Target Information
Target General Information | Top | |||||
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Target ID |
T16128
(Former ID: TTDI02076)
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Target Name |
Gastrin (GAST)
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Synonyms |
Gastrin6; GAST; G52; G34; G14
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Gene Name |
GAST
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Stomach cancer [ICD-11: 2B72] | |||||
Function |
Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.
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BioChemical Class |
Gastrin cholecystokinin
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UniProt ID | ||||||
Sequence |
MQRLCVYVLIFALALAAFSEASWKPRSQQPDAPLGTGANRDLELPWLEQQGPASHHRRQL
GPQGPPHLVADPSKKQGPWLEEEEEAYGWMDFGRRSAEDEN Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
ADReCS ID | BADD_A01759 | |||||
HIT2.0 ID | T02DKV |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | G17DT | Drug Info | Phase 3 | Gastric adenocarcinoma | [2] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Adenosine-3'-5'-bisphosphate | Ligand Info | |||||
Structure Description | Crystal structure of human tyrosylprotein sulfotransferase-1 complexed with PAP and gastrin peptide | PDB:5WRJ | ||||
Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | No | [3] |
PDB Sequence |
EEEAY
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Click to View More Binding Site Information of This Target with Different Ligands |
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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Gastric acid secretion | hsa04971 | Affiliated Target |
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Class: Organismal Systems => Digestive system | Pathway Hierarchy |
Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 1.56E-01 | Radiality | 1.22E+01 | Clustering coefficient | 1.00E+00 |
Neighborhood connectivity | 4.50E+00 | Topological coefficient | 6.43E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Gastric acid secretion | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | CCKR signaling map ST | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Gastric Acid Production | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | G alpha (q) signalling events | |||||
2 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
2 | Secretion of Hydrochloric Acid in Parietal Cells | |||||
3 | Gastric acid production | |||||
4 | GPCR downstream signaling |
References | Top | |||||
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REF 1 | G17DT: an antigastrin immunogen for the treatment of gastrointestinal malignancy. Expert Opin Biol Ther. 2007 Mar;7(3):397-404. | |||||
REF 2 | ClinicalTrials.gov (NCT02118077) Sequential Trial of G17DT for the Treatment of Advanced Pancreatic Cancer. U.S. National Institutes of Health. | |||||
REF 3 | Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1. Sci Rep. 2017 Aug 18;7(1):8776. |
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