Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFOQY1M)

• DOT Name: Gamma-tubulin complex component 3
• Synonyms: GCP-3; hGCP3; Gamma-ring complex protein 104 kDa; h104p; hGrip104; Spindle pole body protein Spc98 homolog; hSpc98
• Gene Name: TUBGCP3
• UniProt ID: GCP3_HUMAN
• PDB ID: 6V6B; 6V6S; 6X0U; 7AS4; 7QJ0; 7QJ1; 7QJ2; 7QJ3; 7QJ4; 7QJ5; 7QJ6; 7QJ7; 7QJ8; 7QJ9; 7QJA; 7QJB; 7QJC; 7QJD
• Pfam ID: PF04130 ; PF17681
• Sequence:
  MATPDQKSPNVLLQNLCCRILGRSEADVAQQFQYAVRVIGSNFAPTVERDEFLVAEKIKK
  ELIRQRREADAALFSELHRKLHSQGVLKNKWSILYLLLSLSEDPRRQPSKVSSYATLFAQ
  ALPRDAHSTPYYYARPQTLPLSYQDRSAQSAQSSGSVGSSGISSIGLCALSGPAPAPQSL
  LPGQSNQAPGVGDCLRQQLGSRLAWTLTANQPSSQATTSKGVPSAVSRNMTRSRREGDTG
  GTMEITEAALVRDILYVFQGIDGKNIKMNNTENCYKVEGKANLSRSLRDTAVRLSELGWL
  HNKIRRYTDQRSLDRSFGLVGQSFCAALHQELREYYRLLSVLHSQLQLEDDQGVNLGLES
  SLTLRRLLVWTYDPKIRLKTLAALVDHCQGRKGGELASAVHAYTKTGDPYMRSLVQHILS
  LVSHPVLSFLYRWIYDGELEDTYHEFFVASDPTVKTDRLWHDKYTLRKSMIPSFMTMDQS
  RKVLLIGKSINFLHQVCHDQTPTTKMIAVTKSAESPQDAADLFTDLENAFQGKIDAAYFE
  TSKYLLDVLNKKYSLLDHMQAMRRYLLLGQGDFIRHLMDLLKPELVRPATTLYQHNLTGI
  LETAVRATNAQFDSPEILRRLDVRLLEVSPGDTGWDVFSLDYHVDGPIATVFTRECMSHY
  LRVFNFLWRAKRMEYILTDIRKGHMCNAKLLRNMPEFSGVLHQCHILASEMVHFIHQMQY
  YITFEVLECSWDELWNKVQQAQDLDHIIAAHEVFLDTIISRCLLDSDSRALLNQLRAVFD
  QIIELQNAQDAIYRAALEELQRRLQFEEKKKQREIEGQWGVTAAEEEEENKRIGEFKESI
  PKMCSQLRILTHFYQGIVQQFLVLLTTSSDESLRFLSFRLDFNEHYKAREPRLRVSLGTR
  GRRSSHT
• Function: Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Menadione	DMSJDTY	Approved	Gamma-tubulin complex component 3 increases the Adverse drug reaction ADR of Menadione.	[13]
Topotecan	DMP6G8T	Approved	Gamma-tubulin complex component 3 affects the response to substance of Topotecan.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Gamma-tubulin complex component 3.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Gamma-tubulin complex component 3.	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Gamma-tubulin complex component 3.	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gamma-tubulin complex component 3.	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Gamma-tubulin complex component 3.	[6]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Gamma-tubulin complex component 3.	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Gamma-tubulin complex component 3.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Gamma-tubulin complex component 3.	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Gamma-tubulin complex component 3.	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Gamma-tubulin complex component 3.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Gamma-tubulin complex component 3.	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Gamma-tubulin complex component 3.	[10]

References

• [1] 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.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] 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.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [14] 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.