Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA9KV6C)

• DOT Name: GTP-binding protein 1 (GTPBP1)
• Synonyms: G-protein 1; GP-1; GP1
• Gene Name: GTPBP1
• Related Disease:
  Amyotrophic lateral sclerosis
  Hepatocellular carcinoma
  Thrombophilia
  Autoimmune polyendocrinopathy
  Ebola virus infection
• UniProt ID: GTPB1_HUMAN
• Pfam ID: PF00009 ; PF03144
• Sequence:
  MATERSRSAMDSPVPASMFAPEPSSPGAARAAAAAARLHGGFDSDCSEDGEALNGEPELD
  LTSKLVLVSPTSEQYDSLLRQMWERMDEGCGETIYVIGQGSDGTEYGLSEADMEASYATV
  KSMAEQIEADVILLRERQEAGGRVRDYLVRKRVGDNDFLEVRVAVVGNVDAGKSTLLGVL
  THGELDNGRGFARQKLFRHKHEIESGRTSSVGNDILGFDSEGNVVNKPDSHGGSLEWTKI
  CEKSTKVITFIDLAGHEKYLKTTVFGMTGHLPDFCMLMVGSNAGIVGMTKEHLGLALALN
  VPVFVVVTKIDMCPANILQETLKLLQRLLKSPGCRKIPVLVQSKDDVIVTASNFSSERMC
  PIFQISNVTGENLDLLKMFLNLLSPRTSYREEEPAEFQIDDTYSVPGVGTVVSGTTLRGL
  IKLNDTLLLGPDPLGNFLSIAVKSIHRKRMPVKEVRGGQTASFALKKIKRSSIRKGMVMV
  SPRLNPQASWEFEAEILVLHHPTTISPRYQAMVHCGSIRQTATILSMDKDCLRTGDKATV
  HFRFIKTPEYLHIDQRLVFREGRTKAVGTITKLLQTTNNSPMNSKPQQIKMQSTKKGPLT
  KRDEGGPSGGPAVGAPPPGDEASSVGAGQPAASSNLQPQPKPSSGGRRRGGQRHKVKSQG
  ACVTPASGC
• Function: Promotes degradation of target mRNA species. Plays a role in the regulation of circadian mRNA stability. Binds GTP and has GTPase activity.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Thrombophilia	DISQR7U7	Strong	Altered Expression	[3]
Autoimmune polyendocrinopathy	DISOLDB2	Limited	Biomarker	[4]
Ebola virus infection	DISJAVM1	Limited	Altered Expression	[5]

11 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 GTP-binding protein 1 (GTPBP1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of GTP-binding protein 1 (GTPBP1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GTP-binding protein 1 (GTPBP1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GTP-binding protein 1 (GTPBP1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GTP-binding protein 1 (GTPBP1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of GTP-binding protein 1 (GTPBP1).	[11]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of GTP-binding protein 1 (GTPBP1).	[12]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of GTP-binding protein 1 (GTPBP1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GTP-binding protein 1 (GTPBP1).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of GTP-binding protein 1 (GTPBP1).	[14]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of GTP-binding protein 1 (GTPBP1).	[17]

3 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 affects the phosphorylation of GTP-binding protein 1 (GTPBP1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of GTP-binding protein 1 (GTPBP1).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of GTP-binding protein 1 (GTPBP1).	[15]

References

• [1] Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat.Neurobiol Aging. 2013 Sep;34(9):2234.e1-7. doi: 10.1016/j.neurobiolaging.2013.03.003. Epub 2013 Apr 12.
• [2] The receptor for beta(2)GP I on membrane of hepatocellular carcinoma cell line SMMC-7721 is annexin II.World J Gastroenterol. 2007 Jun 28;13(24):3364-8. doi: 10.3748/wjg.v13.i24.3364.
• [3] Beta 2-glycoprotein I deficiency and the risk of thrombosis.Thromb Haemost. 1992 Jun 1;67(6):649-53.
• [4] Effect and mechanism of the a2GP I/rh2GP I complex on JEG? cell proliferation, migration and invasion.Mol Med Rep. 2018 Jun;17(6):7505-7512. doi: 10.3892/mmr.2018.8822. Epub 2018 Mar 29.
• [5] Overexpression of Ebola virus envelope GP1 protein.Protein Expr Purif. 2017 Jul;135:45-53. doi: 10.1016/j.pep.2017.04.010. Epub 2017 Apr 27.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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] 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] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] 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.
• [16] 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.
• [17] Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009 Feb 12;177(3):173-80. doi: 10.1016/j.cbi.2008.10.051. Epub 2008 Nov 6.