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P18509

- PACA_HUMAN

UniProt

P18509 - PACA_HUMAN

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
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 3 (10 May 2005)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiP18509.
    BgeeiP18509.
    CleanExiHS_ADCYAP1.
    GenevestigatoriP18509.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi106629. 2 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 – 1395
    Helixi140 – 15011
    Helixi153 – 1608

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MTMCSGARLA LLVYGIIMHS SVYSSPAAAG LRFPGIRPEE EAYGEDGNPL    50
    PDFDGSEPPG AGSPASAPRA AAAWYRPAGR RDVAHGILNE AYRKVLDQLS 100
    AGKHLQSLVA RGVGGSLGGG AGDDAEPLSK RHSDGIFTDS YSRYRKQMAV 150
    KKYLAAVLGK RYKQRVKNKG RRIAYL 176
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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. 2 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.
    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

    ArrayExpressi P18509.
    Bgeei P18509.
    CleanExi HS_ADCYAP1.
    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

    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: October 1, 2014
    This is version 132 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