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P18509

- PACA_HUMAN

UniProt

P18509 - PACA_HUMAN

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Protein

Pituitary adenylate cyclase-activating polypeptide

Gene

ADCYAP1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. neuropeptide hormone activity Source: UniProtKB
  2. peptide hormone receptor binding Source: UniProtKB
  3. pituitary adenylate cyclase activating polypeptide activity Source: BHF-UCL
  4. receptor binding Source: BHF-UCL
  5. receptor signaling protein activity Source: Ensembl

GO - Biological processi

  1. activation of adenylate cyclase activity Source: Reactome
  2. ATP metabolic process Source: Ensembl
  3. behavioral fear response Source: Ensembl
  4. cAMP-mediated signaling Source: UniProtKB
  5. cell-cell signaling Source: ProtInc
  6. cellular response to glucocorticoid stimulus Source: Ensembl
  7. female pregnancy Source: ProtInc
  8. histamine secretion Source: Ensembl
  9. negative regulation of acute inflammatory response to antigenic stimulus Source: Ensembl
  10. negative regulation of acute inflammatory response to non-antigenic stimulus Source: Ensembl
  11. negative regulation of cell cycle Source: Ensembl
  12. negative regulation of glial cell proliferation Source: Ensembl
  13. negative regulation of muscle cell apoptotic process Source: Ensembl
  14. negative regulation of potassium ion transport Source: Ensembl
  15. negative regulation of Rho GTPase activity Source: Ensembl
  16. neuron projection development Source: UniProtKB
  17. neuropeptide signaling pathway Source: UniProtKB
  18. neurotrophin TRK receptor signaling pathway Source: Reactome
  19. ovarian follicle development Source: Ensembl
  20. pituitary gland development Source: Ensembl
  21. positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Source: BHF-UCL
  22. positive regulation of cell proliferation Source: Ensembl
  23. positive regulation of cytosolic calcium ion concentration Source: Ensembl
  24. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  25. positive regulation of growth hormone secretion Source: Ensembl
  26. positive regulation of interleukin-6 production Source: Ensembl
  27. positive regulation of neuron projection development Source: Ensembl
  28. positive regulation of protein kinase activity Source: UniProtKB
  29. positive regulation of Rap GTPase activity Source: UniProtKB
  30. positive regulation of somatostatin secretion Source: Ensembl
  31. positive regulation of synaptic transmission, glutamatergic Source: Ensembl
  32. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  33. positive regulation of vasodilation Source: Ensembl
  34. regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
  35. regulation of oligodendrocyte progenitor proliferation Source: Ensembl
  36. regulation of postsynaptic membrane potential Source: Ensembl
  37. regulation of protein localization Source: BHF-UCL
  38. response to ethanol Source: Ensembl
  39. response to starvation Source: Ensembl
  40. sensory perception of pain Source: Ensembl
  41. transmembrane receptor protein tyrosine kinase signaling pathway Source: Reactome
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: Chromosome 18

Organism-specific databases

HGNCiHGNC:241. ADCYAP1.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: Ensembl
  3. 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.

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.
ExpressionAtlasiP18509. baseline and differential.
GenevestigatoriP18509.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi106629. 21 interactions.
DIPiDIP-60936N.
IntActiP18509. 2 interactions.
MINTiMINT-2801501.
STRINGi9606.ENSP00000269200.

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.
OMAiPPEKRHA.
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.

Polymorphism databases

DMDMi71159615.

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 .
CCDSi CCDS11825.1.
PIRi I84638.
RefSeqi NP_001093203.1. NM_001099733.1.
NP_001108.2. NM_001117.4.
UniGenei Hs.531719.
Hs.727476.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1GEA NMR - A 132-152 [» ]
2D2P NMR - A 132-169 [» ]
2JOD NMR - B 137-169 [» ]
ProteinModelPortali P18509.
SMRi P18509. Positions 132-169.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106629. 21 interactions.
DIPi DIP-60936N.
IntActi P18509. 2 interactions.
MINTi MINT-2801501.
STRINGi 9606.ENSP00000269200.

Chemistry

BindingDBi P18509.
ChEMBLi CHEMBL5692.

PTM databases

PhosphoSitei P18509.

Polymorphism databases

DMDMi 71159615.

Proteomic databases

PaxDbi P18509.
PRIDEi P18509.

Protocols and materials databases

DNASUi 116.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000450565 ; ENSP00000411658 ; ENSG00000141433 .
ENST00000579794 ; ENSP00000462647 ; ENSG00000141433 .
GeneIDi 116.
KEGGi hsa:116.
UCSCi uc010dkg.3. human.

Organism-specific databases

CTDi 116.
GeneCardsi GC18P000895.
HGNCi HGNC:241. ADCYAP1.
MIMi 102980. gene.
neXtProti NX_P18509.
PharmGKBi PA24564.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG39235.
GeneTreei ENSGT00530000063592.
HOVERGENi HBG018069.
InParanoidi P18509.
KOi K05262.
OMAi PPEKRHA.
OrthoDBi EOG7M6D8P.
PhylomeDBi P18509.
TreeFami TF332804.

Enzyme and pathway databases

Reactomei REACT_11046. NGF-independant TRKA activation.
REACT_18377. Glucagon-type ligand receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

EvolutionaryTracei P18509.
GeneWikii Pituitary_adenylate_cyclase-activating_peptide.
GenomeRNAii 116.
NextBioi 449.
PROi P18509.
SOURCEi Search...

Gene expression databases

Bgeei P18509.
CleanExi HS_ADCYAP1.
ExpressionAtlasi P18509. baseline and differential.
Genevestigatori P18509.

Family and domain databases

InterProi IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view ]
Pfami PF00123. Hormone_2. 2 hits.
[Graphical view ]
PRINTSi PR00275. GLUCAGON.
SMARTi SM00070. GLUCA. 2 hits.
[Graphical view ]
PROSITEi PS00260. GLUCAGON. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: November 26, 2014
This is version 134 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