Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6574BF)

• DOT Name: Protamine-3 (PRM3)
• Synonyms: Sperm protamine P3
• Gene Name: PRM3
• Related Disease:
  Lipid metabolism disorder
  Metabolic disorder
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Atrial fibrillation
  Cardiovascular disease
  Childhood acute lymphoblastic leukemia
  Epilepsy
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Fatty liver disease
  Heritable pulmonary arterial hypertension
  Inflammatory bowel disease
  Influenza
  Neoplasm
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Seminoma
  Synovial sarcoma
  Hepatocellular carcinoma
  Carcinoma of esophagus
  Neoplasm of esophagus
  Omenn syndrome
  Severe combined immunodeficiency
  Squamous cell carcinoma
• UniProt ID: PRM3_HUMAN
• Sequence:
  MGSRCAKLNTGQSPGHSPGHSTGHGRGHESSMKKLMACVSQDNFSLSSAGEEEEEEEEEG
  EEEEKEELPVQGKLLLLEPERQEEGHKDNAEAQQSPEPKRTPS
• Function: Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lipid metabolism disorder	DISEOA7S	Definitive	Biomarker	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[6]
Epilepsy	DISBB28L	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[9]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[10]
Heritable pulmonary arterial hypertension	DISD1Y94	Strong	Genetic Variation	[11]
Inflammatory bowel disease	DISGN23E	Strong	Posttranslational Modification	[12]
Influenza	DIS3PNU3	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[14]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[14]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[15]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[15]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[16]
Synovial sarcoma	DISEZJS7	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[18]
Carcinoma of esophagus	DISS6G4D	Limited	Altered Expression	[8]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[8]
Omenn syndrome	DIS2C887	Limited	Biomarker	[19]
Severe combined immunodeficiency	DIS6MF4Q	Limited	Genetic Variation	[19]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[20]

2 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 Protamine-3 (PRM3).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protamine-3 (PRM3).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protamine-3 (PRM3).	[22]

References

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• [2] Chemotherapy-induced hypomethylation of N-myc downstream-regulated gene 4 in the bone marrow of patients with acute myeloid leukemia.Oncol Lett. 2017 May;13(5):3309-3313. doi: 10.3892/ol.2017.5839. Epub 2017 Mar 10.
• [3] Hypermethylation and aberrant expression of secreted frizzled-related protein genes in pancreatic cancer.World J Gastroenterol. 2008 Jun 7;14(21):3421-4. doi: 10.3748/wjg.14.3421.
• [4] APOE 4 Carriers Show Delayed Recovery of Verbal Memory and Smaller Entorhinal Volume in the First Year After Ischemic Stroke.J Alzheimers Dis. 2019;71(1):245-259. doi: 10.3233/JAD-190566.
• [5] A Potential Role of Esophageal Cancer Related Gene-4 for Atrial Fibrillation.Sci Rep. 2017 Jun 2;7(1):2717. doi: 10.1038/s41598-017-02902-x.
• [6] Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
• [7] C2-lacking isoform of Nedd4-2 regulates excitatory synaptic strength through GluA1 ubiquitination-independent mechanisms.J Neurochem. 2019 Nov;151(3):289-300. doi: 10.1111/jnc.14840. Epub 2019 Aug 25.
• [8] Ecrg4 deficiency extends the replicative capacity of neural stem cells in a Foxg1-dependent manner.Development. 2019 Feb 18;146(4):dev168120. doi: 10.1242/dev.168120.
• [9] Impact of alcohol dehydrogenase gene 4 polymorphisms on esophageal squamous cell carcinoma risk in a Chinese population.PLoS One. 2015 Jun 3;10(6):e0127304. doi: 10.1371/journal.pone.0127304. eCollection 2015.
• [10] SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c.Diabetes. 2018 Nov;67(11):2227-2238. doi: 10.2337/db18-0184. Epub 2018 Sep 4.
• [11] Genetics of pulmonary hypertension in the clinic.Curr Opin Pulm Med. 2017 Sep;23(5):386-391. doi: 10.1097/MCP.0000000000000414.
• [12] DNA Methylation and Mutation of Small Colonic Neoplasms in Ulcerative Colitis and Crohn's Colitis: Implications for Surveillance.Inflamm Bowel Dis. 2016 Jul;22(7):1559-67. doi: 10.1097/MIB.0000000000000795.
• [13] From the National Institutes of Health. Summary of a meeting on the origin of pandemic influenza viruses.J Infect Dis. 1984 Jan;149(1):108-15. doi: 10.1093/infdis/149.1.108.
• [14] Regulated expression of the TP isoform of the human T prostanoid receptor by the tumour suppressors FOXP1 and NKX3.1: Implications for the role of thromboxane in prostate cancer.Biochim Biophys Acta Mol Basis Dis. 2017 Dec;1863(12):3153-3169. doi: 10.1016/j.bbadis.2017.09.005. Epub 2017 Sep 8.
• [15] The impact of interleukin-10 (IL-10) gene 4 polymorphisms on peripheral blood IL-10 variation and prostate cancer risk based on published studies.Oncotarget. 2017 Jul 11;8(28):45994-46005. doi: 10.18632/oncotarget.17522.
• [16] Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4.Cell Mol Life Sci. 2005 Oct;62(19-20):2359-68. doi: 10.1007/s00018-005-5250-9.
• [17] Amplification of the c-myc proto-oncogene in soft tissue sarcomas.Oncology. 1994 Jan-Feb;51(1):13-7. doi: 10.1159/000227302.
• [18] Downregulation of esophageal cancer-related gene 4 promotes proliferation and migration of hepatocellular carcinoma.Oncol Lett. 2017 Sep;14(3):3689-3696. doi: 10.3892/ol.2017.6616. Epub 2017 Jul 20.
• [19] Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.Clin Exp Immunol. 2014 Jun;176(3):380-6. doi: 10.1111/cei.12273.
• [20] Esophageal cancer related gene-4 inhibits the migration and proliferation of oral squamous cell carcinoma through BC200 lncRNA/MMP-9 and -13 signaling pathway.Cell Signal. 2019 Oct;62:109327. doi: 10.1016/j.cellsig.2019.05.012. Epub 2019 May 29.
• [21] 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.
• [22] 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.
• [23] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.