Target Information
Target General Information | Top | |||||
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Target ID |
T07045
(Former ID: TTDI02210)
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Target Name |
Pituitary adenylate cyclase-activating 38 (PACAP-38)
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Synonyms |
Pituitary adenylate cyclase-activating polypeptide; PACAP38; PACAP27; PACAP-38; PACAP-27; PACAP; ADCYAP1
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Gene Name |
ADCYAP1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Unspecific body region injury [ICD-11: ND56] | |||||
Function |
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.
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BioChemical Class |
Glucagon
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UniProt ID | ||||||
Sequence |
HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQRVKNK
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T94HUW |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | PACAP38 | Drug Info | Phase 1 | Nerve injury | [2], [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | PACAP38 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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cAMP signaling pathway | hsa04024 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Circadian entrainment | hsa04713 | Affiliated Target |
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Class: Organismal Systems => Environmental adaptation | Pathway Hierarchy | ||
Insulin secretion | hsa04911 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
Renin secretion | hsa04924 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy |
Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 4.02E-04 |
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Closeness centrality | 1.87E-01 | Radiality | 1.31E+01 | Clustering coefficient | 1.00E-01 |
Neighborhood connectivity | 1.28E+01 | Topological coefficient | 2.22E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Insulin secretion | |||||
Reactome | [+] 3 Reactome Pathways | + | ||||
1 | NGF-independant TRKA activation | |||||
2 | G alpha (s) signalling events | |||||
3 | Glucagon-type ligand receptors | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | SIDS Susceptibility Pathways | |||||
2 | NGF signalling via TRKA from the plasma membrane | |||||
3 | GPCR ligand binding | |||||
4 | GPCR downstream signaling |
References | Top | |||||
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REF 1 | Pituitary adenylate cyclase-activating polypeptides, PACAP-38 and PACAP-27, regulation of sympathetic neuron catecholamine, and neuropeptide Y expr... Ann N Y Acad Sci. 1996 Dec 26;805:204-16; discussion 217-8. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2258). | |||||
REF 3 | ClinicalTrials.gov (NCT02542605) To Evaluate the Blockade of CGRP in Preventing PACAP-38 Induced Migraine-like Attacks With AMG 334 in Migraine Patients. |
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