General Information of Drug Off-Target (DOT) (ID: OT9YHSF1)

DOT Name Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8)
Synonyms Gamma-9
Gene Name GNG8
Related Disease
Mycosis fungoides ( )
Primary cutaneous T-cell lymphoma ( )
T-cell lymphoma ( )
UniProt ID
GBG8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00631
Sequence
MSNNMAKIAEARKTVEQLKLEVNIDRMKVSQAAAELLAFCETHAKDDPLVTPVPAAENPF
RDKRLFCVLL
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
Mycosis fungoides DIS62RB8 Limited Genetic Variation [1]
Primary cutaneous T-cell lymphoma DIS35WVW Limited Genetic Variation [1]
T-cell lymphoma DISSXRTQ Limited Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8). [6]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol affects the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8). [3]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8). [4]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 (GNG8). [7]
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References

1 Immunophenotyping and gene rearrangement analysis provide additional criteria to differentiate between cutaneous T-cell lymphomas and pseudo-T-cell lymphomas.Am J Pathol. 1997 Jun;150(6):1941-9.
2 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.
3 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.
4 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.
5 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
6 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.
7 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.