Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5C7PRT)

• DOT Name: Peptidoglycan recognition protein 3 (PGLYRP3)
• Synonyms: Peptidoglycan recognition protein I-alpha; PGLYRPIalpha; PGRP-I-alpha; Peptidoglycan recognition protein intermediate alpha
• Gene Name: PGLYRP3
• Related Disease:
  Colitis
  Crohn disease
  Gastroenteritis
  Psoriasis
  Parkinson disease
  Streptococcal pneumonia
• UniProt ID: PGRP3_HUMAN
• PDB ID: 1SK3; 1SK4; 1TWQ; 2APH
• Pfam ID: PF01510
• Sequence:
  MGTLPWLLAFFILGLQAWDTPTIVSRKEWGARPLACRALLTLPVAYIITDQLPGMQCQQQ
  SVCSQMLRGLQSHSVYTIGWCDVAYNFLVGDDGRVYEGVGWNIQGLHTQGYNNISLGIAF
  FGNKIGSSPSPAALSAAEGLISYAIQKGHLSPRYIQPLLLKEETCLDPQHPVMPRKVCPN
  IIKRSAWEARETHCPKMNLPAKYVIIIHTAGTSCTVSTDCQTVVRNIQSFHMDTRNFCDI
  GYHFLVGQDGGVYEGVGWHIQGSHTYGFNDIALGIAFIGYFVEKPPNAAALEAAQDLIQC
  AVVEGYLTPNYLLMGHSDVVNILSPGQALYNIISTWPHFKH
• Function: Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Binds also to Gram-negative bacteria, and has bacteriostatic activity towards Gram-negative bacteria. Plays a role in innate immunity.
• Tissue Specificity: Detected in skin epidermis, eccrine sweat glands and ducts, ciliary body epithelial cells of the eye, in small intestine, colon, stomach and in mature epithelial cells of the tongue (at protein level). Highly expressed in skin and esophagus, expressed also in tonsils and thymus and to a much lesser extent in the stomach, descending colon, rectum and brain.
• Reactome Pathway: Antimicrobial peptides (R-HSA-6803157)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Strong	Altered Expression	[1]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[2]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[3]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[4]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[5]
Streptococcal pneumonia	DIS2EKMJ	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peptidoglycan recognition protein 3 (PGLYRP3).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Peptidoglycan recognition protein 3 (PGLYRP3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peptidoglycan recognition protein 3 (PGLYRP3).	[8]

References

• [1] PGlyRP3 concerts with PPAR to attenuate DSS-induced colitis in mice.Int Immunopharmacol. 2019 Feb;67:46-53. doi: 10.1016/j.intimp.2018.12.005. Epub 2018 Dec 7.
• [2] Genetic Association of Peptidoglycan Recognition Protein Variants with Inflammatory Bowel Disease.PLoS One. 2013 Jun 19;8(6):e67393. doi: 10.1371/journal.pone.0067393. Print 2013.
• [3] Peptidoglycan recognition protein 3 (PglyRP3) has an anti-inflammatory role in intestinal epithelial cells.Immunobiology. 2012 Apr;217(4):412-9. doi: 10.1016/j.imbio.2011.10.013. Epub 2011 Nov 3.
• [4] Peptidoglycan recognition proteins Pglyrp3 and Pglyrp4 are encoded from the epidermal differentiation complex and are candidate genes for the Psors4 locus on chromosome 1q21.Hum Genet. 2006 Mar;119(1-2):113-25. doi: 10.1007/s00439-005-0115-8. Epub 2005 Dec 17.
• [5] Peptidoglycan recognition protein genes and risk of Parkinson's disease.Mov Disord. 2014 Aug;29(9):1171-80. doi: 10.1002/mds.25895. Epub 2014 May 17.
• [6] Peptidoglycan Recognition Protein 3 Does Not Alter the Outcome of Pneumococcal Pneumonia in Mice.Front Microbiol. 2018 Feb 1;9:103. doi: 10.3389/fmicb.2018.00103. eCollection 2018.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.