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ATP4A

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Target not currently curated in GtoImmuPdb

Target id: 849

Nomenclature: ATP4A

Family: H+/K+-ATPases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 10 1035 19q13.12 ATP4A ATPase H+/K+ transporting subunit alpha
Mouse 10 1033 7 19.2 cM Atp4a ATPase, H+/K+ exchanging, gastric, alpha polypeptide
Rat 10 1033 1q21 Atp4a ATPase H+/K+ transporting subunit alpha
Previous and Unofficial Names Click here for help
ATP6A | ATPase | ATPase, H+/K+ exchanging, alpha polypeptide | ATPase, H+/K+ exchanging, gastric, alpha polypeptide | ATPase H+/K+ transporting alpha subunit | gastric H,K-ATPase alpha subunit | gastric H,K-ATPase catalytic subunit | gastric H(+)/K(+) ATPase subunit alpha | Hka | H+/K+-ATPase alpha | H(+)-K(+)-ATPase alpha subunit | HKATPC | H+K+-transporting alpha 1 | potassium-transporting ATPase alpha chain 1
Database Links Click here for help
Alphafold P20648 (Hs), Q64436 (Mm), P09626 (Rn)
BRENDA 7.2.2.19
CATH/Gene3D 3.40.1110.10
ChEMBL Target CHEMBL2095173 (Hs), CHEMBL2095199 (Rn)
DrugBank Target P20648 (Hs)
Ensembl Gene ENSG00000105675 (Hs), ENSMUSG00000005553 (Mm), ENSRNOG00000020985 (Rn)
Entrez Gene 495 (Hs), 11944 (Mm), 24216 (Rn)
Human Protein Atlas ENSG00000105675 (Hs)
KEGG Enzyme 7.2.2.19
KEGG Gene hsa:495 (Hs), mmu:11944 (Mm), rno:24216 (Rn)
OMIM 137216 (Hs)
Pharos P20648 (Hs)
UniProtKB P20648 (Hs), Q64436 (Mm), P09626 (Rn)
Wikipedia ATP4A (Hs)
Enzyme Reaction Click here for help
EC Number: 7.2.2.19

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ilaprazole Small molecule or natural product Approved drug Oc Inhibition 8.1 pIC50 4
⤷ pIC50 8.1 (IC50 9x10-9 M) [4]
Description: Measuring inhibition of histamine-induced accumulation of 14C-aminopyrine in rabbit parietal cells.
vonoprazan Small molecule or natural product Approved drug Ligand has a PDB structure Pig Inhibition 7.7 pIC50 1
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [1]
Description: Inhibition of H+/K+-ATPase activity in a gastric mucosal membrane microsomal fraction from pig stomach.
tegoprazan Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 6.3 pIC50 5
⤷ pIC50 6.3 (IC50 5.2x10-7 M) [5]
Description: Inhibition of the H+/K+-ATPase activity of recombinant human enzyme
revaprazan Small molecule or natural product Approved drug Pig Inhibition 5.6 – 6.5 pIC50 6-7
⤷ pIC50 6.5 (IC50 3.5x10-7 M) [7]
Description: Inhibitory activity against H+/K+ ATPase isolated from hog gastric mucosa
pIC50 5.6 (IC50 2.3x10-6 M) [6]
omeprazole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition - -
⤷
esomeprazole Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
View species-specific inhibitor tables
Inhibitor Comments
The mechanism of interaction of lansoprazole with the porcine gastric proton pump has been reported [2]. It inhibits proton transport in gastric glands of isolated rabbit stomach with an IC50 of approximately 400 nM [3].

References

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1. Arikawa Y, Nishida H, Kurasawa O, Hasuoka A, Hirase K, Inatomi N, Hori Y, Matsukawa J, Imanishi A, Kondo M et al.. (2012) Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate (TAK-438) as a potassium-competitive acid blocker (P-CAB). J Med Chem, 55 (9): 4446-56. [PMID:22512618]

2. Besancon M, Simon A, Sachs G, Shin JM. (1997) Sites of reaction of the gastric H,K-ATPase with extracytoplasmic thiol reagents. J Biol Chem, 272 (36): 22438-46. [PMID:9278394]

3. Kohl B, Sturm E, Senn-Bilfinger J, Simon WA, Krüger U, Schaefer H, Rainer G, Figala V, Klemm K. (1992) (H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate. J Med Chem, 35 (6): 1049-57. [PMID:1313110]

4. Kwon D, Chae JB, Park CW, Kim YS, Lee SM, Kim EJ, Huh IH, Kim DY, Cho KD. (2001) Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo. Arzneimittelforschung, 51 (3): 204-13. [PMID:11304936]

5. Takahashi N, Take Y. (2018) Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility. J Pharmacol Exp Ther, 364 (2): 275-286. [PMID:29180359]

6. Tanaka S, Morita M, Yamagishi T, Madapally HV, Hayashida K, Khandelia H, Gerle C, Shigematsu H, Oshima A, Abe K. (2022) Structural Basis for Binding of Potassium-Competitive Acid Blockers to the Gastric Proton Pump. J Med Chem, 65 (11): 7843-7853. [PMID:35604136]

7. Yoon YA, Park CS, Cha MH, Choi H, Sim JY, Kim JG. (2010) Novel pyrimidines as acid pump antagonists (APAs). Bioorg Med Chem Lett, 20 (19): 5735-8. [PMID:20810280]

How to cite this page

H+/K+-ATPases: ATP4A. Last modified on 24/05/2022. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=849.