Details of Drug Off-Target (DOT)

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

• DOT Name: Protamine-2 (PRM2)
• Synonyms: Sperm histone P2; Sperm protamine P2
• Gene Name: PRM2
• Related Disease:
  Azoospermia
  Male infertility
  Polycythemia vera
• UniProt ID: PRM2_HUMAN
• Pfam ID: PF00841
• Sequence:
  MVRYRVRSLSERSHEVYRQQLHGQEQGHHGQEEQGLSPEHVEVYERTHGQSHYRRRHCSR
  RRLHRIHRRQHRSCRRRKRRSCRHRRRHRRGCRTRKRTCRRH
• 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.
• Tissue Specificity: Testis.
• Reactome Pathway: Replacement of protamines by nucleosomes in the male pronucleus (R-HSA-9821993)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Polycythemia vera	DISB5FPO	Strong	Genetic Variation	[3]

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-2 (PRM2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protamine-2 (PRM2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Protamine-2 (PRM2).	[5]

References

• [1] Carnitine/organic cation transporter 2 (OCTN2) contributes to rat epididymal epithelial cell growth and proliferation.Biomed Pharmacother. 2017 Sep;93:444-450. doi: 10.1016/j.biopha.2017.06.057. Epub 2017 Jun 27.
• [2] The c.-190 C>A transversion in promoter region of protamine 1 gene as a genetic risk factor in Egyptian men with idiopathic infertility.Andrologia. 2019 Oct;51(9):e13367. doi: 10.1111/and.13367. Epub 2019 Jul 9.
• [3] Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.Clin Immunol. 2007 Mar;122(3):279-87. doi: 10.1016/j.clim.2006.10.006. Epub 2006 Nov 17.
• [4] 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.
• [5] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [6] 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.