Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEUG8RL)

• DOT Name: Paraneoplastic antigen Ma1 (PNMA1)
• Synonyms: 37 kDa neuronal protein; Neuron- and testis-specific protein 1
• Gene Name: PNMA1
• Related Disease:
  Hepatocellular carcinoma
  Nervous system inflammation
• UniProt ID: PNMA1_HUMAN
• Pfam ID: PF14893 ; PF20846
• Sequence:
  MAMTLLEDWCRGMDVNSQRALLVWGIPVNCDEAEIEETLQAAMPQVSYRMLGRMFWREEN
  AKAALLELTGAVDYAAIPREMPGKGGVWKVLFKPPTSDAEFLERLHLFLAREGWTVQDVA
  RVLGFQNPTPTPGPEMPAEMLNYILDNVIQPLVESIWYKRLTLFSGRDIPGPGEETFDPW
  LEHTNEVLEEWQVSDVEKRRRLMESLRGPAADVIRILKSNNPAITTAECLKALEQVFGSV
  ESSRDAQIKFLNTYQNPGEKLSAYVIRLEPLLQKVVEKGAIDKDNVNQARLEQVIAGANH
  SGAIRRQLWLTGAGEGPAPNLFQLLVQIREEEAKEEEEEAEATLLQLGLEGHF
• Tissue Specificity: Testis- and brain-specific. In some cancer patients, specifically expressed by paraneoplastic tumor cells.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[1]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[2]

17 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 Paraneoplastic antigen Ma1 (PNMA1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[12]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[13]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[13]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Paraneoplastic antigen Ma1 (PNMA1).	[14]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[18]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Paraneoplastic antigen Ma1 (PNMA1).	[19]

1 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 Paraneoplastic antigen Ma1 (PNMA1).	[9]

References

• [1] PNMA1, regulated by miR-33a-5p, promotes proliferation and EMT in hepatocellular carcinoma by activating the Wnt/-catenin pathway.Biomed Pharmacother. 2018 Dec;108:492-499. doi: 10.1016/j.biopha.2018.09.059. Epub 2018 Sep 19.
• [2] Modelling paraneoplastic CNS disease: T-cells specific for the onconeuronal antigen PNMA1 mediate autoimmune encephalomyelitis in the rat.Brain. 2004 Aug;127(Pt 8):1822-30. doi: 10.1093/brain/awh205. Epub 2004 Jun 16.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [13] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [16] 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.
• [17] 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.
• [18] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [19] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.