Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNJJ5Q1)

• DOT Name: Carbohydrate sulfotransferase 11 (CHST11)
• Synonyms: EC 2.8.2.5; Chondroitin 4-O-sulfotransferase 1; Chondroitin 4-sulfotransferase 1; C4S-1; C4ST-1; C4ST1
• Gene Name: CHST11
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Barrett esophagus
  Breast cancer
  Congenital deformities of limbs
  Costello syndrome
  Hepatocellular carcinoma
  Leukoencephalopathy with vanishing white matter
  Neoplasm
  Osteochondrodysplasia, brachydactyly, and overlapping malformed digits
  Schizophrenia
  Small lymphocytic lymphoma
  Breast carcinoma
  Invasive breast carcinoma
• UniProt ID: CHSTB_HUMAN
• EC Number: 2.8.2.5
• Pfam ID: PF03567
• Sequence:
  MKPALLEVMRMNRICRMVLATCLGSFILVIFYFQSMLHPVMRRNPFGVDICCRKGSRSPL
  QELYNPIQLELSNTAVLHQMRRDQVTDTCRANSATSRKRRVLTPNDLKHLVVDEDHELIY
  CYVPKVACTNWKRLMMVLTGRGKYSDPMEIPANEAHVSANLKTLNQYSIPEINHRLKSYM
  KFLFVREPFERLVSAYRNKFTQKYNISFHKRYGTKIIKRQRKNATQEALRKGDDVKFEEF
  VAYLIDPHTQREEPFNEHWQTVYSLCHPCHIHYDLVGKYETLEEDSNYVLQLAGVGSYLK
  FPTYAKSTRTTDEMTTEFFQNISSEHQTQLYEVYKLDFLMFNYSVPSYLKLE
• Function: Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Can also sulfate Gal residues in desulfated dermatan sulfate. Preferentially sulfates in GlcA->GalNAc unit than in IdoA->GalNAc unit. Does not form 4, 6-di-O-sulfated GalNAc when chondroitin sulfate C is used as an acceptor.
• Tissue Specificity: Widely expressed. Highly expressed in spleen, thymus, bone marrow, peripheral blood leukocytes, lymph node, heart, brain, lung and placenta.
• KEGG Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS10284-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[4]
Costello syndrome	DISXVJH3	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Leukoencephalopathy with vanishing white matter	DIS3J8NN	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Osteochondrodysplasia, brachydactyly, and overlapping malformed digits	DISUW3F5	Strong	Autosomal recessive	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[9]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[10]
Invasive breast carcinoma	DISANYTW	Disputed	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[20]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Carbohydrate sulfotransferase 11 (CHST11).	[21]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[22]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[23]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Carbohydrate sulfotransferase 11 (CHST11).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Carbohydrate sulfotransferase 11 (CHST11).	[27]

References

• [1] Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer.Tumour Biol. 2015 Nov;36(11):9023-30. doi: 10.1007/s13277-015-3652-3. Epub 2015 Jun 18.
• [2] Identification and molecular analysis of glycosaminoglycans in cutaneous lupus erythematosus and dermatomyositis.J Histochem Cytochem. 2011 Mar;59(3):336-45. doi: 10.1369/0022155410398000. Epub 2011 Jan 12.
• [3] Chondroitin sulfate-mediated N-cadherin/-catenin signaling is associated with basal-like breast cancer cell invasion.J Biol Chem. 2018 Jan 12;293(2):444-465. doi: 10.1074/jbc.M117.814509. Epub 2017 Nov 28.
• [4] Homozygous CHST11 mutation in chondrodysplasia, brachydactyly, overriding digits, clino-symphalangism and synpolydactyly.J Med Genet. 2018 Jul;55(7):489-496. doi: 10.1136/jmedgenet-2017-105003. Epub 2018 Mar 7.
• [5] C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome.Eur J Hum Genet. 2012 Aug;20(8):870-7. doi: 10.1038/ejhg.2012.12. Epub 2012 Feb 8.
• [6] CHST11/13 Regulate the Metastasis and Chemosensitivity of Human Hepatocellular Carcinoma Cells Via Mitogen-Activated Protein Kinase Pathway.Dig Dis Sci. 2016 Jul;61(7):1972-85. doi: 10.1007/s10620-016-4114-5. Epub 2016 Mar 18.
• [7] Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32).Oncogene. 2004 Sep 9;23(41):6991-6. doi: 10.1038/sj.onc.1207934.
• [8] Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis. Development. 2005 Sep;132(17):3989-4003. doi: 10.1242/dev.01948. Epub 2005 Aug 3.
• [9] Genome-wide association study identifies five new schizophrenia loci.Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940.
• [10] CHST11 gene expression and DNA methylation in breast cancer.Int J Oncol. 2015 Mar;46(3):1243-51. doi: 10.3892/ijo.2015.2828. Epub 2015 Jan 9.
• [11] Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells.Breast Cancer Res. 2011 Jun 9;13(3):R58. doi: 10.1186/bcr2895.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [16] 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.
• [17] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [18] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [19] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [22] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [23] 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.
• [24] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [25] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [26] 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.
• [27] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.