Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P18509 (PACA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length176 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells. Promotes neuron projection development through the RAPGEF2/Rap1/B-Raf/ERK pathway. Ref.6 Ref.9

Subunit structure

Interacts with ADCYAP1R1 (via N-terminal extracellular domain).

Subcellular location

Secreted.

Sequence similarities

Belongs to the glucagon family.

Ontologies

Keywords
   Biological processNeurogenesis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Cleavage on pair of basic residues
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP metabolic process

Inferred from electronic annotation. Source: Ensembl

activation of adenylate cyclase activity

Traceable author statement. Source: Reactome

behavioral fear response

Inferred from electronic annotation. Source: Ensembl

cAMP-mediated signaling

Inferred from mutant phenotype Ref.6. Source: UniProtKB

cell-cell signaling

Traceable author statement Ref.5. Source: ProtInc

cellular response to glucocorticoid stimulus

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Traceable author statement PubMed 10698193. Source: ProtInc

histamine secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of Rho GTPase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of acute inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of acute inflammatory response to non-antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of glial cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from direct assay Ref.6. Source: UniProtKB

neuropeptide signaling pathway

Inferred from direct assay Ref.6. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

pituitary gland development

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of Rap GTPase activity

Inferred from direct assay Ref.6. Source: UniProtKB

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: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of growth hormone secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase activity

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of somatostatin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of vasodilation

Inferred from electronic annotation. Source: Ensembl

regulation of G-protein coupled receptor protein signaling pathway

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of oligodendrocyte progenitor proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of protein localization

Inferred from direct assay PubMed 9603988. Source: BHF-UCL

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to starvation

Inferred from electronic annotation. Source: Ensembl

sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

terminal bouton

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionneuropeptide hormone activity

Inferred from direct assay Ref.6. Source: UniProtKB

peptide hormone receptor binding

Inferred from direct assay Ref.9. Source: UniProtKB

pituitary adenylate cyclase activating polypeptide activity

Inferred from direct assay PubMed 9603988. Source: BHF-UCL

receptor binding

Inferred from physical interaction PubMed 7680413. Source: BHF-UCL

receptor signaling protein activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 7955
PRO_0000011486
Peptide82 – 12948PACAP-related peptide
PRO_0000011487
Peptide132 – 16938Pituitary adenylate cyclase-activating polypeptide 38
PRO_0000011488
Peptide132 – 15827Pituitary adenylate cyclase-activating polypeptide 27
PRO_0000011489
Propeptide173 – 1764
PRO_0000011490

Regions

Region150 – 1589Important for receptor binding

Amino acid modifications

Modified residue1581Leucine amide
Modified residue1691Lysine amide

Natural variations

Natural variant541D → G. Ref.1 Ref.2 Ref.3 Ref.11
Corresponds to variant rs2856966 [ dbSNP | Ensembl ].
VAR_014597

Experimental info

Mutagenesis1501V → G: Strongly reduced affinity for ADCYAP1R1. Ref.10
Mutagenesis1511K → E: Strongly reduced affinity for ADCYAP1R1. Ref.10
Mutagenesis1521K → E: Strongly reduced affinity for ADCYAP1R1. Ref.10
Mutagenesis1531Y → A: Strongly reduced affinity for ADCYAP1R1. Ref.10
Mutagenesis1571V → A: Strongly reduced affinity for ADCYAP1R1. Ref.10
Mutagenesis1581L → A: Strongly reduced affinity for ADCYAP1R1. Ref.10

Secondary structure

...... 176
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P18509 [UniParc].

Last modified May 10, 2005. Version 3.
Checksum: 696DD57D2A510E1D

FASTA17618,835
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal and Endocrine Cells."
Emery A.C., Eiden M.V., Mustafa T., Eiden L.E.
Sci. Signal. 6:RA51-RA51(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
PIRI84638.
RefSeqNP_001093203.1. NM_001099733.1.
NP_001108.2. NM_001117.4.
UniGeneHs.531719.
Hs.727476.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GEANMR-A132-152[»]
2D2PNMR-A132-169[»]
2JODNMR-B137-169[»]
ProteinModelPortalP18509.
SMRP18509. Positions 132-169.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106629. 2 interactions.
IntActP18509. 2 interactions.
MINTMINT-2801501.
STRING9606.ENSP00000269200.

Chemistry

BindingDBP18509.
ChEMBLCHEMBL5692.

PTM databases

PhosphoSiteP18509.

Polymorphism databases

DMDM71159615.

Proteomic databases

PaxDbP18509.
PRIDEP18509.

Protocols and materials databases

DNASU116.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000450565; ENSP00000411658; ENSG00000141433.
ENST00000579794; ENSP00000462647; ENSG00000141433.
GeneID116.
KEGGhsa:116.
UCSCuc010dkg.3. human.

Organism-specific databases

CTD116.
GeneCardsGC18P000895.
HGNCHGNC:241. ADCYAP1.
MIM102980. gene.
neXtProtNX_P18509.
PharmGKBPA24564.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39235.
HOVERGENHBG018069.
InParanoidP18509.
KOK05262.
OMARYRQRIR.
OrthoDBEOG7M6D8P.
PhylomeDBP18509.
TreeFamTF332804.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP18509.
BgeeP18509.
CleanExHS_ADCYAP1.
GenevestigatorP18509.

Family and domain databases

InterProIPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PfamPF00123. Hormone_2. 2 hits.
[Graphical view]
PRINTSPR00275. GLUCAGON.
SMARTSM00070. GLUCA. 2 hits.
[Graphical view]
PROSITEPS00260. GLUCAGON. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP18509.
GeneWikiPituitary_adenylate_cyclase-activating_peptide.
GenomeRNAi116.
NextBio449.
PROP18509.
SOURCESearch...

Entry information

Entry namePACA_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 127 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM