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Protein

Pituitary adenylate cyclase-activating polypeptide

Gene

ADCYAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  • neuropeptide hormone activity Source: UniProtKB
  • peptide hormone receptor binding Source: UniProtKB
  • pituitary adenylate cyclase activating polypeptide activity Source: BHF-UCL
  • receptor binding Source: BHF-UCL
  • receptor signaling protein activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hormone

Keywords - Biological processi

Neurogenesis

Enzyme and pathway databases

ReactomeiREACT_11046. NGF-independant TRKA activation.
REACT_18377. Glucagon-type ligand receptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Pituitary adenylate cyclase-activating polypeptide
Short name:
PACAP
Cleaved into the following 3 chains:
Alternative name(s):
PRP-48
Pituitary adenylate cyclase-activating polypeptide 27
Short name:
PACAP-27
Short name:
PACAP27
Pituitary adenylate cyclase-activating polypeptide 38
Short name:
PACAP-38
Short name:
PACAP38
Gene namesi
Name:ADCYAP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:241. ADCYAP1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: GOC
  • extracellular region Source: Reactome
  • extracellular space Source: Ensembl
  • intracellular Source: GOC
  • terminal bouton Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi150 – 1501V → G: Strongly reduced affinity for ADCYAP1R1. 1 Publication
Mutagenesisi151 – 1511K → E: Strongly reduced affinity for ADCYAP1R1. 1 Publication
Mutagenesisi152 – 1521K → E: Strongly reduced affinity for ADCYAP1R1. 1 Publication
Mutagenesisi153 – 1531Y → A: Strongly reduced affinity for ADCYAP1R1. 1 Publication
Mutagenesisi157 – 1571V → A: Strongly reduced affinity for ADCYAP1R1. 1 Publication
Mutagenesisi158 – 1581L → A: Strongly reduced affinity for ADCYAP1R1. 1 Publication

Organism-specific databases

PharmGKBiPA24564.

Polymorphism and mutation databases

BioMutaiADCYAP1.
DMDMi71159615.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Propeptidei25 – 7955PRO_0000011486Add
BLAST
Peptidei82 – 12948PACAP-related peptidePRO_0000011487Add
BLAST
Peptidei132 – 16938Pituitary adenylate cyclase-activating polypeptide 38PRO_0000011488Add
BLAST
Peptidei132 – 15827Pituitary adenylate cyclase-activating polypeptide 27PRO_0000011489Add
BLAST
Propeptidei173 – 1764PRO_0000011490

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei158 – 1581Leucine amide1 Publication
Modified residuei169 – 1691Lysine amide1 Publication

Keywords - PTMi

Amidation, Cleavage on pair of basic residues

Proteomic databases

PaxDbiP18509.
PRIDEiP18509.

PTM databases

PhosphoSiteiP18509.

Expressioni

Gene expression databases

BgeeiP18509.
CleanExiHS_ADCYAP1.
GenevisibleiP18509. HS.

Interactioni

Subunit structurei

Interacts with ADCYAP1R1 (via N-terminal extracellular domain).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CLUP109094EBI-8588930,EBI-1104674

Protein-protein interaction databases

BioGridi106629. 17 interactions.
DIPiDIP-60936N.
IntActiP18509. 3 interactions.
MINTiMINT-2801501.
STRINGi9606.ENSP00000411658.

Structurei

Secondary structure

1
176
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi135 – 1395Combined sources
Helixi140 – 15011Combined sources
Helixi153 – 1608Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GEANMR-A132-152[»]
2D2PNMR-A132-169[»]
2JODNMR-B137-169[»]
ProteinModelPortaliP18509.
SMRiP18509. Positions 132-169.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP18509.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni150 – 1589Important for receptor binding

Sequence similaritiesi

Belongs to the glucagon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39235.
GeneTreeiENSGT00530000063592.
HOVERGENiHBG018069.
InParanoidiP18509.
KOiK05262.
OMAiADGIFNK.
OrthoDBiEOG7M6D8P.
PhylomeDBiP18509.
TreeFamiTF332804.

Family and domain databases

InterProiIPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PfamiPF00123. Hormone_2. 2 hits.
[Graphical view]
PRINTSiPR00275. GLUCAGON.
SMARTiSM00070. GLUCA. 2 hits.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P18509-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTMCSGARLA LLVYGIIMHS SVYSSPAAAG LRFPGIRPEE EAYGEDGNPL
60 70 80 90 100
PDFDGSEPPG AGSPASAPRA AAAWYRPAGR RDVAHGILNE AYRKVLDQLS
110 120 130 140 150
AGKHLQSLVA RGVGGSLGGG AGDDAEPLSK RHSDGIFTDS YSRYRKQMAV
160 170
KKYLAAVLGK RYKQRVKNKG RRIAYL
Length:176
Mass (Da):18,835
Last modified:May 10, 2005 - v3
Checksum:i696DD57D2A510E1D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti54 – 541D → G.4 Publications
Corresponds to variant rs2856966 [ dbSNP | Ensembl ].
VAR_014597

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11825.1.
PIRiI84638.
RefSeqiNP_001093203.1. NM_001099733.1.
NP_001108.2. NM_001117.4.
UniGeneiHs.531719.
Hs.727476.

Genome annotation databases

EnsembliENST00000450565; ENSP00000411658; ENSG00000141433.
ENST00000579794; ENSP00000462647; ENSG00000141433.
GeneIDi116.
KEGGihsa:116.
UCSCiuc010dkg.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11825.1.
PIRiI84638.
RefSeqiNP_001093203.1. NM_001099733.1.
NP_001108.2. NM_001117.4.
UniGeneiHs.531719.
Hs.727476.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GEANMR-A132-152[»]
2D2PNMR-A132-169[»]
2JODNMR-B137-169[»]
ProteinModelPortaliP18509.
SMRiP18509. Positions 132-169.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106629. 17 interactions.
DIPiDIP-60936N.
IntActiP18509. 3 interactions.
MINTiMINT-2801501.
STRINGi9606.ENSP00000411658.

Chemistry

BindingDBiP18509.
ChEMBLiCHEMBL5692.

PTM databases

PhosphoSiteiP18509.

Polymorphism and mutation databases

BioMutaiADCYAP1.
DMDMi71159615.

Proteomic databases

PaxDbiP18509.
PRIDEiP18509.

Protocols and materials databases

DNASUi116.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000450565; ENSP00000411658; ENSG00000141433.
ENST00000579794; ENSP00000462647; ENSG00000141433.
GeneIDi116.
KEGGihsa:116.
UCSCiuc010dkg.3. human.

Organism-specific databases

CTDi116.
GeneCardsiGC18P000895.
HGNCiHGNC:241. ADCYAP1.
MIMi102980. gene.
neXtProtiNX_P18509.
PharmGKBiPA24564.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39235.
GeneTreeiENSGT00530000063592.
HOVERGENiHBG018069.
InParanoidiP18509.
KOiK05262.
OMAiADGIFNK.
OrthoDBiEOG7M6D8P.
PhylomeDBiP18509.
TreeFamiTF332804.

Enzyme and pathway databases

ReactomeiREACT_11046. NGF-independant TRKA activation.
REACT_18377. Glucagon-type ligand receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

EvolutionaryTraceiP18509.
GeneWikiiPituitary_adenylate_cyclase-activating_peptide.
GenomeRNAii116.
NextBioi449.
PROiP18509.
SOURCEiSearch...

Gene expression databases

BgeeiP18509.
CleanExiHS_ADCYAP1.
GenevisibleiP18509. HS.

Family and domain databases

InterProiIPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PfamiPF00123. Hormone_2. 2 hits.
[Graphical view]
PRINTSiPR00275. GLUCAGON.
SMARTiSM00070. GLUCA. 2 hits.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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, AMIDATION AT LEU-158 AND LYS-169.
  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.

Entry informationi

Entry nameiPACA_HUMAN
AccessioniPrimary (citable) accession number: P18509
Secondary accession number(s): B2R7N4, Q52LQ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: May 10, 2005
Last modified: June 24, 2015
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.