Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXDD006)

• DOT Name: Protein NKG7 (NKG7)
• Synonyms: G-CSF-induced gene 1 protein; GIG-1 protein; Granule membrane protein of 17 kDa; GMP-17; Natural killer cell protein 7; p15-TIA-1
• Gene Name: NKG7
• Related Disease:
  Acute myelogenous leukaemia
  Mycosis fungoides
  Sezary syndrome
• UniProt ID: NKG7_HUMAN
• Pfam ID: PF00822
• Sequence:
  MELCRSLALLGGSLGLMFCLIALSTDFWFEAVGPTHSAHSGLWPTGHGDIISGYIHVTQT
  FSIMAVLWALVSVSFLVLSCFPSLFPPGHGPLVSTTAAFAAAISMVVAMAVYTSERWDQP
  PHPQIQTFFSWSFYLGWVSAILLLCTGALSLGAHCGGPRPGYETL
• Function: Regulates cytotoxic granule exocytosis in effector lymphocytes, thus acting as a critical mediator of inflammation in a broad range of infectious and non-infectious diseases. Essential for cytotoxic degranulation of natural killer (NK) cells and CD8(+) T-cells and for the activation of CD4(+) T-cells following infection. Plays a critical role in CD8(+) T-cell and NK cell-mediated cytolysis of target cells and contributes to the cytolytic activity via the perforin/granzyme pathway by enhancing exocytosis of LAMP1-carrying lytic granules. Contributes to NK cell-mediated control of cancer metastasis.
• Tissue Specificity: Expressed in activated T-cells, in kidney, liver, lung and pancreas. Not expressed in brain, heart, or skeletal muscle. Expressed at high levels in TCR gamma delta-expressing CTL clones, and in some TCR alpha beta-expressing CTL clones (both CD4+ and CD8+), but is not expressed in other TCR alpha beta-expressing CTL clones and in cell lines representing B-cells, monocytes, and myeloid cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[1]
Mycosis fungoides	DIS62RB8	Limited	Altered Expression	[2]
Sezary syndrome	DISFMTC7	Limited	Altered Expression	[2]

2 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 NKG7 (NKG7).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein NKG7 (NKG7).	[10]

9 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 Protein NKG7 (NKG7).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein NKG7 (NKG7).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein NKG7 (NKG7).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein NKG7 (NKG7).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein NKG7 (NKG7).	[8]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Protein NKG7 (NKG7).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein NKG7 (NKG7).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein NKG7 (NKG7).	[11]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Protein NKG7 (NKG7).	[12]

References

• [1] Significant expression of G-CSF-induced gene-1 (GIG-1) protein in myeloid cells and NK cells.J Leukoc Biol. 1999 Jan;65(1):109-16. doi: 10.1002/jlb.65.1.109.
• [2] Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma.Clin Cancer Res. 2006 Aug 15;12(16):4812-21. doi: 10.1158/1078-0432.CCR-06-0532.
• [3] 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.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [8] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [9] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.