Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1CINQQ)

• DOT Name: Integral membrane protein GPR137B (GPR137B)
• Synonyms: Transmembrane 7 superfamily member 1 protein
• Gene Name: GPR137B
• UniProt ID: G137B_HUMAN
• Sequence:
  MRPERPRPRGSAPGPMETPPWDPARNDSLPPTLTPAVPPYVKLGLTVVYTVFYALLFVFI
  YVQLWLVLRYRHKRLSYQSVFLFLCLFWASLRTVLFSFYFKDFVAANSLSPFVFWLLYCF
  PVCLQFFTLTLMNLYFTQVIFKAKSKYSPELLKYRLPLYLASLFISLVFLLVNLTCAVLV
  KTGNWERKVIVSVRVAINDTLFVLCAVSLSICLYKISKMSLANIYLESKGSSVCQVTAIG
  VTVILLYTSRACYNLFILSFSQNKSVHSFDYDWYNVSDQADLKNQLGDAGYVLFGVVLFV
  WELLPTTLVVYFFRVRNPTKDLTNPGMVPSHGFSPRSYFFDNPRRYDSDDDLAWNIAPQG
  LQGGFAPDYYDWGQQTNSFLAQAGTLQDSTLDPDKPSLG
• Function: Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Interacts with Rag GTPases and increases the lysosomial localization and activity of Rag GTPases and thereby regulates mTORC1 translocation and activity in lysosome. Involved in the regulation of lysosomal morphology and autophagy ; Acts also as a negative regulator of osteoclast activity. Involved in interleukin-4-induced M2 macrophage polarization.
• Tissue Specificity: Expressed in kidney, heart, brain and placenta.

Molecular Interaction Atlas (MIA) of This DOT

21 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 Integral membrane protein GPR137B (GPR137B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Integral membrane protein GPR137B (GPR137B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Integral membrane protein GPR137B (GPR137B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integral membrane protein GPR137B (GPR137B).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Integral membrane protein GPR137B (GPR137B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Integral membrane protein GPR137B (GPR137B).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Integral membrane protein GPR137B (GPR137B).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Integral membrane protein GPR137B (GPR137B).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Integral membrane protein GPR137B (GPR137B).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Integral membrane protein GPR137B (GPR137B).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Integral membrane protein GPR137B (GPR137B).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Integral membrane protein GPR137B (GPR137B).	[12]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Integral membrane protein GPR137B (GPR137B).	[13]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Integral membrane protein GPR137B (GPR137B).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Integral membrane protein GPR137B (GPR137B).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Integral membrane protein GPR137B (GPR137B).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Integral membrane protein GPR137B (GPR137B).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Integral membrane protein GPR137B (GPR137B).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Integral membrane protein GPR137B (GPR137B).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Integral membrane protein GPR137B (GPR137B).	[19]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Integral membrane protein GPR137B (GPR137B).	[20]

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 Integral membrane protein GPR137B (GPR137B).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Integral membrane protein GPR137B (GPR137B).	[15]

References

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• [3] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
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• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [8] 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.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [13] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [16] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [17] 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.
• [18] 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.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.