Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JPRCQ)

• DOT Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2)
• Synonyms: G protein subunit beta-2; Transducin beta chain 2
• Gene Name: GNB2
• Related Disease:
  Atrioventricular block
  Neoplasm
  Neurodevelopmental disorder with hypotonia and dysmorphic facies
  Prostate cancer
  Prostate carcinoma
  Sinoatrial node disorder
  leukaemia
  Leukemia
  Neuroblastoma
  Sick sinus syndrome 4
• UniProt ID: GBB2_HUMAN
• Pfam ID: PF00400
• Sequence:
  MSELEQLRQEAEQLRNQIRDARKACGDSTLTQITAGLDPVGRIQMRTRRTLRGHLAKIYA
  MHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNFVACGGLDNI
  CSIYSLKTREGNVRVSRELPGHTGYLSCCRFLDDNQIITSSGDTTCALWDIETGQQTVGF
  AGHSGDVMSLSLAPDGRTFVSGACDASIKLWDVRDSMCRQTFIGHESDINAVAFFPNGYA
  FTTGSDDATCRLFDLRADQELLMYSHDNIICGITSVAFSRSGRLLLAGYDDFNCNIWDAM
  KGDRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN
• 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.
• Tissue Specificity: Expressed in all cardiac subcompartments and in the brain, with highest levels in the atrioventricular node and brain.
• 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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrioventricular block	DIS8YLE6	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Neurodevelopmental disorder with hypotonia and dysmorphic facies	DIS96IY2	Strong	Autosomal dominant	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Sinoatrial node disorder	DISYJI6J	Strong	Genetic Variation	[1]
leukaemia	DISS7D1V	Limited	Genetic Variation	[4]
Leukemia	DISNAKFL	Limited	Genetic Variation	[4]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[5]
Sick sinus syndrome 4	DISWL12P	Limited	Unknown	[6]

13 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 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[14]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[15]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[18]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2).	[11]

References

• [1] Exome reports A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features. Eur J Med Genet. 2020 Apr;63(4):103804. doi: 10.1016/j.ejmg.2019.103804. Epub 2019 Nov 4.
• [2] Mutations in G protein subunits promote transformation and kinase inhibitor resistance. Nat Med. 2015 Jan;21(1):71-5. doi: 10.1038/nm.3751. Epub 2014 Dec 8.
• [3] Identification of potential diagnostic and prognostic biomarkers for prostate cancer.Oncol Lett. 2019 Oct;18(4):4237-4245. doi: 10.3892/ol.2019.10765. Epub 2019 Aug 16.
• [4] Molecular pathogenesis of disease progression in MLL-rearranged AML.Leukemia. 2019 Mar;33(3):612-624. doi: 10.1038/s41375-018-0253-3. Epub 2018 Sep 12.
• [5] Exome sequencing identifies predisposing and fusion gene in ganglioneuroma, ganglioneuroblastoma and neuroblastoma.Math Biosci Eng. 2019 Aug 8;16(6):7217-7229. doi: 10.3934/mbe.2019362.
• [6] A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus Node and Atrioventricular Conduction Dysfunction. Circ Res. 2017 May 12;120(10):e33-e44. doi: 10.1161/CIRCRESAHA.116.310112. Epub 2017 Feb 20.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [12] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [15] 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.
• [16] Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
• [17] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [18] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.