Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLMP2VY)

• DOT Name: Chondroitin sulfate synthase 2 (CHPF)
• Synonyms: EC 2.4.1.175; EC 2.4.1.226; Chondroitin glucuronyltransferase 2; Chondroitin-polymerizing factor; ChPF; Glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase II; N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase II; N-acetylgalactosaminyltransferase 2
• Gene Name: CHPF
• UniProt ID: CHSS2_HUMAN
• EC Number: 2.4.1.175; 2.4.1.226
• Pfam ID: PF05679
• Sequence:
  MRASLLLSVLRPAGPVAVGISLGFTLSLLSVTWVEEPCGPGPPQPGDSELPPRGNTNAAR
  RPNSVQPGAEREKPGAGEGAGENWEPRVLPYHPAQPGQAAKKAVRTRYISTELGIRQRLL
  VAVLTSQTTLPTLGVAVNRTLGHRLERVVFLTGARGRRAPPGMAVVTLGEERPIGHLHLA
  LRHLLEQHGDDFDWFFLVPDTTYTEAHGLARLTGHLSLASAAHLYLGRPQDFIGGEPTPG
  RYCHGGFGVLLSRMLLQQLRPHLEGCRNDIVSARPDEWLGRCILDATGVGCTGDHEGVHY
  SHLELSPGEPVQEGDPHFRSALTAHPVRDPVHMYQLHKAFARAELERTYQEIQELQWEIQ
  NTSHLAVDGDQAAAWPVGIPAPSRPASRFEVLRWDYFTEQHAFSCADGSPRCPLRGADRA
  DVADVLGTALEELNRRYHPALRLQKQQLVNGYRRFDPARGMEYTLDLQLEALTPQGGRRP
  LTRRVQLLRPLSRVEILPVPYVTEASRLTVLLPLAAAERDLAPGFLEAFATAALEPGDAA
  AALTLLLLYEPRQAQRVAHADVFAPVKAHVAELERRFPGARVPWLSVQTAAPSPLRLMDL
  LSKKHPLDTLFLLAGPDTVLTPDFLNRCRMHAISGWQAFFPMHFQAFHPAVAPPQGPGPP
  ELGRDTGRFDRQAASEACFYNSDYVAARGRLAAASEQEEELLESLDVYELFLHFSSLHVL
  RAVEPALLQRYRAQTCSARLSEDLYHRCLQSVLEGLGSRTQLAMLLFEQEQGNST
• Function: Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Seems to act as a specific activating factor for CHSY1 in chondroitin polymerization ; [Isoform 2]: May facilitate PRKN transport into the mitochondria. In collaboration with PRKN, may enhance cell viability and protect cells from oxidative stress.
• Tissue Specificity: Ubiquitous. Highly expressed in pancreas, ovary, brain, heart, skeletal muscle, colon, kidney, liver, stomach, spleen and placenta.; [Isoform 2]: Expressed in brain, spleen, ovary, testis, lung and peripheral mononuclear cells.; [Isoform 3]: Also ubiquitous.
• KEGG Pathway:
  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS13103-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Chondroitin sulfate synthase 2 (CHPF).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chondroitin sulfate synthase 2 (CHPF).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Chondroitin sulfate synthase 2 (CHPF).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chondroitin sulfate synthase 2 (CHPF).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chondroitin sulfate synthase 2 (CHPF).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Chondroitin sulfate synthase 2 (CHPF).	[15]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [13] 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.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.