Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF8319A)

• DOT Name: N-acetylmuramoyl-L-alanine amidase (PGLYRP2)
• Synonyms: EC 3.5.1.28; Peptidoglycan recognition protein 2; Peptidoglycan recognition protein long; PGRP-L
• Gene Name: PGLYRP2
• Related Disease:
  Advanced cancer
  Autism
  Bacteremia
  Bacterial infection
  Fatty liver disease
  Hepatitis
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Parkinson disease
• UniProt ID: PGRP2_HUMAN
• EC Number: 3.5.1.28
• Pfam ID: PF01510
• Sequence:
  MAQGVLWILLGLLLWSDPGTASLPLLMDSVIQALAELEQKVPAAKTRHTASAWLMSAPNS
  GPHNRLYHFLLGAWSLNATELDPCPLSPELLGLTKEVARHDVREGKEYGVVLAPDGSTVA
  VEPLLAGLEAGLQGRRVINLPLDSMAAPWETGDTFPDVVAIAPDVRATSSPGLRDGSPDV
  TTADIGANTPDATKGCPDVQASLPDAKAKSPPTMVDSLLAVTLAGNLGLTFLRGSQTQSH
  PDLGTEGCWDQLSAPRTFTLLDPKASLLTMAFLNGALDGVILGDYLSRTPEPRPSLSHLL
  SQYYGAGVARDPGFRSNFRRQNGAALTSASILAQQVWGTLVLLQRLEPVHLQLQCMSQEQ
  LAQVAANATKEFTEAFLGCPAIHPRCRWGAAPYRGRPKLLQLPLGFLYVHHTYVPAPPCT
  DFTRCAANMRSMQRYHQDTQGWGDIGYSFVVGSDGYVYEGRGWHWVGAHTLGHNSRGFGV
  AIVGNYTAALPTEAALRTVRDTLPSCAVRAGLLRPDYALLGHRQLVRTDCPGDALFDLLR
  TWPHFTATVKPRPARSVSKRSRREPPPRTLPATDLQ
• Function: May play a scavenger role by digesting biologically active peptidoglycan (PGN) into biologically inactive fragments. Has no direct bacteriolytic activity.
• Tissue Specificity: Strongly expressed in liver and fetal liver, and secreted into serum. Expressed to a much lesser extent in transverse colon, lymph nodes, heart, thymus, pancreas, descending colon, stomach and testis. Isoform 2 is not detected in the liver or serum.
• Reactome Pathway: Antimicrobial peptides (R-HSA-6803157)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Bacteremia	DIS6N9RZ	Strong	Biomarker	[3]
Bacterial infection	DIS5QJ9S	Strong	Altered Expression	[4]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[5]
Hepatitis	DISXXX35	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[8]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-acetylmuramoyl-L-alanine amidase (PGLYRP2).	[10]

References

• [1] Tumor-Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma.Hepatology. 2020 May;71(5):1626-1642. doi: 10.1002/hep.30924. Epub 2020 Jan 24.
• [2] The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior.Mol Psychiatry. 2017 Feb;22(2):257-266. doi: 10.1038/mp.2016.182. Epub 2016 Nov 15.
• [3] Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection.Front Microbiol. 2019 Feb 19;10:199. doi: 10.3389/fmicb.2019.00199. eCollection 2019.
• [4] Differential expression of peptidoglycan recognition protein 2 in the skin and liver requires different transcription factors.J Biol Chem. 2006 Jul 28;281(30):20738-20748. doi: 10.1074/jbc.M601017200. Epub 2006 May 19.
• [5] Genome-wide transcriptome analysis identifies novel gene signatures implicated in human chronic liver disease.Am J Physiol Gastrointest Liver Physiol. 2013 Sep 1;305(5):G364-74. doi: 10.1152/ajpgi.00077.2013. Epub 2013 Jun 27.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.