Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2SH7HJ)

• DOT Name: Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2)
• Synonyms: EC 2.4.1.174; Chondroitin beta-1,4-N-acetylgalactosaminyltransferase 2; Beta4GalNAcT-2; GalNAcT-2
• Gene Name: CSGALNACT2
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Multiple sclerosis
  Hirschsprung disease
• UniProt ID: CGAT2_HUMAN
• EC Number: 2.4.1.174
• Pfam ID: PF05679
• Sequence:
  MPRRGLILHTRTHWLLLGLALLCSLVLFMYLLECAPQTDGNASLPGVVGENYGKEYYQAL
  LQEQEEHYQTRATSLKRQIAQLKQELQEMSEKMRSLQERRNVGANGIGYQSNKEQAPSDL
  LEFLHSQIDKAEVSIGAKLPSEYGVIPFESFTLMKVFQLEMGLTRHPEEKPVRKDKRDEL
  VEVIEAGLEVINNPDEDDEQEDEEGPLGEKLIFNENDFVEGYYRTERDKGTQYELFFKKA
  DLTEYRHVTLFRPFGPLMKVKSEMIDITRSIINIIVPLAERTEAFVQFMQNFRDVCIHQD
  KKIHLTVVYFGKEGLSKVKSILESVTSESNFHNYTLVSLNEEFNRGRGLNVGARAWDKGE
  VLMFFCDVDIYFSAEFLNSCRLNAEPGKKVFYPVVFSLYNPAIVYANQEVPPPVEQQLVH
  KKDSGFWRDFGFGMTCQYRSDFLTIGGFDMEVKGWGGEDVHLYRKYLHGDLIVIRTPVPG
  LFHLWHEKRCADELTPEQYRMCIQSKAMNEASHSHLGMLVFREEIETHLHKQAYRTNSEA
  VG
• Function: Transfers 1,4-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of glucuronic acid (GlcUA). Required for addition of the first GalNAc to the core tetrasaccharide linker and for elongation of chondroitin chains.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS10013-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[1]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[1]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[2]
Hirschsprung disease	DISUUSM1	moderate	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[9]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2).	[15]

References

• [1] Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration.Biochem Biophys Res Commun. 2019 Jan 29;509(1):89-95. doi: 10.1016/j.bbrc.2018.12.068. Epub 2018 Dec 20.
• [2] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.Nat Genet. 2013 Nov;45(11):1353-60. doi: 10.1038/ng.2770. Epub 2013 Sep 29.
• [3] A genome-wide association study identifies potential susceptibility loci for Hirschsprung disease.PLoS One. 2014 Oct 13;9(10):e110292. doi: 10.1371/journal.pone.0110292. eCollection 2014.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.