General Information of Drug Off-Target (DOT) (ID: OTBT1O58)

DOT Name V-type proton ATPase subunit G 1 (ATP6V1G1)
Synonyms V-ATPase subunit G 1; V-ATPase 13 kDa subunit 1; Vacuolar proton pump subunit G 1; Vacuolar proton pump subunit M16
Gene Name ATP6V1G1
Related Disease
Osteoporosis ( )
Rheumatoid arthritis ( )
UniProt ID
VATG1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6WLZ; 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
Pfam ID
PF03179
Sequence
MASQSQGIQQLLQAEKRAAEKVSEARKRKNRRLKQAKEEAQAEIEQYRLQREKEFKAKEA
AALGSRGSCSTEVEKETQEKMTILQTYFRQNRDEVLDNLLAFVCDIRPEIHENYRING
Function
Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation.
Tissue Specificity Kidney; localizes to early distal nephron, encompassing thick ascending limbs and distal convoluted tubules (at protein level) . Ubiquitous .
KEGG Pathway
Oxidative phosphorylation (hsa00190 )
Metabolic pathways (hsa01100 )
Phagosome (hsa04145 )
mTOR sig.ling pathway (hsa04150 )
Sy.ptic vesicle cycle (hsa04721 )
Collecting duct acid secretion (hsa04966 )
Vibrio cholerae infection (hsa05110 )
Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120 )
Human papillomavirus infection (hsa05165 )
Rheumatoid arthritis (hsa05323 )
Reactome Pathway
Insulin receptor recycling (R-HSA-77387 )
Transferrin endocytosis and recycling (R-HSA-917977 )
Amino acids regulate mTORC1 (R-HSA-9639288 )
Ion channel transport (R-HSA-983712 )
ROS and RNS production in phagocytes (R-HSA-1222556 )
BioCyc Pathway
MetaCyc:HS06241-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Osteoporosis DISF2JE0 Strong Biomarker [1]
Rheumatoid arthritis DISTSB4J Limited Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [8]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [10]
Milchsaure DM462BT Investigative Milchsaure increases the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [11]
chloropicrin DMSGBQA Investigative chloropicrin affects the expression of V-type proton ATPase subunit G 1 (ATP6V1G1). [12]
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⏷ Show the Full List of 10 Drug(s)

References

1 Bivariate Genome-Wide Association Study Implicates ATP6V1G1 as a Novel Pleiotropic Locus Underlying Osteoporosis and Age at Menarche.J Clin Endocrinol Metab. 2015 Nov;100(11):E1457-66. doi: 10.1210/jc.2015-2095. Epub 2015 Aug 27.
2 A second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III region.Genomics. 2001 Feb 1;71(3):263-70. doi: 10.1006/geno.2000.6371.
3 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
5 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
8 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
9 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
10 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
11 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
12 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.