Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ1B8R4)

• DOT Name: Piwi-like protein 3 (PIWIL3)
• Gene Name: PIWIL3
• Related Disease:
  Advanced cancer
  Oligospermia
  Gastric cancer
  Stomach cancer
  Metastatic malignant neoplasm
  Metastatic melanoma
  Neoplasm
• UniProt ID: PIWL3_HUMAN
• Pfam ID: PF02170 ; PF02171
• Sequence:
  MPGRARTRARGRARRRESYQQEAPGGPRAPGSATTQEPPQLQSTPRPLQEEVPVVRPLQP
  RAARGGAGGGAQSQGVKEPGPEAGLHTAPLQERRIGGVFQDLVVNTRQDMKHVKDSKTGS
  EGTVVQLLANHFRVISRPQWVAYKYNVDYKPDIEDGNLRTILLDQHRRKFGERHIFDGNS
  LLLSRPLKERRVEWLSTTKDKNIVKITVEFSKELTPTSPDCLRYYNILFRRTFKLLDFEQ
  VGRNYYTKKKAIQLYRHGTSLEIWLGYVTSVLQYENSITLCADVSHKLLRIETAYDFIKR
  TSAQAQTGNIREEVTNKLIGSIVLTKYNNKTYRVDDIDWKQNPEDTFNKSDGSKITYIDY
  YRQQHKEIVTVKKQPLLVSQGRWKKGLTGTQREPILLIPQLCHMTGLTDEICKDYSIVKE
  LAKHTRLSPRRRHHTLKEFINTLQDNKKVRELLQLWDLKFDTNFLSVPGRVLKNANIVQG
  RRMVKANSQGDWSREIRELPLLNAMPLHSWLILYSRSSHREAMSLKGHLQSVTAPMGITM
  KPAEMIEVDGDANSYIDTLRKYTRPTLQMGMSCLLVFKVICILPNDDKRRYDSIKRYLCT
  KCPIPSQCVVKKTLEKVQARTIVTKIAQQMNCKMGGALWKVETDVQRTMFVGIDCFHDIV
  NRQKSIAGFVASTNAELTKWYSQCVIQKTGEELVKELEICLKAALDVWCKNESSMPHSVI
  VYRDGVGDGQLQALLDHEAKKMSTYLKTISPNNFTLAFIVVKKRINTRFFLKHGSNFQNP
  PPGTVIDVELTRNEWYDFFIVSQSVQDGTVTPTHYNVIYDTIGLSPDTVQRLTYCLCHMY
  YNLPGIIRVPAPCHYAHKLAYLVGQSIHQEPNRSLSTRLFYL
• Function: May play a role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation.
• Tissue Specificity: Expressed in testis.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Oligospermia	DIS6YJF3	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[3]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[4]
Metastatic melanoma	DISSL43L	Limited	Altered Expression	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]

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 Piwi-like protein 3 (PIWIL3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Piwi-like protein 3 (PIWIL3).	[6]

References

• [1] Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells.J Am Chem Soc. 2017 Feb 1;139(4):1400-1403. doi: 10.1021/jacs.6b11751. Epub 2017 Jan 23.
• [2] Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population.Hum Reprod. 2010 Dec;25(12):2955-61. doi: 10.1093/humrep/deq274. Epub 2010 Oct 11.
• [3] Downregulation of Piwil3 suppresses cell proliferation, migration and invasion in gastric cancer.Cancer Biomark. 2017 Dec 6;20(4):499-509. doi: 10.3233/CBM-170324.
• [4] Expression of PIWIL3 in primary and metastatic melanoma.J Cancer Res Clin Oncol. 2017 Mar;143(3):433-437. doi: 10.1007/s00432-016-2305-2. Epub 2016 Nov 17.
• [5] 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.
• [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.