Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI115BR)

• DOT Name: Peptidoglycan recognition protein 4 (PGLYRP4)
• Synonyms: Peptidoglycan recognition protein I-beta; PGLYRPIbeta; PGRP-I-beta; Peptidoglycan recognition protein intermediate beta
• Gene Name: PGLYRP4
• Related Disease:
  Crohn disease
  Psoriasis
  Bacteremia
  Parkinson disease
  Pneumonia
  Streptococcal pneumonia
• UniProt ID: PGRP4_HUMAN
• PDB ID: 2EAV; 2EAX
• Pfam ID: PF01510
• Sequence:
  MLPWLLVFSALGIQAWGDSSWNKTQAKQVSEGLQYLFENISQLTEKGLPTDVSTTVSRKA
  WGAEAVGCSIQLTTPVNVLVIHHVPGLECHDQTVCSQRLRELQAHHVHNNSGCDVAYNFL
  VGDDGRVYEGVGWNIQGVHTQGYNNISLGFAFFGTKKGHSPSPAALSAMENLITYAVQKG
  HLSSSYVQPLLGKGENCLAPRQKTSLKKACPGVVPRSVWGARETHCPRMTLPAKYGIIIH
  TAGRTCNISDECRLLVRDIQSFYIDRLKSCDIGYNFLVGQDGAIYEGVGWNVQGSSTPGY
  DDIALGITFMGTFTGIPPNAAALEAAQDLIQCAMVKGYLTPNYLLVGHSDVARTLSPGQA
  LYNIISTWPHFKH
• 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, mucous cells in the submandibular salivary gland, mucous cells in the throat, ciliary body epithelial cells of the eye, small intestine, colon, stomach and in mature epithelial cells of the tongue (at protein level). High expression in skin and esophagus. Expressed also to a much lesser extent in the tonsils and thymus.
• 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
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[1]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[2]
Bacteremia	DIS6N9RZ	Limited	Biomarker	[3]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[4]
Pneumonia	DIS8EF3M	Limited	Biomarker	[3]
Streptococcal pneumonia	DIS2EKMJ	Limited	Biomarker	[3]

4 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 Peptidoglycan recognition protein 4 (PGLYRP4).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Peptidoglycan recognition protein 4 (PGLYRP4).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Peptidoglycan recognition protein 4 (PGLYRP4).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Peptidoglycan recognition protein 4 (PGLYRP4).	[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 4 (PGLYRP4).	[8]

References

• [1] 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.
• [2] 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.
• [3] Peptidoglycan Recognition Protein 4 Limits Bacterial Clearance and Inflammation in Lungs by Control of the Gut Microbiota.Front Immunol. 2019 Sep 20;10:2106. doi: 10.3389/fimmu.2019.02106. eCollection 2019.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [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.