Details of Drug Off-Target (DOT)

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

• DOT Name: Guanine nucleotide-binding protein subunit alpha-15 (GNA15)
• Synonyms: G alpha-15; G-protein subunit alpha-15; Epididymis tissue protein Li 17E; Guanine nucleotide-binding protein subunit alpha-16; G alpha-16; G-protein subunit alpha-16
• Gene Name: GNA15
• Related Disease:
  Acute myelogenous leukaemia
  Acute leukaemia
  Acute lymphocytic leukaemia
  Advanced cancer
  Non-hodgkin lymphoma
  Pancreatic cancer
  Neoplasm
  Neuroendocrine neoplasm
• UniProt ID: GNA15_HUMAN
• Pfam ID: PF00503
• Sequence:
  MARSLTWRCCPWCLTEDEKAAARVDQEINRILLEQKKQDRGELKLLLLGPGESGKSTFIK
  QMRIIHGAGYSEEERKGFRPLVYQNIFVSMRAMIEAMERLQIPFSRPESKHHASLVMSQD
  PYKVTTFEKRYAAAMQWLWRDAGIRACYERRREFHLLDSAVYYLSHLERITEEGYVPTAQ
  DVLRSRMPTTGINEYCFSVQKTNLRIVDVGGQKSERKKWIHCFENVIALIYLASLSEYDQ
  CLEENNQENRMKESLALFGTILELPWFKSTSVILFLNKTDILEEKIPTSHLATYFPSFQG
  PKQDAEAAKRFILDMYTRMYTGCVDGPEGSKKGARSRRLFSHYTCATDTQNIRKVFKDVR
  DSVLARYLDEINLL
• Function: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
• Tissue Specificity: Specifically expressed in hematopoietic cells. Expressed in epididymis (at protein level).
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Relaxin sig.ling pathway (hsa04926)
  Chagas disease (hsa05142)
  Amoebiasis (hsa05146)
• Reactome Pathway:
  G-protein activation (R-HSA-202040)
  Acetylcholine regulates insulin secretion (R-HSA-399997)
  G alpha (q) signalling events (R-HSA-416476)
  ADP signalling through P2Y purinoceptor 1 (R-HSA-418592)
  Thromboxane signalling through TP receptor (R-HSA-428930)
  Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion (R-HSA-434316)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  PLC beta mediated events (R-HSA-112043)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Altered Expression	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]
Neuroendocrine neoplasm	DISNPLOO	Limited	Altered Expression	[5]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Azelaic Acid	DMHVL0J	Approved	Guanine nucleotide-binding protein subunit alpha-15 (GNA15) increases the response to substance of Azelaic Acid.	[13]
geraniol	DMS3CBD	Investigative	Guanine nucleotide-binding protein subunit alpha-15 (GNA15) increases the response to substance of geraniol.	[13]
Octanal	DMTN0OK	Investigative	Guanine nucleotide-binding protein subunit alpha-15 (GNA15) increases the response to substance of Octanal.	[13]
Caprylic acid	DMLGS82	Investigative	Guanine nucleotide-binding protein subunit alpha-15 (GNA15) increases the response to substance of Caprylic acid.	[13]

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 Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Guanine nucleotide-binding protein subunit alpha-15 (GNA15).	[9]

References

• [1] Gene expression profiling in the leukemic stem cell-enriched CD34+ fraction identifies target genes that predict prognosis in normal karyotype AML.Leukemia. 2011 Dec;25(12):1825-33. doi: 10.1038/leu.2011.172. Epub 2011 Jul 15.
• [2] Expression of G alpha 16, a G-protein alpha subunit specific for hematopoiesis in acute leukemia.Leukemia. 1996 Jul;10(7):1117-21.
• [3] G protein subunit G alpha 16 expression is restricted to progenitor B cells during human B-cell differentiation.Blood. 1995 Apr 1;85(7):1836-42.
• [4] Ectopic expression of the heterotrimeric G15 protein in pancreatic carcinoma and its potential in cancer signal transduction.Cell Signal. 2013 Mar;25(3):651-9. doi: 10.1016/j.cellsig.2012.11.018. Epub 2012 Nov 29.
• [5] GNA15 expression in small intestinal neuroendocrine neoplasia: functional and signalling pathway analyses.Cell Signal. 2015 May;27(5):899-907. doi: 10.1016/j.cellsig.2015.02.001. Epub 2015 Feb 17.
• [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] 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.
• [8] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [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] 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.
• [13] Identification of specific ligands for orphan olfactory receptors. G protein-dependent agonism and antagonism of odorants. J Biol Chem. 2005 Mar 25;280(12):11807-15. doi: 10.1074/jbc.M411508200. Epub 2004 Dec 14.