Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8EHCKQ)

• DOT Name: Pepsin A-3 (PGA3)
• Synonyms: EC 3.4.23.1; Pepsinogen-3
• Gene Name: PGA3
• Related Disease:
  Craniosynostosis
  Gastric cancer
  Nasal polyp
  Stomach cancer
  Gastric neoplasm
• UniProt ID: PEPA3_HUMAN
• EC Number: 3.4.23.1
• Pfam ID: PF07966 ; PF00026
• Sequence:
  MKWLLLLGLVALSECIMYKVPLIRKKSLRRTLSERGLLKDFLKKHNLNPARKYFPQWKAP
  TLVDEQPLENYLDMEYFGTIGIGTPAQDFTVVFDTGSSNLWVPSVYCSSLACTNHNRFNP
  EDSSTYQSTSETVSITYGTGSMTGILGYDTVQVGGISDTNQIFGLSETEPGSFLYYAPFD
  GILGLAYPSISSSGATPVFDNIWNQGLVSQDLFSVYLSADDQSGSVVIFGGIDSSYYTGS
  LNWVPVTVEGYWQITVDSITMNGEAIACAEGCQAIVDTGTSLLTGPTSPIANIQSDIGAS
  ENSDGDMVVSCSAISSLPDIVFTINGVQYPVPPSAYILQSEGSCISGFQGMNLPTESGEL
  WILGDVFIRQYFTVFDRANNQVGLAPVA
• Function: Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway: Surfactant metabolism (R-HSA-5683826)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniosynostosis	DIS6J405	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[2]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[2]
Gastric neoplasm	DISOKN4Y	Disputed	Altered Expression	[3]

1 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 Pepsin A-3 (PGA3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Pepsin A-3 (PGA3).	[5]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Pepsin A-3 (PGA3).	[6]

References

• [1] Effects of pepsin A on heat shock protein 70 response in laryngopharyngeal reflux patients with chronic rhinosinusitis.Acta Otolaryngol. 2017 Dec;137(12):1253-1259. doi: 10.1080/00016489.2017.1360515. Epub 2017 Aug 8.
• [2] Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese.Carcinogenesis. 2013 Jul;34(7):1450-7. doi: 10.1093/carcin/bgt079. Epub 2013 Mar 1.
• [3] Histologic and serum risk markers for noncardia early gastric cancer.Int J Cancer. 2005 Jun 20;115(3):463-9. doi: 10.1002/ijc.20852.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.