Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1KHPKJ)

DOT Name	Deaminated glutathione amidase (NIT1)
Synonyms	dGSH amidase; EC 3.5.1.128; Nitrilase homolog 1
Gene Name	NIT1
Related Disease	Advanced cancer ( ) Colorectal carcinoma ( ) Hyperinsulinemia ( ) Insulinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Lung neoplasm ( ) Neoplasm ( ) Non-small-cell lung cancer ( )
UniProt ID	NIT1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.5.1.128
Pfam ID	PF00795
Sequence	MLGFITRPPHRFLSLLCPGLRIPQLSVLCAQPRPRAMAISSSSCELPLVAVCQVTSTPDK QQNFKTCAELVREAARLGACLAFLPEAFDFIARDPAETLHLSEPLGGKLLEEYTQLAREC GLWLSLGGFHERGQDWEQTQKIYNCHVLLNSKGAVVATYRKTHLCDVEIPGQGPMCESNS TMPGPSLESPVSTPAGKIGLAVCYDMRFPELSLALAQAGAEILTYPSAFGSITGPAHWEV LLRARAIETQCYVVAAAQCGRHHEKRASYGHSMVVDPWGTVVARCSEGPGLCLARIDLNY LRQLRRHLPVFQHRRPDLYGNLGHPLS
Function	Catalyzes the hydrolysis of the amide bond in N-(4-oxoglutarate)-L-cysteinylglycine (deaminated glutathione), a metabolite repair reaction to dispose of the harmful deaminated glutathione. Plays a role in cell growth and apoptosis: loss of expression promotes cell growth, resistance to DNA damage stress and increased incidence to NMBA-induced tumors. Has tumor suppressor properties that enhances the apoptotic responsiveness in cancer cells; this effect is additive to the tumor suppressor activity of FHIT. It is also a negative regulator of primary T-cells.
Tissue Specificity	Detected in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[3]
Insulinoma	DISIU1JS	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Lung neoplasm	DISVARNB	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[5]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

7 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 Deaminated glutathione amidase (NIT1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Deaminated glutathione amidase (NIT1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Deaminated glutathione amidase (NIT1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Deaminated glutathione amidase (NIT1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deaminated glutathione amidase (NIT1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Deaminated glutathione amidase (NIT1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Deaminated glutathione amidase (NIT1).	[12]
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References

1	Biological functions of mammalian Nit1, the counterpart of the invertebrate NitFhit Rosetta stone protein, a possible tumor suppressor.J Biol Chem. 2006 Sep 22;281(38):28244-53. doi: 10.1074/jbc.M603590200. Epub 2006 Jul 24.
2	NIT1 suppresses tumour proliferation by activating the TGF1-Smad2/3 signalling pathway in colorectal cancer.Cell Death Dis. 2018 Feb 15;9(3):263. doi: 10.1038/s41419-018-0333-3.
3	Delivery of two-step transcription amplification exendin-4 plasmid system with arginine-grafted bioreducible polymer in type 2 diabetes animal model.J Control Release. 2012 Aug 20;162(1):9-18. doi: 10.1016/j.jconrel.2012.06.010. Epub 2012 Jun 15.
4	Danzhi Jiangtang Capsule Mediates NIT-1 Insulinoma Cell Proliferation and Apoptosis by GLP-1/Akt Signaling Pathway.Evid Based Complement Alternat Med. 2019 Jul 29;2019:5356825. doi: 10.1155/2019/5356825. eCollection 2019.
5	Nitrilase 1 modulates lung tumor progression in vitro and in vivo.Oncotarget. 2016 Apr 19;7(16):21381-92. doi: 10.18632/oncotarget.7820.
6	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.
7	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.
8	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9	Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
10	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
11	Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
12	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.