Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYSOQS0)

• DOT Name: Tudor domain-containing protein 5 (TDRD5)
• Gene Name: TDRD5
• Related Disease:
  Hepatocellular carcinoma
  Testicular cancer
• UniProt ID: TDRD5_HUMAN
• PDB ID: 3S93
• Pfam ID: PF12872 ; PF00567
• Sequence:
  MSEQERIQECLRKEIRSLLISTKDGLSPQELEKEYLLMVGNHLPLRILGYRSTMELVLDM
  PDVVRVCPGAGGTVILKAIPDESTKGIASLVAKQRSSHKLRNSMHKGRPSIYSGPRSHRR
  VPYRGRVAPILPAVVKSELKDLLALSPVLLSDFEKAFAKRFGRSFQYMQYGFLSMFEVLN
  AASDVISVEQTRAGSLLMLKKSVTEEKPRGCPAGKIFTQPFRMKQGSYSTGFPVAKPCFS
  QPTSNMEPPKQIMSMEKTSKLNVVETSRLNHTEKLNQLENTFKSVIAQIGPGGTISSELK
  HKIKFVVSKFPEGLFISKLLGEYEVIFKEQLSPKKLGFLNVTELVGALSDILHVEFRKGH
  QDLLVFDADKKPLPPVQSDKKIEAKACVSSPPRNSLSTAAVKETVWNCPSKKQKEPQQKI
  CKKPNLVVKPLQLQVETNKSELNLAMANHDIPPDAVPNKKLCRLPPLDTSSLIGVFVEYI
  ISPSQFYIRIYSRDSSELLEDMMIEMRRCYSNQLVSDRYVMPECFIQPGHLCCVRISEDK
  WWYRVIIHRVLEKQEVEVFYPDFGNIGIVQKSSLRFLKCCYTKLPAQAIPCSLAWVRPVE
  EHWTSKAILQFQKLCGLKPLVGVVDEYVDGILNIFLCDTSSNEDVYFHHVLRTEGHAIVC
  RENISSKGFSELNPLALYTTSSGGPEDIVLTELGYPSQQHYFNEDRKISPQSKESELRIL
  DEIPTGMPCLESVTIGDDIWDENWLPLQAKMGKGGDAASHLFTASLGGKNQYSSCKEMPQ
  KDWCFSTPKDTWDDSWQPSGLVNGTKVEVHKPEVLGAQEKNTGTNRTQKQLDINGSSDSS
  TLPKLEEFCTSLTQSEQSADGSQSEPNNSQTQPKQIQLSTAAPCSTTAVDDSAEKPSGSV
  ESSPEILKNEDFSSSRAITLYKDKRQESVDQLSLILSYECQISQKLYIPRSTATAALGAA
  ARLATSRSLLHWYPSVKRMEA
• Function: Required during spermiogenesis to participate in the repression transposable elements and prevent their mobilization, which is essential for the germline integrity. Probably 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. Required for chromatoid body (CB) assembly.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[2]

3 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 Tudor domain-containing protein 5 (TDRD5).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tudor domain-containing protein 5 (TDRD5).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tudor domain-containing protein 5 (TDRD5).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Tudor domain-containing protein 5 (TDRD5).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tudor domain-containing protein 5 (TDRD5).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tudor domain-containing protein 5 (TDRD5).	[4]

References

• [1] Genomewide investigation of the clinical implications and molecular mechanism of long noncoding RNA LINC00668 and proteincoding genes in hepatocellular carcinoma.Int J Oncol. 2019 Oct;55(4):860-878. doi: 10.3892/ijo.2019.4858. Epub 2019 Aug 14.
• [2] Tudor domain-containing protein 4 as a potential cancer/testis antigen in liver cancer.Tohoku J Exp Med. 2011 May;224(1):41-6. doi: 10.1620/tjem.224.41.
• [3] 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.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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.
• [7] 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.