Details of Drug Off-Target (DOT)

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

• DOT Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11)
• Synonyms: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
• Gene Name: GNG11
• Related Disease:
  Crohn disease
  Juvenile idiopathic arthritis
  Lung adenocarcinoma
  Ulcerative colitis
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Arrhythmia
• UniProt ID: GBG11_HUMAN
• Pfam ID: PF00631
• Sequence:
  MPALHIEDLPEKEKLKMEVEQLRKEVKLQRQQVSKCSEEIKNYIEERSGEDPLVKGIPED
  KNPFKEKGSCVIS
• 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: Abundantly expressed in all tissues tested except for 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Strong	Biomarker	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Altered Expression	[4]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Biomarker	[4]
Arrhythmia	DISFF2NI	Limited	Genetic Variation	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11) affects the response to substance of Methotrexate.	[25]

1 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 G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[11]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[14]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[16]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[23]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 (GNG11).	[24]

References

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• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium.Oncol Rep. 2014 Mar;31(3):1323-33. doi: 10.3892/or.2013.2937. Epub 2013 Dec 20.
• [4] Identification of new markers discriminating between myeloid and lymphoid acute leukemia.Hematology. 2010 Aug;15(4):193-203. doi: 10.1179/102453310X12647083620769.
• [5] Genetic loci associated with heart rate variability and their effects on cardiac disease risk.Nat Commun. 2017 Jun 14;8:15805. doi: 10.1038/ncomms15805.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [16] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [17] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [18] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [19] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [20] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [21] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [22] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.