Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT736H1Q)

• DOT Name: Protein ABHD8 (ABHD8)
• Synonyms: EC 3.-.-.-; Alpha/beta hydrolase domain-containing protein 8; Abhydrolase domain-containing protein 8
• Gene Name: ABHD8
• Related Disease:
  Breast cancer
  Epithelial ovarian cancer
  Systemic lupus erythematosus
• UniProt ID: ABHD8_HUMAN
• EC Number: 3.-.-.-
• Pfam ID: PF00561
• Sequence:
  MLTGVTDGIFCCLLGTPPNAVGPLESVESSDGYTFVEVKPGRVLRVKHAGPAPAAAPPPP
  SSASSDAAQGDLSGLVRCQRRITVYRNGRLLVENLGRAPRADLLHGQNGSGEPPAALEVE
  LADPAGSDGRLAPGSAGSGSGSGSGGRRRRARRPKRTIHIDCEKRITSCKGAQADVVLFF
  IHGVGGSLAIWKEQLDFFVRLGYEVVAPDLAGHGASSAPQVAAAYTFYALAEDMRAIFKR
  YAKKRNVLIGHSYGVSFCTFLAHEYPDLVHKVIMINGGGPTALEPSFCSIFNMPTCVLHC
  LSPCLAWSFLKAGFARQGAKEKQLLKEGNAFNVSSFVLRAMMSGQYWPEGDEVYHAELTV
  PVLLVHGMHDKFVPVEEDQRMAEILLLAFLKLIDEGSHMVMLECPETVNTLLHEFLLWEP
  EPSPKALPEPLPAPPEDKK

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Posttranslational Modification	[2]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[3]

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 Protein ABHD8 (ABHD8).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein ABHD8 (ABHD8).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein ABHD8 (ABHD8).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein ABHD8 (ABHD8).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein ABHD8 (ABHD8).	[8]

References

• [1] A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.Nat Genet. 2010 Oct;42(10):885-92. doi: 10.1038/ng.669. Epub 2010 Sep 19.
• [2] Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk.Cancer Res. 2019 Feb 1;79(3):505-517. doi: 10.1158/0008-5472.CAN-18-2726. Epub 2018 Dec 17.
• [3] Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.Am J Hum Genet. 2013 Jan 10;92(1):41-51. doi: 10.1016/j.ajhg.2012.11.018. Epub 2012 Dec 27.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.