Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZBZ4MC)

• DOT Name: Transmembrane protein 201 (TMEM201)
• Synonyms: Spindle-associated membrane protein 1
• Gene Name: TMEM201
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Aortic valve disorder
  Emery-Dreifuss muscular dystrophy
  Emery-Dreifuss muscular dystrophy 2, autosomal dominant
  Inflammatory bowel disease
  Neoplasm
  Premature aging syndrome
  Crohn disease
  Bacterial infection
  Colitis
• UniProt ID: TM201_HUMAN
• Pfam ID: PF10476 ; PF09779
• Sequence:
  MEGVSALLARCPTAGLAGGLGVTACAAAGVLLYRIARRMKPTHTMVNCWFCNQDTLVPYG
  NRNCWDCPHCEQYNGFQENGDYNKPIPAQYLEHLNHVVSSAPSLRDPSQPQQWVSSQVLL
  CKRCNHHQTTKIKQLAAFAPREEGRYDEEVEVYRHHLEQMYKLCRPCQAAVEYYIKHQNR
  QLRALLLSHQFKRREADQTHAQNFSSAVKSPVQVILLRALAFLACAFLLTTALYGASGHF
  APGTTVPLALPPGGNGSATPDNGTTPGAEGWRQLLGLLPEHMAEKLCEAWAFGQSHQTGV
  VALGLLTCLLAMLLAGRIRLRRIDAFCTCLWALLLGLHLAEQHLQAASPSWLDTLKFSTT
  SLCCLVGFTAAVATRKATGPRRFRPRRFFPGDSAGLFPTSPSLAIPHPSVGGSPASLFIP
  SPPSFLPLANQQLFRSPRRTSPSSLPGRLSRALSLGTIPSLTRADSGYLFSGSRPPSQVS
  RSGEFPVSDYFSLLSGSCPSSPLPSPAPSVAGSVASSSGSLRHRRPLISPARLNLKGQKL
  LLFPSPPGEAPTTPSSSDEHSPHNGSLFTMEPPHVPRKPPLQDVKHALDLRSKLERGSAC
  SNRSIKKEDDSSQSSTCVVDTTTRGCSEEAATWRGRFGPSLVRGLLAVSLAANALFTSVF
  LYQSLR
• Function: Involved in nuclear movement during fibroblast polarization and migration. Proposed to be involved in actin-dependent nuclear movement via association with transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow. Overexpression can recruit Ran GTPase to the nuclear periphery ; [Isoform 2]: May define a distinct membrane domain in the vicinity of the mitotic spindle. Involved in the organization of the nuclear envelope implicating EMD, SUN1 and A-type lamina.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Aortic valve disorder	DISKLYD7	Strong	Biomarker	[3]
Emery-Dreifuss muscular dystrophy	DISYTPR5	Strong	Biomarker	[4]
Emery-Dreifuss muscular dystrophy 2, autosomal dominant	DIS4FT32	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Premature aging syndrome	DIS51AGT	Strong	Biomarker	[7]
Crohn disease	DIS2C5Q8	moderate	Biomarker	[5]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[8]
Colitis	DISAF7DD	Limited	Biomarker	[1]

4 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 Transmembrane protein 201 (TMEM201).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane protein 201 (TMEM201).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Transmembrane protein 201 (TMEM201).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transmembrane protein 201 (TMEM201).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 201 (TMEM201).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 201 (TMEM201).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 201 (TMEM201).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane protein 201 (TMEM201).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane protein 201 (TMEM201).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transmembrane protein 201 (TMEM201).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane protein 201 (TMEM201).	[16]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Transmembrane protein 201 (TMEM201).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 201 (TMEM201).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 201 (TMEM201).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transmembrane protein 201 (TMEM201).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane protein 201 (TMEM201).	[23]

References

• [1] A novel model of colitis-associated cancer in SAMP1/YitFc mice with Crohn's disease-like ileitis.PLoS One. 2017 Mar 16;12(3):e0174121. doi: 10.1371/journal.pone.0174121. eCollection 2017.
• [2] Ginsenoside Rg1 and Acori Graminei Rhizoma Attenuates Neuron Cell Apoptosis by Promoting the Expression of miR-873-5p in Alzheimer's Disease.Neurochem Res. 2018 Aug;43(8):1529-1538. doi: 10.1007/s11064-018-2567-y. Epub 2018 Jun 20.
• [3] Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.Hypertension. 2018 May;71(5):877-885. doi: 10.1161/HYPERTENSIONAHA.117.10560. Epub 2018 Mar 26.
• [4] Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy.Cells. 2018 Oct 15;7(10):170. doi: 10.3390/cells7100170.
• [5] Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients.Inflamm Bowel Dis. 2020 Feb 11;26(3):347-359. doi: 10.1093/ibd/izz242.
• [6] Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice.Biochem Biophys Res Commun. 2017 Nov 4;493(1):252-257. doi: 10.1016/j.bbrc.2017.09.035. Epub 2017 Sep 9.
• [7] Antioxidant modifications induced by the new metformin derivative HL156A regulate metabolic reprogramming in SAMP1/kl (-/-) mice.Aging (Albany NY). 2018 Sep 16;10(9):2338-2355. doi: 10.18632/aging.101549.
• [8] Senescence-accelerated mice (SAMP1/TA-1) treated repeatedly with lipopolysaccharide develop a condition that resembles hemophagocytic lymphohistiocytosis.Haematologica. 2019 Oct;104(10):1995-2005. doi: 10.3324/haematol.2018.209551. Epub 2019 Feb 28.
• [9] 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.
• [10] 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.
• [11] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] 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.
• [15] 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.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [18] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [23] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.