Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQT4TKR)

• DOT Name: Carbohydrate sulfotransferase 8 (CHST8)
• Synonyms: EC 2.8.2.-; GalNAc-4-O-sulfotransferase 1; GalNAc-4-ST1; GalNAc4ST-1; N-acetylgalactosamine-4-O-sulfotransferase 1
• Gene Name: CHST8
• Related Disease:
  Peeling skin syndrome 1
  Peeling skin syndrome 6
  Potocki-Shaffer syndrome
  Systemic sclerosis
  Peeling skin syndrome type A
  Asthma
  Atopic dermatitis
  Psoriasis
• UniProt ID: CHST8_HUMAN
• EC Number: 2.8.2.-
• Pfam ID: PF03567
• Sequence:
  MTLRPGTMRLACMFSSILLFGAAGLLLFISLQDPTELAPQQVPGIKFNIRPRQPHHDLPP
  GGSQDGDLKEPTERVTRDLSSGAPRGRNLPAPDQPQPPLQRGTRLRLRQRRRRLLIKKMP
  AAATIPANSSDAPFIRPGPGTLDGRWVSLHRSQQERKRVMQEACAKYRASSSRRAVTPRH
  VSRIFVEDRHRVLYCEVPKAGCSNWKRVLMVLAGLASSTADIQHNTVHYGSALKRLDTFD
  RQGILHRLSTYTKMLFVREPFERLVSAFRDKFEHPNSYYHPVFGKAILARYRANASREAL
  RTGSGVRFPEFVQYLLDVHRPVGMDIHWDHVSRLCSPCLIDYDFVGKFESMEDDANFFLS
  LIRAPRNLTFPRFKDRHSQEARTTARIAHQYFAQLSALQRQRTYDFYYMDYLMFNYSKPF
  ADLY
• Function: Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Required for biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Only active against terminal GalNAcbeta1,GalNAcbeta. Not active toward chondroitin.
• Tissue Specificity: Predominantly expressed in pituitary gland. In brain, it is expressed in pituitary gland, cerebellum, medulla oblongata, pons, thalamus and spinal cord. Expressed in the epidermis. Expressed at lower level in lung, spleen, adrenal gland, placenta, prostate, testis, mammary gland and trachea.
• KEGG Pathway:
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Reactions specific to the complex N-glycan synthesis pathway (R-HSA-975578)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peeling skin syndrome 1	DIS35574	Strong	Genetic Variation	[1]
Peeling skin syndrome 6	DIS1A5FE	Strong	GermlineCausalMutation	[2]
Potocki-Shaffer syndrome	DISKGU59	Strong	Genetic Variation	[2]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[2]
Peeling skin syndrome type A	DIS05EXP	Supportive	Autosomal recessive	[2]
Asthma	DISW9QNS	Limited	Biomarker	[3]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[4]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[4]

3 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 Carbohydrate sulfotransferase 8 (CHST8).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carbohydrate sulfotransferase 8 (CHST8).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Carbohydrate sulfotransferase 8 (CHST8).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carbohydrate sulfotransferase 8 (CHST8).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carbohydrate sulfotransferase 8 (CHST8).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Carbohydrate sulfotransferase 8 (CHST8).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Carbohydrate sulfotransferase 8 (CHST8).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Carbohydrate sulfotransferase 8 (CHST8).	[10]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Carbohydrate sulfotransferase 8 (CHST8).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Carbohydrate sulfotransferase 8 (CHST8).	[14]

References

• [1] The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim.Glycobiology. 2017 May 1;27(5):450-456. doi: 10.1093/glycob/cwx018.
• [2] Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome. Genomics. 2012 Apr;99(4):202-8. doi: 10.1016/j.ygeno.2012.01.005. Epub 2012 Jan 25.
• [3] Analyses of shared genetic factors between asthma and obesity in children.J Allergy Clin Immunol. 2010 Sep;126(3):631-7.e1-8. doi: 10.1016/j.jaci.2010.06.030.
• [4] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] 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.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] 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.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.