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ADCYAP1 (adenylate cyclase activating polypeptide 1 (pituitary))

Written2014-09Terry Moody
National Cancer Institute, Center for Cancer Research, Office of the Director, 9609 Medical Center Drive, Rm 2W130, Bethesda, Maryland 20892, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesadenylate cyclase activating polypeptide 1 (pituitary)
Alias_symbol (synonym)PACAP
Other alias
HGNC (Hugo) ADCYAP1
LocusID (NCBI) 116
Atlas_Id 43656
Location 18p11.32  [Link to chromosome band 18p11]
Location_base_pair Starts at 904943 and ends at 912172 bp from pter ( according to hg19-Feb_2009)  [Mapping ADCYAP1.png]
Local_order The PACAP gene has 5 exons.
 
  Structure of human prepro-PACAP. Human prepro-PACAP (1-176) is metabolized by signal proteases to generate pro-PACAP (26-176). Pro-PACAP is metabolized by pro-hormone convertases to (26-79), big PACAP-related peptide (82-129; PRP) and PACAP-38. Pro-PACAP (26-176) can be further metabolized to PRP (82-109) and PACAP-27 by other enzymes.
PACAP is derived from the 176 amino acid precursor protein prepro-PACAP. Initially the signal peptide (1-25) is cleaved by signal proteases to generate pro-PACAP (26-176). Pro-PACAP is metabolized by pro-hormone convertases and carboxypeptidases to (26-79), (82-129) and (132-170). The C-terminal peptides (132-170) and (132-159) are metabolized to by peptidylglycine alpha-amidating monooxygenase enzymes to PACAP-38 and PACAP-27, respectively, which have amidated C-terminals.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note PACAP-27 or PACAP-38 are secreted proteins which binds to membrane G-protein coupled receptors (GPCR) increasing intracellular cAMP signaling.

DNA/RNA

Note The ADCYAP1 gene encodes 5 exons and is localized to chromosome 18p11 (Kimura et al., 1990). Exons 1 and 2 encode for the 5'UTR and the signal peptide. Exon 3 encodes for the N-terminal of pro-PACAP upstream from PRP. PRP is encoded by Exon 4. Exon 5 encodes for the C-terminal of pro-PACAP including PACAP-27, PACAP-38 and the 3'UTR (Vaudry et al., 2009).
Description The PACAP gene which contains 7230 bases is highly conserved in nature (Sherwood et al., 2000).
Transcription The gene transcript is 2.7 kb (Ghatei et al., 1993).

Protein

Note Pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated from ovine hypothalamus and contains 38 amino acids. PACAP-38 elevates cAMP in rat pituitary cells in culture (Miyata et al., 1989). PACAP-27 was isolated from ovine hypothalamus and had the same N-terminal 27 amino acids as does PACAP-38 (Miyata et al., 1990). PACAP-27 has high homology with vasoactive intestinal peptide (VIP) and moderate homology with PRP. The PACAP-38 amino acid sequence is identical in mammals. PACAP has a β-turn at residues 9-12, followed by an α-helix at residues 12-14, 15-20 and 22-24 (Inooka et al., 1992).
PACAP binds with high affinity to 3 GPCR (VPAC1, VPAC2 and PAC1) which are members of the class II or class B secretin-like receptors (Harmar et al., 2012). The activated VPAC1, VPAC2 or PAC1 interacts with a stimulatory guanine nucleotide binding protein (Gs) increasing adenylylcyclase activity resulting in elevated cAMP (Arimura et al., 1992). The increased cAMP activates protein kinase (PK) A causing phosphorylation of various proteins such as CREB leading to altered gene expression (Moody et al., 2003). In addition, PAC1 interacts with Gq causing phosphatidylinositol (PI) turnover (Pisegna and Wank, 1996). The resulting metabolites inositol-1,4,5-trisphosphate and diacylglycerol increases cytosolic calcium and activates protein kinase C, respectively.
Expression PACAP is produced in neurons within the adrenals, brain, gastrointestinal (GI) tract, pituitary and testis (Ghatei et al., 1993). Addition of PACAP to adrenal chormaffin cells causes catecholamine release (Watanabe et al., 1990). High densities of PACAP are present in the hypothalamus and PACAP as well as glutamate shift the circadian rhythm in the suprachiasmatic nucleus (Vaudry et al., 2009). In the gastrointestinal tract PACAP stimulates the secretion of saliva, gastric acid, bicarbonate and peptides leading to myorelaxation (Moody et al., 2011). In PACAP knockout mice or mice treated with PACAP(6-38) there is reduced insulin secretion after glucose challenge (Shintani et al., 2003). In pituitary cells, PACAP elevates cAMP increasing the secretion of LH, GH, PRL, ACTH and TSH (Vaudry et al., 2009). The results indicate that PACAP is present in the normal CNS and periphery.
Localisation Prepro-PACAP is stored in dense core neurosecretory granules in cells. In cellular extracts approximately an order of magnitude more PACAP-38 is detected than PRP or PACAP-27. PACAP-38 and PACAP-27 have approximately an order of magnitude more biological activity than does PRP (Fahrenkrug, 2010). PACAP is metabolized by neutral endopeptidase and has a half life of 5 min.
Function PACAP alters neurotransmitter release in the CNS, causes increased insulin and histamine secretion in the periphery, controls vasodilation, bronchodilation alters intestinal motility and stimulates cellular proliferation as well as differentiation (Vaudry et al., 2009).
Homology VIP has 67% sequence homology with PACAP-27. The sequence for PACAP-38 is identical in mammals (Fahrenkrug, 2010).

Mutations

Note Sequence mutations of PACAP-38 are rare. Numerous mutations of PAC1 have been reported including deletions, which affect PACAP binding (PAC1 short; PAC1 very short) and splice variants, which affect signal transduction (hip, hop1, hop2; Blechman and Levkowitz, 2013). SNP rs2267735 of PAC1 is associated with post-traumatic stress disorder (PTSD) in females (Ressler et al., 2011).

Implicated in

Note
  
Entity Lung cancer
Note PACAP-38 immunoreactivity is higher in the human lung cancer than normal lung biopsy specimens (Szanto et al., 2012). PAC1 is present in lung cancer cells and PACAP(6-38) inhibits their proliferation (Zia et al., 1995). PACAP-27 may stimulate lung cancer proliferation as a result of EGFR transactivation (Moody et al., 2012).
  
  
Entity Breast cancer
Note A 19.9 kDa prepro-PACAP was detected in human breast cancer biopsy specimens (Garcia Fernandez et al., 2004). PACAP-27 stimulated and PACAP(6-38) inhibited the growth of breast cancer cells (Leyton et al., 1999).
  
  
Entity Colon cancer
Note PACAP knockout mice but not wild type mice develop colitis and colorectal tumors after treatment with dextran sulfate sodium (Nemetz et al., 2008). PACAP-38 stimulates the growth of colon cancer cells (Le et al., 2002).
  
  
Entity Pheochromocytoma
Note PACAP increases the cAMP after addition to PC12 adrenal pheochromocytoma cells (Watanabe et al., 1990) and causes catecholamine secretion (Taupenot et al., 1999). PACAP addition to PC12 cells increases their survival as a result of Trk receptor tyrosine kinase phosphorylation and activation of Akt (Rajagopal et al., 2004).
  
  
Entity Pituitary adenoma
Note PACAP inhibits apoptosis caused by TGFβ addition to human pituitary adenoma cells (Oka et al., 1999). PAC1 receptor mRNA was present in all pituitary adenoma cells except prolactnomas (Oka et al., 1998).
  
  
Entity Medulloblastoma
Note Disruption of a single copy of the PACAP gene increased medulloblastoma incidence in ptc1 mutant mice 2.5-fold (Lelievre et al., 2008).
  
  
Entity Diabetes
Note ADCYAP1 stimulates insulin secretion in a glucose-dependent manner (Filipsson et al., 2001). Two SNPs g.9863G>A, G54D in exon 3, and g.12712C>G in exon 5 were found in European type 2 diabetic patients (Gu et al., 2002).
  
  
Entity Neuronal survival
Note PACAP stimulates neurite outgrowth and enhances neuronal cell survival (Canonico et al., 1996). PACAP addition to rat cerebellar neurites increases cAMP and inhibits caspase-3 activity (Vaudry et al., 2009).
  
  
Entity Schizophrenia
Note In PACAP knockout mice and schizophrenic patients, brain strathmin I is up-regulated (Hashimoto et al., 2007). PACAP reduces Strathmin I in animal models of schizophrenia by inhibiting the association of the DISCI-binding zinc-finger protein with DBZ (Katayama et al., 2009).
  

Bibliography

Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research.
Arimura A.
Regul Pept. 1992 Feb 18;37(3):287-303. (REVIEW)
PMID 1313597
 
Alternative Splicing of the Pituitary Adenylate Cyclase-Activating Polypeptide Receptor PAC1: Mechanisms of Fine Tuning of Brain Activity.
Blechman J, Levkowitz G.
Front Endocrinol (Lausanne). 2013 May 21;4:55. doi: 10.3389/fendo.2013.00055. eCollection 2013.
PMID 23734144
 
Activation of pituitary adenylate cyclase-activating polypeptide receptors prevents apoptotic cell death in cultured cerebellar granule cells.
Canonico PL, Copani A, D'Agata V, Musco S, Petralia S, Travali S, Stivala F, Cavallaro S.
Ann N Y Acad Sci. 1996 Dec 26;805:470-2.
PMID 8993425
 
VIP and PACAP.
Fahrenkrug J.
Results Probl Cell Differ. 2010;50:221-34. doi: 10.1007/400_2009_24. (REVIEW)
PMID 19859678
 
The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet function.
Filipsson K, Kvist-Reimer M, Ahren B.
Diabetes. 2001 Sep;50(9):1959-69. (REVIEW)
PMID 11522660
 
PACAP expression and distribution in human breast cancer and healthy tissue.
Garcia-Fernandez MO, Bodega G, Ruiz-Villaespesa A, Cortes J, Prieto JC, Carmena MJ.
Cancer Lett. 2004 Mar 18;205(2):189-95.
PMID 15036651
 
Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissues.
Ghatei MA, Takahashi K, Suzuki Y, Gardiner J, Jones PM, Bloom SR.
J Endocrinol. 1993 Jan;136(1):159-66.
PMID 8094091
 
Genetic variation screening and association studies of the adenylate cyclase activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes.
Gu HF.
Hum Mutat. 2002 May;19(5):572-3.
PMID 11968092
 
Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1.
Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V, Pisegna JR, Vaudry D, Vaudry H, Waschek JA, Said SI.
Br J Pharmacol. 2012 May;166(1):4-17. doi: 10.1111/j.1476-5381.2012.01871.x. (REVIEW)
PMID 22289055
 
Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia.
Hashimoto R, Hashimoto H, Shintani N, Chiba S, Hattori S, Okada T, Nakajima M, Tanaka K, Kawagishi N, Nemoto K, Mori T, Ohnishi T, Noguchi H, Hori H, Suzuki T, Iwata N, Ozaki N, Nakabayashi T, Saitoh O, Kosuga A, Tatsumi M, Kamijima K, Weinberger DR, Kunugi H, Baba A.
Mol Psychiatry. 2007 Nov;12(11):1026-32. Epub 2007 Mar 27.
PMID 17387318
 
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. 1992 Nov;40(5):456-64.
PMID 1483839
 
Role of the PACAP-PAC1-DISC1 and PACAP-PAC1-stathmin1 systems in schizophrenia and bipolar disorder: novel treatment mechanisms?
Katayama T, Hattori T, Yamada K, Matsuzaki S, Tohyama M.
Pharmacogenomics. 2009 Dec;10(12):1967-78. doi: 10.2217/pgs.09.147. (REVIEW)
PMID 19958095
 
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 RR, Stibbs HH, et al.
Biochem Biophys Res Commun. 1990 Jan 15;166(1):81-9.
PMID 2302217
 
PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumor cells.
Le SV, Yamaguchi DJ, McArdle CA, Tachiki K, Pisegna JR, Germano P.
Regul Pept. 2002 Nov 15;109(1-3):115-25.
PMID 12409223
 
Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice.
Lelievre V, Seksenyan A, Nobuta H, Yong WH, Chhith S, Niewiadomski P, Cohen JR, Dong H, Flores A, Liau LM, Kornblum HI, Scott MP, Waschek JA.
Dev Biol. 2008 Jan 1;313(1):359-70. Epub 2007 Nov 26.
PMID 18036580
 
PACAP(6-38) is a PACAP receptor antagonist for breast cancer cells.
Leyton J, Gozes Y, Pisegna J, Coy D, Purdom S, Casibang M, Zia F, Moody TW.
Breast Cancer Res Treat. 1999 Jul;56(2):177-86.
PMID 10573110
 
Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells.
Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH.
Biochem Biophys Res Commun. 1989 Oct 16;164(1):567-74.
PMID 2803320
 
Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38).
Miyata A, Jiang L, Dahl RD, Kitada C, Kubo K, Fujino M, Minamino N, Arimura A.
Biochem Biophys Res Commun. 1990 Jul 31;170(2):643-8.
PMID 2383262
 
Neuropeptides as autocrine growth factors in cancer cells.
Moody TW, Chan D, Fahrenkrug J, Jensen RT.
Curr Pharm Des. 2003;9(6):495-509. (REVIEW)
PMID 12570813
 
VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic studies.
Moody TW, Ito T, Osefo N, Jensen RT.
Curr Opin Endocrinol Diabetes Obes. 2011 Feb;18(1):61-7. doi: 10.1097/MED.0b013e328342568a. (REVIEW)
PMID 21157320
 
Pituitary adenylate cyclase-activating polypeptide causes tyrosine phosphorylation of the epidermal growth factor receptor in lung cancer cells.
Moody TW, Osefo N, Nuche-Berenguer B, Ridnour L, Wink D, Jensen RT.
J Pharmacol Exp Ther. 2012 Jun;341(3):873-81. doi: 10.1124/jpet.111.190033. Epub 2012 Mar 2.
PMID 22389426
 
Induction of colitis and rapid development of colorectal tumors in mice deficient in the neuropeptide PACAP.
Nemetz N, Abad C, Lawson G, Nobuta H, Chhith S, Duong L, Tse G, Braun J, Waschek JA.
Int J Cancer. 2008 Apr 15;122(8):1803-9.
PMID 18098289
 
Pituitary adenylate cyclase-activating polypeptide inhibits transforming growth factor-beta1-induced apoptosis in a human pituitary adenoma cell line.
Oka H, Jin L, Kulig E, Scheithauer BW, Lloyd RV.
Am J Pathol. 1999 Dec;155(6):1893-900.
PMID 10595920
 
Cloning and characterization of the signal transduction of four splice variants of the human pituitary adenylate cyclase activating polypeptide receptor. Evidence for dual coupling to adenylate cyclase and phospholipase C.
Pisegna JR, Wank SA.
J Biol Chem. 1996 Jul 19;271(29):17267-74.
PMID 8663363
 
Transactivation of Trk neurotrophin receptors by G-protein-coupled receptor ligands occurs on intracellular membranes.
Rajagopal R, Chen ZY, Lee FS, Chao MV.
J Neurosci. 2004 Jul 28;24(30):6650-8.
PMID 15282267
 
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor.
Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers AJ, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V.
Nature. 2011 Feb 24;470(7335):492-7. doi: 10.1038/nature09856.
PMID 21350482
 
The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily.
Sherwood NM, Krueckl SL, McRory JE.
Endocr Rev. 2000 Dec;21(6):619-70. (REVIEW)
PMID 11133067
 
Functional roles of the neuropeptide PACAP in brain and pancreas.
Shintani N, Tomimoto S, Hashimoto H, Kawaguchi C, Baba A.
Life Sci. 2003 Dec 5;74(2-3):337-43.
PMID 14607262
 
PACAP immunoreactivity in human malignant tumor samples and cardiac diseases.
Szanto Z, Sarszegi Z, Reglodi D, Nemeth J, Szabadfi K, Kiss P, Varga A, Banki E, Csanaky K, Gaszner B, Pinter O, Szalai Z, Tamas A.
J Mol Neurosci. 2012 Nov;48(3):667-73. Epub 2012 May 31.
PMID 22648511
 
Time-dependent effects of the neuropeptide PACAP on catecholamine secretion : stimulation and desensitization.
Taupenot L, Mahata M, Mahata SK, O'Connor DT.
Hypertension. 1999 Nov;34(5):1152-62.
PMID 10567198
 
Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery.
Vaudry D, Falluel-Morel A, Bourgault S, Basille M, Burel D, Wurtz O, Fournier A, Chow BK, Hashimoto H, Galas L, Vaudry H.
Pharmacol Rev. 2009 Sep;61(3):283-357. doi: 10.1124/pr.109.001370.(REVIEW)
PMID 19805477
 
Adrenal pheochromocytoma PC12h cells respond to pituitary adenylate cyclase activating polypeptide.
Watanabe T, Ohtaki T, Kitada C, Tsuda M, Fujino M.
Biochem Biophys Res Commun. 1990 Nov 30;173(1):252-8.
PMID 2175177
 
Pituitary adenylate cyclase activating peptide receptors regulate the growth of non-small cell lung cancer cells.
Zia F, Fagarasan M, Bitar K, Coy DH, Pisegna JR, Wank SA, Moody TW.
Cancer Res. 1995 Nov 1;55(21):4886-91.
PMID 7585525
 

Citation

This paper should be referenced as such :
Moody T
ADCYAP1 (adenylate cyclase activating polypeptide 1 (pituitary));
Atlas Genet Cytogenet Oncol Haematol. in press
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ADCYAP1ID43656ch18p11.html


External links

Nomenclature
HGNC (Hugo)ADCYAP1   241
Cards
AtlasADCYAP1ID43656ch18p11
Entrez_Gene (NCBI)ADCYAP1  116  adenylate cyclase activating polypeptide 1
AliasesPACAP
GeneCards (Weizmann)ADCYAP1
Ensembl hg19 (Hinxton)ENSG00000141433 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000141433 [Gene_View]  chr18:904943-912172 [Contig_View]  ADCYAP1 [Vega]
ICGC DataPortalENSG00000141433
TCGA cBioPortalADCYAP1
AceView (NCBI)ADCYAP1
Genatlas (Paris)ADCYAP1
WikiGenes116
SOURCE (Princeton)ADCYAP1
Genetics Home Reference (NIH)ADCYAP1
Genomic and cartography
GoldenPath hg38 (UCSC)ADCYAP1  -     chr18:904943-912172 +  18p11.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ADCYAP1  -     18p11.32   [Description]    (hg19-Feb_2009)
EnsemblADCYAP1 - 18p11.32 [CytoView hg19]  ADCYAP1 - 18p11.32 [CytoView hg38]
Mapping of homologs : NCBIADCYAP1 [Mapview hg19]  ADCYAP1 [Mapview hg38]
OMIM102980   
Gene and transcription
Genbank (Entrez)AB537500 AK294233 AK313050 BC093837 BC101803
RefSeq transcript (Entrez)NM_001099733 NM_001117
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ADCYAP1
Cluster EST : UnigeneHs.727476 [ NCBI ]
CGAP (NCI)Hs.727476
Alternative Splicing GalleryENSG00000141433
Gene ExpressionADCYAP1 [ NCBI-GEO ]   ADCYAP1 [ EBI - ARRAY_EXPRESS ]   ADCYAP1 [ SEEK ]   ADCYAP1 [ MEM ]
Gene Expression Viewer (FireBrowse)ADCYAP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)116
GTEX Portal (Tissue expression)ADCYAP1
Human Protein AtlasENSG00000141433-ADCYAP1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP18509   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP18509  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP18509
Splice isoforms : SwissVarP18509
PhosPhoSitePlusP18509
Domaine pattern : Prosite (Expaxy)GLUCAGON (PS00260)   
Domains : Interpro (EBI)Glucagon_GIP_secretin_VIP   
Domain families : Pfam (Sanger)Hormone_2 (PF00123)   
Domain families : Pfam (NCBI)pfam00123   
Domain families : Smart (EMBL)GLUCA (SM00070)  
Conserved Domain (NCBI)ADCYAP1
DMDM Disease mutations116
Blocks (Seattle)ADCYAP1
PDB (SRS)1GEA    2D2P    2JOD   
PDB (PDBSum)1GEA    2D2P    2JOD   
PDB (IMB)1GEA    2D2P    2JOD   
PDB (RSDB)1GEA    2D2P    2JOD   
Structural Biology KnowledgeBase1GEA    2D2P    2JOD   
SCOP (Structural Classification of Proteins)1GEA    2D2P    2JOD   
CATH (Classification of proteins structures)1GEA    2D2P    2JOD   
SuperfamilyP18509
Human Protein Atlas [tissue]ENSG00000141433-ADCYAP1 [tissue]
Peptide AtlasP18509
HPRD02369
IPIIPI01010404   IPI00000027   
Protein Interaction databases
DIP (DOE-UCLA)P18509
IntAct (EBI)P18509
FunCoupENSG00000141433
BioGRIDADCYAP1
STRING (EMBL)ADCYAP1
ZODIACADCYAP1
Ontologies - Pathways
QuickGOP18509
Ontology : AmiGOovarian follicle development  behavioral fear response  histamine secretion  negative regulation of acute inflammatory response to antigenic stimulus  negative regulation of acute inflammatory response to non-antigenic stimulus  signal transducer activity, downstream of receptor  receptor binding  neuropeptide hormone activity  protein binding  extracellular region  extracellular space  intracellular  activation of adenylate cyclase activity  positive regulation of cytosolic calcium ion concentration  neuropeptide signaling pathway  cell-cell signaling  female pregnancy  regulation of G-protein coupled receptor protein signaling pathway  positive regulation of cell proliferation  positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway  negative regulation of muscle cell apoptotic process  positive regulation of neuron projection development  pituitary adenylate cyclase activating polypeptide activity  sensory perception of pain  cAMP-mediated signaling  pituitary gland development  insulin secretion  neuron projection development  pituitary adenylate cyclase-activating polypeptide receptor binding  positive regulation of interleukin-6 production  regulation of protein localization  negative regulation of GTPase activity  response to starvation  terminal bouton  negative regulation of potassium ion transport  positive regulation of GTPase activity  response to ethanol  negative regulation of cell cycle  positive regulation of protein kinase activity  positive regulation of transcription from RNA polymerase II promoter  ATP metabolic process  peptide hormone receptor binding  peptide hormone receptor binding  positive regulation of synaptic transmission, glutamatergic  regulation of postsynaptic membrane potential  positive regulation of growth hormone secretion  negative regulation of glial cell proliferation  positive regulation of ERK1 and ERK2 cascade  regulation of oligodendrocyte progenitor proliferation  cellular response to glucocorticoid stimulus  positive regulation of chemokine (C-C motif) ligand 5 production  positive regulation of somatostatin secretion  positive regulation of blood vessel diameter  
Ontology : EGO-EBIovarian follicle development  behavioral fear response  histamine secretion  negative regulation of acute inflammatory response to antigenic stimulus  negative regulation of acute inflammatory response to non-antigenic stimulus  signal transducer activity, downstream of receptor  receptor binding  neuropeptide hormone activity  protein binding  extracellular region  extracellular space  intracellular  activation of adenylate cyclase activity  positive regulation of cytosolic calcium ion concentration  neuropeptide signaling pathway  cell-cell signaling  female pregnancy  regulation of G-protein coupled receptor protein signaling pathway  positive regulation of cell proliferation  positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway  negative regulation of muscle cell apoptotic process  positive regulation of neuron projection development  pituitary adenylate cyclase activating polypeptide activity  sensory perception of pain  cAMP-mediated signaling  pituitary gland development  insulin secretion  neuron projection development  pituitary adenylate cyclase-activating polypeptide receptor binding  positive regulation of interleukin-6 production  regulation of protein localization  negative regulation of GTPase activity  response to starvation  terminal bouton  negative regulation of potassium ion transport  positive regulation of GTPase activity  response to ethanol  negative regulation of cell cycle  positive regulation of protein kinase activity  positive regulation of transcription from RNA polymerase II promoter  ATP metabolic process  peptide hormone receptor binding  peptide hormone receptor binding  positive regulation of synaptic transmission, glutamatergic  regulation of postsynaptic membrane potential  positive regulation of growth hormone secretion  negative regulation of glial cell proliferation  positive regulation of ERK1 and ERK2 cascade  regulation of oligodendrocyte progenitor proliferation  cellular response to glucocorticoid stimulus  positive regulation of chemokine (C-C motif) ligand 5 production  positive regulation of somatostatin secretion  positive regulation of blood vessel diameter  
Pathways : KEGGInsulin secretion   
REACTOMEP18509 [protein]
REACTOME PathwaysR-HSA-420092 [pathway]   
NDEx NetworkADCYAP1
Atlas of Cancer Signalling NetworkADCYAP1
Wikipedia pathwaysADCYAP1
Orthology - Evolution
OrthoDB116
GeneTree (enSembl)ENSG00000141433
Phylogenetic Trees/Animal Genes : TreeFamADCYAP1
HOVERGENP18509
HOGENOMP18509
Homologs : HomoloGeneADCYAP1
Homology/Alignments : Family Browser (UCSC)ADCYAP1
Gene fusions - Rearrangements
Tumor Fusion PortalADCYAP1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerADCYAP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ADCYAP1
dbVarADCYAP1
ClinVarADCYAP1
1000_GenomesADCYAP1 
Exome Variant ServerADCYAP1
ExAC (Exome Aggregation Consortium)ENSG00000141433
GNOMAD BrowserENSG00000141433
Genetic variants : HAPMAP116
Genomic Variants (DGV)ADCYAP1 [DGVbeta]
DECIPHERADCYAP1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisADCYAP1 
Mutations
ICGC Data PortalADCYAP1 
TCGA Data PortalADCYAP1 
Broad Tumor PortalADCYAP1
OASIS PortalADCYAP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICADCYAP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDADCYAP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ADCYAP1
DgiDB (Drug Gene Interaction Database)ADCYAP1
DoCM (Curated mutations)ADCYAP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ADCYAP1 (select a term)
intoGenADCYAP1
NCG5 (London)ADCYAP1
Cancer3DADCYAP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM102980   
Orphanet
DisGeNETADCYAP1
MedgenADCYAP1
Genetic Testing Registry ADCYAP1
NextProtP18509 [Medical]
TSGene116
GENETestsADCYAP1
Target ValidationADCYAP1
Huge Navigator ADCYAP1 [HugePedia]
snp3D : Map Gene to Disease116
BioCentury BCIQADCYAP1
ClinGenADCYAP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD116
Chemical/Pharm GKB GenePA24564
Clinical trialADCYAP1
Miscellaneous
canSAR (ICR)ADCYAP1 (select the gene name)
Probes
Litterature
PubMed121 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineADCYAP1
EVEXADCYAP1
GoPubMedADCYAP1
iHOPADCYAP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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