Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH4EEMI)

• DOT Name: Prion-like protein doppel (PRND)
• Synonyms: PrPLP; Prion protein 2
• Gene Name: PRND
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Astrocytoma
  Bone osteosarcoma
  Cerebellar ataxia
  Neoplasm
  Osteosarcoma
  Prion disease
  Anxiety
  Anxiety disorder
• UniProt ID: PRND_HUMAN
• PDB ID: 1LG4
• Pfam ID: PF11466 ; PF00377
• Sequence:
  MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFI
  KQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEF
  QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK
• Function: Required for normal acrosome reaction and for normal male fertility. Can bind Cu(2+).
• Tissue Specificity: Expressed in testis, in Sertoli cells, ejaculated spermatozoa and in seminal fluid (at protein level).
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Prion disease	DISOUMB0	Strong	Biomarker	[6]
Anxiety	DISIJDBA	Limited	Genetic Variation	[2]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[2]

2 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 Prion-like protein doppel (PRND).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Prion-like protein doppel (PRND).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prion-like protein doppel (PRND).	[8]

References

• [1] Diagnostic value of PRND gene expression profiles in astrocytomas: relationship to tumor grades of malignancy.Oncol Rep. 2007 May;17(5):989-96. doi: 10.3892/or.17.5.989.
• [2] PRND 3'UTR polymorphism may be associated with behavioral disturbances in Alzheimer disease.Prion. 2012 Jan-Mar;6(1):73-80. doi: 10.4161/pri.6.1.18428.
• [3] Altered cellular distribution and sub-cellular sorting of doppel (Dpl) protein in human astrocytoma cell lines.Cell Oncol. 2008;30(4):337-47. doi: 10.3233/clo-2008-0429.
• [4] Prion proteins (PRNP and PRND) are over-expressed in osteosarcoma.J Orthop Res. 2012 Jun;30(6):1004-12. doi: 10.1002/jor.22034. Epub 2011 Dec 6.
• [5] Prion-like protein Doppel expression is not modified in scrapie-infected cells and in the brains of patients with Creutzfeldt-Jakob disease.FEBS Lett. 2003 Feb 11;536(1-3):61-5. doi: 10.1016/s0014-5793(03)00012-7.
• [6] First report of polymorphisms in the prion-like protein gene (PRND): implications for human prion diseases.Neurosci Lett. 2000 Jun 2;286(2):144-8. doi: 10.1016/s0304-3940(00)01100-9.
• [7] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [8] 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.
• [9] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.