Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0KUBBI)

• DOT Name: Transmembrane protein 158 (TMEM158)
• Synonyms: 40 kDa BINP-binding protein; p40BBP; Ras-induced senescence protein 1
• Gene Name: TMEM158
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Epithelial ovarian cancer
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Rheumatoid arthritis
  Carcinoma
  Colorectal carcinoma
  Pancreatic cancer
  Osteomyelitis
• UniProt ID: TM158_HUMAN
• Sequence:
  MLPLLAALLAAACPLPPVRGGAADAPGLLGVPSNASVNASSADEPIAPRLLASAAPGPPE
  RPGPEEAAAAAAPCNISVQRQMLSSLLVRWGRPRGFQCDLLLFSTNAHGRAFFAAAFHRV
  GPPLLIEHLGLAAGGAQQDLRLCVGCGWVRGRRTGRLRPAAAPSAAAATAGAPTALPAYP
  AAEPPGPLWLQGEPLHFCCLDFSLEELQGEPGWRLNRKPIESTLVACFMTLVIVVWSVAA
  LIWPVPIIAGFLPNGMEQRRTTASTTAATPAAVPAGTTAAAAAAAAAAAAAAVTSGVATK
• Function: Receptor for brain injury-derived neurotrophic peptide (BINP), a synthetic 13-mer peptide.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	moderate	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[6]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[3]
Osteomyelitis	DIS0VUZL	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Transmembrane protein 158 (TMEM158) affects the response to substance of DTI-015.	[31]

23 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 Transmembrane protein 158 (TMEM158).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 158 (TMEM158).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 158 (TMEM158).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 158 (TMEM158).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 158 (TMEM158).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane protein 158 (TMEM158).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 158 (TMEM158).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transmembrane protein 158 (TMEM158).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transmembrane protein 158 (TMEM158).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transmembrane protein 158 (TMEM158).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Transmembrane protein 158 (TMEM158).	[18]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Transmembrane protein 158 (TMEM158).	[19]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Transmembrane protein 158 (TMEM158).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein 158 (TMEM158).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 158 (TMEM158).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 158 (TMEM158).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 158 (TMEM158).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transmembrane protein 158 (TMEM158).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane protein 158 (TMEM158).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane protein 158 (TMEM158).	[27]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Transmembrane protein 158 (TMEM158).	[28]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Transmembrane protein 158 (TMEM158).	[29]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Transmembrane protein 158 (TMEM158).	[30]

References

• [1] Analysis of the candidate tumor suppressor Ris-1 in primary human breast carcinomas.Mutat Res. 2006 Feb 22;594(1-2):78-85. doi: 10.1016/j.mrfmmm.2005.07.017. Epub 2005 Nov 8.
• [2] Overexpression of TMEM158 contributes to ovarian carcinogenesis.J Exp Clin Cancer Res. 2015 Aug 4;34(1):75. doi: 10.1186/s13046-015-0193-y.
• [3] TMEM158 promotes pancreatic cancer aggressiveness by activation of TGF1 and PI3K/AKT signaling pathway.J Cell Physiol. 2020 Mar;235(3):2761-2775. doi: 10.1002/jcp.29181. Epub 2019 Sep 17.
• [4] TMEM158 and FBLP1 as novel marker genes of cisplatin sensitivity in non-small cell lung cancer cells.Exp Lung Res. 2012 Nov;38(9-10):463-74. doi: 10.3109/01902148.2012.731625.
• [5] Topical all-trans retinoic acid (RA) induces an early, coordinated increase in RA-inducible skin-specific gene/psoriasin and cellular RA-binding protein II mRNA levels which precedes skin erythema.Arch Dermatol Res. 1996 Oct;288(11):664-9. doi: 10.1007/BF02505275.
• [6] Silencing of TMEM158 Inhibits Tumorigenesis and Multidrug Resistance in Colorectal Cancer.Nutr Cancer. 2020;72(4):662-671. doi: 10.1080/01635581.2019.1650192. Epub 2019 Aug 7.
• [7] A bone sialoprotein-binding protein from Staphylococcus aureus: a member of the staphylococcal Sdr family.Biochem J. 2000 Feb 1;345 Pt 3(Pt 3):611-9.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [16] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [17] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [18] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [19] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [20] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [23] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [24] 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.
• [25] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [26] 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.
• [27] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [28] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [29] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
• [30] Analysis of lead toxicity in human cells. BMC Genomics. 2012 Jul 27;13:344.
• [31] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.