Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6HWA11)

• DOT Name: Sperm protamine P1 (PRM1)
• Synonyms: Cysteine-rich protamine
• Gene Name: PRM1
• Related Disease:
  Azoospermia
  Colon cancer
  Colon carcinoma
  Male infertility
  Oligospermia
  Prostate adenocarcinoma
  Breast cancer
  Childhood kidney Wilms tumor
  Neoplasm
  Wilms tumor
• UniProt ID: HSP1_HUMAN
• Pfam ID: PF00260
• Sequence: MARYRCCRSQSRSRYYRQRQRSRRRRRRSCQTRRRAMRCCRPRYRPRCRRH
• 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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[3]
Oligospermia	DIS6YJF3	Strong	Altered Expression	[4]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[6]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Wilms tumor	DISB6T16	Limited	Biomarker	[6]

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 Sperm protamine P1 (PRM1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sperm protamine P1 (PRM1).	[8]

References

• [1] Could analysis of testis-specific genes, as biomarkers in seminal plasma, predict presence of focal spermatogenesis in non-obstructive azoospermia?.Andrologia. 2020 Mar;52(2):e13483. doi: 10.1111/and.13483. Epub 2019 Dec 3.
• [2] Impact of protamine I on colon cancer proliferation, invasion, migration, diagnosis and prognosis.Biol Chem. 2018 Feb 23;399(3):265-275. doi: 10.1515/hsz-2017-0222.
• [3] 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.
• [4] Influence of variation in global sperm DNA methylation level on the expression level of protamine genes and human semen parameters.Andrologia. 2020 Feb;52(1):e13484. doi: 10.1111/and.13484. Epub 2019 Nov 24.
• [5] 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.
• [6] Transcriptional regulation of the human thromboxane A2 receptor gene by Wilms' tumor (WT)1 and hypermethylated in cancer (HIC) 1 in prostate and breast cancers.Biochim Biophys Acta. 2014 Jun;1839(6):476-92. doi: 10.1016/j.bbagrm.2014.04.010. Epub 2014 Apr 18.
• [7] 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.
• [8] 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.