Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5LR7MB)

• DOT Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5)
• Synonyms: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
• Gene Name: GNG5
• Related Disease:
  Essential hypertension
  Prostate cancer
  Prostate neoplasm
• UniProt ID: GBG5_HUMAN
• Pfam ID: PF00631
• Sequence:
  MSGSSSVAAMKKVVQQLRLEAGLNRVKVSQAAADLKQFCLQNAQHDPLLTGVSSSTNPFR
  PQKVCSFL
• Function: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Chemokine sig.ling pathway (hsa04062)
  PI3K-Akt sig.ling pathway (hsa04151)
  Apelin sig.ling pathway (hsa04371)
  Circadian entrainment (hsa04713)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Glutamatergic sy.pse (hsa04724)
  Cholinergic sy.pse (hsa04725)
  Serotonergic sy.pse (hsa04726)
  GABAergic sy.pse (hsa04727)
  Dopaminergic sy.pse (hsa04728)
  Relaxin sig.ling pathway (hsa04926)
  Morphine addiction (hsa05032)
  Alcoholism (hsa05034)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  Glucagon signaling in metabolic regulation (R-HSA-163359)
  G-protein activation (R-HSA-202040)
  Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676)
  ADP signalling through P2Y purinoceptor 12 (R-HSA-392170)
  G beta (R-HSA-392451)
  Prostacyclin signalling through prostacyclin receptor (R-HSA-392851)
  Adrenaline,noradrenaline inhibits insulin secretion (R-HSA-400042)
  Ca2+ pathway (R-HSA-4086398)
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (12/13) signalling events (R-HSA-416482)
  G beta (R-HSA-418217)
  G alpha (s) signalling events (R-HSA-418555)
  ADP signalling through P2Y purinoceptor 1 (R-HSA-418592)
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (z) signalling events (R-HSA-418597)
  Glucagon-type ligand receptors (R-HSA-420092)
  Thromboxane signalling through TP receptor (R-HSA-428930)
  Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Presynaptic function of Kainate receptors (R-HSA-500657)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  G beta (R-HSA-8964315)
  G beta (R-HSA-8964616)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  GPER1 signaling (R-HSA-9634597)
  ADORA2B mediated anti-inflammatory cytokines production (R-HSA-9660821)
  Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits (R-HSA-997272)
  Activation of G protein gated Potassium channels (R-HSA-1296041)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]

5 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 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 (GNG5).	[9]

References

• [1] Association between single nucleotide polymorphisms of the G-protein 5 subunit and the risk of essential hypertension in the population of Poland.Pol Arch Med Wewn. 2015;125(12):903-9. doi: 10.20452/pamw.3207. Epub 2015 Nov 16.
• [2] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] 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.