Details of Drug Off-Target (DOT)

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

DOT Name Pepsin A-4 (PGA4)
Synonyms EC 3.4.23.1; Pepsinogen-4
Gene Name PGA4
Related Disease
Craniosynostosis ( )
Nasal polyp ( )
UniProt ID
PEPA4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1FLH; 1PSN; 1PSO; 1QRP; 3UTL
EC Number
3.4.23.1
Pfam ID
PF07966 ; PF00026
Sequence
MKWLLLLGLVALSECIMYKVPLIRKKSLRRTLSERGLLKDFLKKHNLNPARKYFPQWEAP
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

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Craniosynostosis DIS6J405 Strong Biomarker [1]
Nasal polyp DISLP3XE Strong Altered Expression [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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-4 (PGA4). [2]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Pepsin A-4 (PGA4). [3]
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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 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.
3 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.