"Genetic variation screening and association studies of the adenylate cyclase activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes." Gu H.F. Hum. Mutat. 19:572-573(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLY-54.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S83513 mRNA. Translation: AAB21470.1.
X60435 Genomic DNA. Translation: CAA42962.1.
AK313050 mRNA. Translation: BAG35881.1.
BC093837 mRNA. Translation: AAH93837.1.
BC101803 mRNA. Translation: AAI01804.1.

IPI

IPI01010404.

PIR

I84638.

RefSeq

NP_001093203.1. NM_001099733.1.
NP_001108.2. NM_001117.4.

UniGene

Hs.531719.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GEA	NMR	-	A	132-152	[»]
2D2P	NMR	-	A	132-169	[»]
2JOD	NMR	-	B	137-169	[»]

ProteinModelPortal

P18509.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000269200.

PTM databases

PhosphoSite

P18509.

Polymorphism databases

DMDM

71159615.

Proteomic databases

PaxDb

P18509.

PRIDE

P18509.

Protocols and materials databases

DNASU

116.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000450565; ENSP00000411658; ENSG00000141433.
ENST00000579794; ENSP00000462647; ENSG00000141433.

GeneID

116.

KEGG

hsa:116.

UCSC

uc010dkg.3. human.

Organism-specific databases

CTD

116.

GeneCards

GC18P000895.

HGNC

HGNC:241. ADCYAP1.

MIM

102980. gene.

neXtProt

NX_P18509.

PharmGKB

PA24564.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39235.

HOVERGEN

HBG018069.

InParanoid

P18509.

KO

K05262.

OrthoDB

EOG4Q58QM.

PhylomeDB

P18509.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P18509.

Bgee

P18509.

CleanEx

HS_ADCYAP1.

Genevestigator

P18509.

GermOnline

ENSG00000141433. Homo sapiens.

Family and domain databases

InterPro

IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]

Pfam

PF00123. Hormone_2. 2 hits.
[Graphical view]

PRINTS

PR00275. GLUCAGON.

SMART

SM00070. GLUCA. 2 hits.
[Graphical view]

PROSITE

PS00260. GLUCAGON. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P18509.

ChEMBL

CHEMBL5692.

EvolutionaryTrace

P18509.

GenomeRNAi

116.

NextBio

449.

SOURCE

Search...

Entry information

Entry name

PACA_HUMAN

Accession

Primary (citable) accession number: P18509
Secondary accession number(s): B2R7N4, Q52LQ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	May 10, 2005
Last modified:	May 1, 2013
This is version 119 of the entry and version 3 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.