Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL9HDEY)

• DOT Name: Transmembrane protein 11, mitochondrial (TMEM11)
• Synonyms: Protein PM1; Protein PMI
• Gene Name: TMEM11
• Related Disease:
  MPI-congenital disorder of glycosylation
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Cardiovascular disease
  Hyperinsulinemia
  Medullary thyroid gland carcinoma
  Myocardial infarction
  High blood pressure
  Anxiety
  Anxiety disorder
  Neoplasm
  Non-insulin dependent diabetes
• UniProt ID: TMM11_HUMAN
• Pfam ID: PF14972
• Sequence:
  MAAWGRRRLGPGSSGGSARERVSLSATDCYIVHEIYNGENAQDQFEYELEQALEAQYKYI
  VIEPTRIGDETARWITVGNCLHKTAVLAGTACLFTPLALPLDYSHYISLPAGVLSLACCT
  LYGISWQFDPCCKYQVEYDAYKLSRLPLHTLTSSTPVVLVRKDDLHRKRLHNTIALAALV
  YCVKKIYELYAV
• Function: Plays a role in mitochondrial morphogenesis.
• Reactome Pathway: Cristae formation (R-HSA-8949613)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
MPI-congenital disorder of glycosylation	DISJ394F	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[5]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[6]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Genetic Variation	[7]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[8]
High blood pressure	DISY2OHH	moderate	Biomarker	[9]
Anxiety	DISIJDBA	Limited	Biomarker	[10]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Altered Expression	[11]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[12]

6 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 Transmembrane protein 11, mitochondrial (TMEM11).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 11, mitochondrial (TMEM11).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane protein 11, mitochondrial (TMEM11).	[15]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Transmembrane protein 11, mitochondrial (TMEM11).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transmembrane protein 11, mitochondrial (TMEM11).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 11, mitochondrial (TMEM11).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Transmembrane protein 11, mitochondrial (TMEM11).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transmembrane protein 11, mitochondrial (TMEM11).	[20]

References

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• [2] Lanthanide-doped nanoparticles conjugated with an anti-CD33 antibody and a p53-activating peptide for acute myeloid leukemia therapy.Biomaterials. 2018 Jun;167:132-142. doi: 10.1016/j.biomaterials.2018.03.025. Epub 2018 Mar 14.
• [3] In vivo activation of the p53 tumor suppressor pathway by an engineered cyclotide.J Am Chem Soc. 2013 Aug 7;135(31):11623-11633. doi: 10.1021/ja405108p. Epub 2013 Jul 25.
• [4] Cyclooxygenase 2 RNA message abundance, stability, and hypervariability in sporadic Alzheimer neocortex.J Neurosci Res. 1997 Dec 15;50(6):937-45. doi: 10.1002/(SICI)1097-4547(19971215)50:6<937::AID-JNR4>3.0.CO;2-E.
• [5] Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology.Forensic Sci Int. 2010 Dec 15;203(1-3):99-105. doi: 10.1016/j.forsciint.2010.07.005. Epub 2010 Aug 12.
• [6] Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture.Diabetes Obes Metab. 2014 Aug;16(8):728-38. doi: 10.1111/dom.12274. Epub 2014 Mar 10.
• [7] Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1579-83. doi: 10.1073/pnas.91.4.1579.
• [8] Albumin, a marker for post-operative myocardial damage in cardiac surgery.J Crit Care. 2018 Oct;47:55-60. doi: 10.1016/j.jcrc.2018.06.009. Epub 2018 Jun 6.
• [9] The relationships between arsenic methylation and both skin lesions and hypertension caused by chronic exposure to arsenic in drinking water.Environ Toxicol Pharmacol. 2017 Jul;53:89-94. doi: 10.1016/j.etap.2017.05.009. Epub 2017 May 12.
• [10] An Extract of Artemisia dracunculus L. Promotes Psychological Resilience in a Mouse Model of Depression.Oxid Med Cell Longev. 2018 May 13;2018:7418681. doi: 10.1155/2018/7418681. eCollection 2018.
• [11] Ectopic expression of X-linked lymphocyte-regulated protein pM1 renders tumor cells resistant to antitumor immunity.Cancer Res. 2010 Apr 15;70(8):3062-70. doi: 10.1158/0008-5472.CAN-09-3856.
• [12] Bioactives of Artemisia dracunculus L enhance cellular insulin signaling in primary human skeletal muscle culture.Metabolism. 2008 Jul;57(7 Suppl 1):S58-64. doi: 10.1016/j.metabol.2008.04.003.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] 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.
• [16] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [17] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [18] 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.
• [19] 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.
• [20] 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.