Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPYME8V)

• DOT Name: Cysteine-rich C-terminal protein 1 (CRCT1)
• Synonyms: Protein NICE-1
• Gene Name: CRCT1
• Related Disease:
  Carcinoma of esophagus
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Neoplasm
  Neoplasm of esophagus
  Gingivitis
• UniProt ID: CRCT1_HUMAN
• Pfam ID: PF15845
• Sequence:
  MSSQQSAVSAKGFSKGSSQGPAPCPAPAPTPAPASSSSCCGSGRGCCGDSGCCGSSSTSC
  CCFPRRRRRQRSSGCCCCGGGSQRSQRSNNRSSGCCSGC

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[1]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[1]
Gingivitis	DISC8RMX	moderate	Genetic Variation	[2]

8 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 Cysteine-rich C-terminal protein 1 (CRCT1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[8]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cysteine-rich C-terminal protein 1 (CRCT1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cysteine-rich C-terminal protein 1 (CRCT1).	[10]

References

• [1] CRCT1 regulated by microRNA-520g inhibits proliferation and induces apoptosis in esophageal squamous cell cancer.Tumour Biol. 2016 Jun;37(6):8271-9. doi: 10.1007/s13277-015-4730-2. Epub 2015 Dec 30.
• [2] Salivary exRNA biomarkers to detect gingivitis and monitor disease regression.J Clin Periodontol. 2018 Jul;45(7):806-817. doi: 10.1111/jcpe.12930. Epub 2018 Jun 15.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [8] 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.
• [9] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.