Pituitary adenylate cyclase-activating peptide

Technopedia Center

Faculty of Engineering and Computer Science
S1 Informatics S1 Information Systems S1 Information Technology S1 Computer Engineering S1 Electrical Engineering S1 Civil Engineering

faculty of Economics and Business
S1 Management S1 Accountancy

Faculty of Letters and Educational Sciences
S1 English literature S1 English language education S1 Mathematics education S1 Sports Education

Pituitary adenylate cyclase-activating peptide - Wikipedia

From Wikipedia, the free encyclopedia

(Redirected from Pituitary adenylate cyclase activating peptide)

ADCYAP1

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
1GEA, 2D2P, 2JOD

Identifiers

Aliases

ADCYAP1, PACAP, adenylate cyclase activating polypeptide 1

External IDs

OMIM: 102980; MGI: 105094; HomoloGene: 869; GeneCards: ADCYAP1; OMA:ADCYAP1 - orthologs

Gene location (Human)

Chr.	Chromosome 18 (human)^[1]

Band	18p11.32	Start	904,871 bp^[1]
Band	18p11.32	End	912,172 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 17 (mouse)^[2]

Band	17\|17 E5	Start	93,506,445 bp^[2]
Band	17\|17 E5	End	93,513,965 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

beta cell

gonad

Hypothalamus

prefrontal cortex

Brodmann area 9

gallbladder

cingulate gyrus

ganglionic eminence

anterior cingulate cortex

right frontal lobe

Top expressed in

lumbar spinal ganglion

mammillary body

ventromedial nucleus

ventral tegmental area

dorsomedial hypothalamic nucleus

trigeminal ganglion

habenula

central gray substance of midbrain

primary visual cortex

superior frontal gyrus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	pituitary adenylate cyclase activating polypeptide activity hormone activity peptide hormone receptor binding protein binding pituitary adenylate cyclase-activating polypeptide receptor binding neuropeptide hormone activity signaling receptor binding
Cellular component	intracellular anatomical structure extracellular region terminal bouton extracellular space neuron projection perikaryon cell body fiber
Biological process	histamine secretion pituitary gland development regulation of G protein-coupled receptor signaling pathway negative regulation of glial cell proliferation female pregnancy cell-cell signaling negative regulation of cell cycle negative regulation of muscle cell apoptotic process behavioral fear response nervous system development activation of adenylate cyclase activity regulation of protein localization positive regulation of GTPase activity ATP metabolic process negative regulation of acute inflammatory response to non-antigenic stimulus regulation of oligodendrocyte progenitor proliferation cellular response to glucocorticoid stimulus positive regulation of gene expression negative regulation of GTPase activity positive regulation of synaptic transmission, glutamatergic positive regulation of chemokine (C-C motif) ligand 5 production regulation of postsynaptic membrane potential positive regulation of cell population proliferation negative regulation of potassium ion transport positive regulation of ERK1 and ERK2 cascade positive regulation of interleukin-6 production positive regulation of neuron projection development response to starvation ovarian follicle development sensory perception of pain response to ethanol negative regulation of acute inflammatory response to antigenic stimulus neuropeptide signaling pathway neuron projection development cAMP-mediated signaling positive regulation of somatostatin secretion positive regulation of transcription by RNA polymerase II positive regulation of protein kinase activity regulation of protein phosphorylation positive regulation of cytosolic calcium ion concentration insulin secretion positive regulation of growth hormone secretion regulation of signaling receptor activity G protein-coupled receptor signaling pathway adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of cAMP-mediated signaling brain development camera-type eye development positive regulation of cold-induced thermogenesis
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


116


11516

Ensembl


ENSG00000141433


ENSMUSG00000024256

UniProt


P18509


O70176

RefSeq (mRNA)


NM_001099733 NM_001117


NM_009625 NM_001315503 NM_001315504

RefSeq (protein)


NP_001093203 NP_001108


NP_001302432 NP_001302433 NP_033755

Location (UCSC)

Chr 18: 0.9 – 0.91 Mb

Chr 17: 93.51 – 93.51 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene.^[5]^[6] pituitary adenylate cyclase-activating polypeptide is similar to vasoactive intestinal peptide. One of its effects is to stimulate enterochromaffin-like cells. It binds to vasoactive intestinal peptide receptor and to the pituitary adenylate cyclase-activating polypeptide receptor.

Function

This gene encodes adenylate cyclase-activating polypeptide 1. Mediated by adenylate cyclase-activating polypeptide 1 receptors, this polypeptide stimulates adenylate cyclase and subsequently increases the cAMP level in target cells. Adenylate cyclase-activating polypeptide 1 not only is a hypophysiotropic hormone (i.e. a substance that induces activity in the hypophysis), but also functions as a neurotransmitter and neuromodulator. In addition, it plays a role in paracrine and autocrine regulation of certain types of cells. This gene has five exons. Exons 1 and 2 encode the 5' UTR and signal peptide, respectively; exon 4 encodes an adenylate cyclase-activating polypeptide 1-related peptide; and exon 5 encodes the mature peptide and 3' UTR. This gene encodes three different mature peptides, including two isotypes: a shorter form and a longer form.^[6]

A version of this gene has been associated with post-traumatic stress disorder (PTSD) in women (but not men).^[7] This disorder involves a maladaptive psychological response to traumatic, i.e. existence-threatening, events. Ressler et al. identified an association of a SNP in the gene coding for pituitary adenylate cyclase-activating polypeptide (PACAP), implicating this peptide and its receptor (PAC1) in PTSD. In mouse model of heavy alcohol drinking, PACAP seems to mediate alcohol effects on bed nucleus of the stria terminalis.^[8]

Headache Disorders

Both isoforms of pituitary adenylate cyclase-activating polypeptide (pituitary adenylate cyclase-activating polypeptide-38 and pituitary adenylate cyclase-activating polypeptide-27) have been implicated in migraine pathogenesis.^[9]^[10] A Danish research group led by Dr. Messoud Ashina found that intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 induced migraine attacks in 58% of people with migraine,^[9] whilst the corresponding migraine induction rate was 55% for pituitary adenylate cyclase-activating polypeptide-27.^[10] Treatments with monoclonal antibodies have been investigated to target pituitary adenylate cyclase-activating polypeptide or its receptors for the treatment of primary headache disorders. Alder BioPharmaceuticals's ALD1910, which targets the peptide, began a phase I study in October 2019.^[11]^[12] Amgen's AMG-301, which targets the PAC1 receptor, failed to show greater efficacy than placebo in phase II trials.^[13]

Interactions

Pituitary adenylate cyclase-activating peptide has been shown to interact with secretin receptor.^[14]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000141433 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024256 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Hosoya M, Kimura C, Ogi K, Ohkubo S, Miyamoto Y, Kugoh H, et al. (January 1992). "Structure of the human pituitary adenylate cyclase activating polypeptide (PACAP) gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1129 (2): 199–206. doi:10.1016/0167-4781(92)90488-l. PMID 1730060.
^ ^a ^b "Entrez Gene: ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary)".
^ Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, et al. (February 2011). "Post-traumatic stress disorder is associated with pituitary adenylate cyclase-activating polypeptide and the PAC1 receptor". Nature. 470 (7335): 492–7. Bibcode:2011Natur.470..492R. doi:10.1038/nature09856. PMC 3046811. PMID 21350482.
^ Lauren Lepeak ... (1 December 2023). "Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice". eNeuro. 10 (12). doi:10.1523/ENEURO.0424-23.2023. PMC 10755645. PMID 38053471.
^ ^a ^b Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M (January 2009). "pituitary adenylate cyclase-activating polypeptide-38 induces migraine-like attacks in patients with migraine without aura". Brain. 132 (Pt 1): 16–25. doi:10.1093/brain/awn307. PMID 19052139.
^ ^a ^b Ghanizada H, Al-Karagholi MA, Arngrim N, Olesen J, Ashina M (January 2020). "PACAP27 induces migraine-like attacks in migraine patients". Cephalalgia. 40 (1): 57–67. doi:10.1177/0333102419864507. PMID 31299857. S2CID 196349669.
^ Bertels Z, Pradhan AA (July 2019). "Emerging Treatment Targets for Migraine and Other Headaches". Headache. 59 Suppl 2 (S2): 50–65. doi:10.1111/head.13585. PMC 6986366. PMID 31291018.
^ "Alder BioPharmaceuticals® Announces First-in-Human Dosing in Phase 1 ALD1910 Study for Preventive Treatment of Migraine". Globenewswire News Room. GlobeNewswire. 10 October 2019. Retrieved 10 October 2019.
^ Ashina M, Doležil D, Bonner JH, Zhou L, Klatt J, Picard H, Mikol DD (January 2021). "A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention". Cephalalgia. 41 (1): 33–44. doi:10.1177/0333102420970889. PMC 7786389. PMID 33231489.
^ Felley CP, Qian JM, Mantey S, Pradhan T, Jensen RT (December 1992). "Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release". The American Journal of Physiology. 263 (6 Pt 1): G901-7. doi:10.1152/ajpgi.1992.263.6.G901. PMID 1335692.

External links

Pituitary+adenylate+cyclase-activating+polypeptide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

v t e PDB gallery
2d2p: The solution structure of micelle-bound peptide 2jod: Pac1-Rshort N-terminal EC domain Pacap(6-38) complex

Peptides: neuropeptides

Hormones

see hormones

Opioid peptides

Dynorphins	Dynorphin A Dynorphin A_1–8 Dynorphin B Big dynorphin Leumorphin α-Neoendorphin β-Neoendorphin
Endomorphins	Endomorphin-1 Endomorphin-2
Endorphins	α-Endorphin β-Endorphin γ-Endorphin
Enkephalins	Met-enkephalin Leu-enkephalin
Others	Adrenorphin Amidorphin Hemorphin Hemorphin-4 Nociceptin Opiorphin Spinorphin Valorphin

Other
neuropeptides

Kinins	Bradykinins Tachykinins: mammal Substance P Neurokinin A Neurokinin B amphibian Kassinin Physalaemin
Neuromedins	B N S U
Orexins	A B
Other	Angiotensin Bombesin Calcitonin gene-related peptide Carnosine Cocaine- and amphetamine-regulated transcript Delta-sleep-inducing peptide FMRFamide Galanin Galanin-like peptide Gastrin-releasing peptide Ghrelin Neuropeptide AF Neuropeptide FF Neuropeptide SF Neuropeptide VF Neuropeptide S Neuropeptide Y Neurophysins Neurotensin Pancreatic polypeptide Pituitary adenylate cyclase-activating peptide RVD-Hpα VGF

v t e Cell signaling: Nervous tissue: Neurotrophic factors
Neurotrophins	NGF BDNF NT-3 NT-4
GDNF family	GDNF Artemin Neurturin Persephin
Ephrins	A1 A2 A3 A4 A5 B1 B2 B3
CNTF family	CNTF LIF IL-6
Other	GMF IGF-1 Neuregulins 1 2 3 4 PACAP VEGF

Growth factor receptor modulators

Angiopoietin

Agonists: Angiopoietin 1
Angiopoietin 4

Antagonists: Angiopoietin 2
Angiopoietin 3

Kinase inhibitors: Altiratinib
CE-245677
Rebastinib

Antibodies: Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

Agonists: Axokine
CNTF
Dapiclermin

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors: Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Selpercatinib Trafermin Velafermin
FGFR2	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin Kinase inhibitors: Infigratinib
FGFR3	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Selpercatinib Sprifermin Trafermin Antibodies: Burosumab (against FGF23)
FGFR4	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin
Unsorted	Agonists: FGF15/19

HGF (c-Met)

Agonists: Fosgonimeton
Hepatocyte growth factor

Potentiators: Dihexa (PNB-0408)

IGF

IGF-1	Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors: BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies: AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antibodies: Against NGF: ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers: Against NGF: RBM-004

Decoy receptors: LEVI-04 (p75^NTR-Fc)

PDGF

Agonists: Becaplermin
Platelet-derived growth factor (A, B, C, D)

RET (GFL)

GFRα1	Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib
GFRα2	Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib
GFRα3	Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib
GFRα4	Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib
Unsorted	Kinase inhibitors: Agerafenib

SCF (c-Kit)

Agonists: Ancestim
Stem cell factor

TGFβ

See here instead.

Trk

TrkA	Agonists: Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists: ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators: VM-902A Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers: Against NGF: RBM-004 Decoy receptors: ReN-1820 (TrkAd5)
TrkB	Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands: DHEA Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists: BNN-20 DHEA NT-3 Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486