Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6L79OO)

• DOT Name: Gypsy retrotransposon integrase-like protein 1 (GIN1)
• Synonyms: GIN-1; Ty3/Gypsy integrase 1; Zinc finger H2C2 domain-containing protein
• Gene Name: GIN1
• Related Disease:
  Non-insulin dependent diabetes
  T-cell leukaemia
  Rheumatoid arthritis
• UniProt ID: GIN1_HUMAN
• Pfam ID: PF17921 ; PF00665
• Sequence:
  MVRSGKNGDLHLKQIAYYKRTGEYHSTTLPSERSGIRRAAKKFVFKEKKLFYVGKDRKQN
  RLVIVSEEEKKKVLRECHENDSGAHHGISRTLTLVESNYYWTSVTNDVKQWVYACQHCQV
  AKNTVIVAPKQHLLKVENPWSLVTVDLMGPFHTSNRSHVYAIIMTDLFTKWIVILPLCDV
  SASEVSKAIINIFFLYGPPQKIIMDQRDEFIQQINIELYRLFGIKQIVISHTSGTVNPTE
  STPNTIKAFLSKHCADHPNNWDDHLSAVSFAFNVTHLEPTKNTPYFQMFSRNPYMPETSD
  SLHEVDGDNTSMFAKILDAIKEADKIMENKTTSLGQMENNNLDELNKSKIIVKKKPKQLN
  PFHLKVGHEVLRQRKNWWKDGRFQSEWVGPCVIDYITESGCAVLRDNTGVRLKRPIKMSH
  LKPYIRESSEQESLYLLQGSVVADHDYIGLPEIPIGAYQANILVEDATIGIVDNELLTSS
  KDRELLEYRNTKISPLIDDHSSLEKQTFSLLDSSNQVLEYLS
• Tissue Specificity: Widely expressed. Also found in tumors originating from parathyroid gland, colon, stomach, bladder, uterus and prostate.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[1]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[9]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[12]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Gypsy retrotransposon integrase-like protein 1 (GIN1).	[13]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia.Oncogene. 1991 Nov;6(11):2041-7.
• [3] High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.Nat Genet. 2012 Dec;44(12):1336-40. doi: 10.1038/ng.2462. Epub 2012 Nov 11.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.