Details of Drug Off-Target (DOT)

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

• DOT Name: Gastricsin (PGC)
• Synonyms: EC 3.4.23.3; Pepsinogen C
• Gene Name: PGC
• UniProt ID: PEPC_HUMAN
• PDB ID: 1AVF; 1HTR
• EC Number: 3.4.23.3
• Pfam ID: PF07966 ; PF00026
• Sequence:
  MKWMVVVLVCLQLLEAAVVKVPLKKFKSIRETMKEKGLLGEFLRTHKYDPAWKYRFGDLS
  VTYEPMAYMDAAYFGEISIGTPPQNFLVLFDTGSSNLWVPSVYCQSQACTSHSRFNPSES
  STYSTNGQTFSLQYGSGSLTGFFGYDTLTVQSIQVPNQEFGLSENEPGTNFVYAQFDGIM
  GLAYPALSVDEATTAMQGMVQEGALTSPVFSVYLSNQQGSSGGAVVFGGVDSSLYTGQIY
  WAPVTQELYWQIGIEEFLIGGQASGWCSEGCQAIVDTGTSLLTVPQQYMSALLQATGAQE
  DEYGQFLVNCNSIQNLPSLTFIINGVEFPLPPSSYILSNNGYCTVGVEPTYLSSQNGQPL
  WILGDVFLRSYYSVYDLGNNRVGFATAA
• Function: Hydrolyzes a variety of proteins.

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Gastricsin (PGC).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Gastricsin (PGC).	[8]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Gastricsin (PGC).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Gastricsin (PGC).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Gastricsin (PGC).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Gastricsin (PGC).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Gastricsin (PGC).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Gastricsin (PGC).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Gastricsin (PGC).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Gastricsin (PGC).	[9]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Gastricsin (PGC).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Gastricsin (PGC).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the expression of Gastricsin (PGC).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Gastricsin (PGC).	[11]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Gastricsin (PGC).	[6]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Gastricsin (PGC).	[5]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.