Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD7H0G6)

• DOT Name: Lysozyme C (LYZ)
• Synonyms: EC 3.2.1.17; 1,4-beta-N-acetylmuramidase C
• Gene Name: LYZ
• Related Disease:
  Familial visceral amyloidosis
  ALys amyloidosis
• UniProt ID: LYSC_HUMAN
• PDB ID: 133L ; 134L ; 1B5U ; 1B5V ; 1B5W ; 1B5X ; 1B5Y ; 1B5Z ; 1B7L ; 1B7M ; 1B7N ; 1B7O ; 1B7P ; 1B7Q ; 1B7R ; 1B7S ; 1BB3 ; 1BB4 ; 1BB5 ; 1C43 ; 1C45 ; 1C46 ; 1C7P ; 1CJ6 ; 1CJ7 ; 1CJ8 ; 1CJ9 ; 1CKC ; 1CKD ; 1CKF ; 1CKG ; 1CKH ; 1D6P ; 1D6Q ; 1DI3 ; 1DI4 ; 1DI5 ; 1EQ4 ; 1EQ5 ; 1EQE ; 1GAY ; 1GAZ ; 1GB0 ; 1GB2 ; 1GB3 ; 1GB5 ; 1GB6 ; 1GB7 ; 1GB8 ; 1GB9 ; 1GBO ; 1GBW ; 1GBX ; 1GBY ; 1GBZ ; 1GDW ; 1GDX ; 1GE0 ; 1GE1 ; 1GE2 ; 1GE3 ; 1GE4 ; 1GEV ; 1GEZ ; 1GF0 ; 1GF3 ; 1GF4 ; 1GF5 ; 1GF6 ; 1GF7 ; 1GF8 ; 1GF9 ; 1GFA ; 1GFE ; 1GFG ; 1GFH ; 1GFJ ; 1GFK ; 1GFR ; 1GFT ; 1GFU ; 1GFV ; 1HNL ; 1I1Z ; 1I20 ; 1I22 ; 1INU ; 1IOC ; 1IP1 ; 1IP2 ; 1IP3 ; 1IP4 ; 1IP5 ; 1IP6 ; 1IP7 ; 1IWT ; 1IWU ; 1IWV ; 1IWW ; 1IWX ; 1IWY ; 1IWZ ; 1IX0 ; 1IY3 ; 1IY4 ; 1JKA ; 1JKB ; 1JKC ; 1JKD ; 1JSF ; 1JWR ; 1LAA ; 1LHH ; 1LHI ; 1LHJ ; 1LHK ; 1LHL ; 1LHM ; 1LMT ; 1LOZ ; 1LYY ; 1LZ1 ; 1LZ4 ; 1LZ5 ; 1LZ6 ; 1LZR ; 1LZS ; 1OP9 ; 1OUA ; 1OUB ; 1OUC ; 1OUD ; 1OUE ; 1OUF ; 1OUG ; 1OUH ; 1OUI ; 1OUJ ; 1QSW ; 1RE2 ; 1REM ; 1REX ; 1REY ; 1REZ ; 1TAY ; 1TBY ; 1TCY ; 1TDY ; 1UBZ ; 1W08 ; 1WQM ; 1WQN ; 1WQO ; 1WQP ; 1WQQ ; 1WQR ; 1YAM ; 1YAN ; 1YAO ; 1YAP ; 1YAQ ; 207L ; 208L ; 2BQA ; 2BQB ; 2BQC ; 2BQD ; 2BQE ; 2BQF ; 2BQG ; 2BQH ; 2BQI ; 2BQJ ; 2BQK ; 2BQL ; 2BQM ; 2BQN ; 2BQO ; 2HEA ; 2HEB ; 2HEC ; 2HED ; 2HEE ; 2HEF ; 2LHM ; 2MEA ; 2MEB ; 2MEC ; 2MED ; 2MEE ; 2MEF ; 2MEG ; 2MEH ; 2MEI ; 2NWD ; 2ZIJ ; 2ZIK ; 2ZIL ; 2ZWB ; 3EBA ; 3FE0 ; 3LHM ; 3LN2 ; 4I0C ; 4ML7 ; 4R0P ; 5LSH ; 5LVK ; 6LFH ; 7AP7 ; 7XF6 ; 7XF7 ; 7XF8
• EC Number: 3.2.1.17
• Pfam ID: PF00062
• Sequence:
  MKALIVLGLVLLSVTVQGKVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYNTRA
  TNYNAGDRSTDYGIFQINSRYWCNDGKTPGAVNACHLSCSALLQDNIADAVACAKRVVRD
  PQGIRAWVAWRNRCQNRDVRQYVQGCGV
• Function: Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.
• KEGG Pathway: Salivary secretion (hsa04970)
• Reactome Pathway:
  Antimicrobial peptides (R-HSA-6803157)
  Amyloid fiber formation (R-HSA-977225)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial visceral amyloidosis	DIS7BVSW	Strong	Autosomal dominant	[1]
ALys amyloidosis	DIS4X1TS	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Tobramycin	DMUI0CH	Approved	Lysozyme C (LYZ) increases the Nephropathy toxic ADR of Tobramycin.	[23]
Captopril	DM458UM	Approved	Lysozyme C (LYZ) increases the Leukopenia ADR of Captopril.	[23]

19 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 Lysozyme C (LYZ).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lysozyme C (LYZ).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysozyme C (LYZ).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lysozyme C (LYZ).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lysozyme C (LYZ).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Lysozyme C (LYZ).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Lysozyme C (LYZ).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lysozyme C (LYZ).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Lysozyme C (LYZ).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Lysozyme C (LYZ).	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Lysozyme C (LYZ).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Lysozyme C (LYZ).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Lysozyme C (LYZ).	[16]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Lysozyme C (LYZ).	[16]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Lysozyme C (LYZ).	[17]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Lysozyme C (LYZ).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Lysozyme C (LYZ).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysozyme C (LYZ).	[13]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Lysozyme C (LYZ).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Lysozyme C (LYZ).	[13]

6 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Glibenclamide	DM8JXPZ	Approved	Glibenclamide decreases the secretion of Lysozyme C (LYZ).	[18]
Carbachol	DMX9K8F	Approved	Carbachol affects the secretion of Lysozyme C (LYZ).	[18]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the secretion of Lysozyme C (LYZ).	[18]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the secretion of Lysozyme C (LYZ).	[21]
Heme	DMGC287	Investigative	Heme increases the secretion of Lysozyme C (LYZ).	[22]
EBIO	DMPKI0N	Investigative	EBIO affects the secretion of Lysozyme C (LYZ).	[18]

References

• [1] Mechanistic studies of the folding of human lysozyme and the origin of amyloidogenic behavior in its disease-related variants. Biochemistry. 1999 May 18;38(20):6419-27. doi: 10.1021/bi983037t.
• [2] Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French family. Kidney Int. 2002 Mar;61(3):907-12. doi: 10.1046/j.1523-1755.2002.00205.x.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [12] DNA microarray analysis of changes in gene expression induced by 1,25-dihydroxyvitamin D3 in human promyelocytic leukemia HL-60 cells. Biomed Res. 2006 Jun;27(3):99-109. doi: 10.2220/biomedres.27.99.
• [13] Inhibitors of DNA methylation and histone deacetylation independently relieve AML1/ETO-mediated lysozyme repression. J Leukoc Biol. 2006 Dec;80(6):1462-72. doi: 10.1189/jlb.0106005. Epub 2006 Sep 25.
• [14] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [17] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [18] Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells. J Biol Chem. 2004 Sep 10;279(37):38854-60. doi: 10.1074/jbc.M407077200. Epub 2004 Jul 2.
• [19] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [20] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [21] Regulation of apical surface fluid and protein secretion in human airway epithelial cell line Calu-3. Biochem Biophys Res Commun. 2004 Jul 9;319(4):1132-7. doi: 10.1016/j.bbrc.2004.05.101.
• [22] Role of 15-hydroxyeicosatetraenoic acid in hemozoin-induced lysozyme release from human adherent monocytes. Biofactors. 2013 May-Jun;39(3):304-14. doi: 10.1002/biof.1071. Epub 2013 Jan 28.
• [23] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.