Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0CBCI3)

• DOT Name: Tudor domain-containing protein 1 (TDRD1)
• Synonyms: Cancer/testis antigen 41.1; CT41.1
• Gene Name: TDRD1
• Related Disease:
  Male infertility
  Prostate adenocarcinoma
  Prostate neoplasm
  Testicular cancer
  Testicular germ cell tumor
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Benign prostatic hyperplasia
• UniProt ID: TDRD1_HUMAN
• PDB ID: 5M9N
• Pfam ID: PF00567 ; PF01753
• Sequence:
  MSVKSPFNVMSRNNLEAPPCKMTEPFNFEKNENKLPPHESLRSPGTLPNHPNFRLKSSEN
  GNKKNNFLLCEQTKQYLASQEDNSVSSNPNGINGEVVGSKGDRKKLPAGNSVSPPSAESN
  SPPKEVNIKPGNNVRPAKSKKLNKLVENSLSISNPGLFTSLGPPLRSTTCHRCGLFGSLR
  CSQCKQTYYCSTACQRRDWSAHSIVCRPVQPNFHKLENKSSIETKDVEVNNKSDCPLGVT
  KEIAIWAERIMFSDLRSLQLKKTMEIKGTVTEFKHPGDFYVQLYSSEVLEYMNQLSASLK
  ETYANVHEKDYIPVKGEVCIAKYTVDQTWNRAIIQNVDVQQKKAHVLYIDYGNEEIIPLN
  RIYHLNRNIDLFPPCAIKCFVANVIPAEGNWSSDCIKATKPLLMEQYCSIKIVDILEEEV
  VTFAVEVELPNSGKLLDHVLIEMGYGLKPSGQDSKKENADQSDPEDVGKMTTENNIVVDK
  SDLIPKVLTLNVGDEFCGVVAHIQTPEDFFCQQLQSGRKLAELQASLSKYCDQLPPRSDF
  YPAIGDICCAQFSEDDQWYRASVLAYASEESVLVGYVDYGNFEILSLMRLCPIIPKLLEL
  PMQAIKCVLAGVKPSLGIWTPEAICLMKKLVQNKIITVKVVDKLENSSLVELIDKSETPH
  VSVSKVLLDAGFAVGEQSMVTDKPSDVKETSVPLGVEGKVNPLEWTWVELGVDQTVDVVV
  CVIYSPGEFYCHVLKEDALKKLNDLNKSLAEHCQQKLPNGFKAEIGQPCCAFFAGDGSWY
  RALVKEILPNGHVKVHFVDYGNIEEVTADELRMISSTFLNLPFQGIRCQLADIQSRNKHW
  SEEAITRFQMCVAGIKLQARVVEVTENGIGVELTDLSTCYPRIISDVLIDEHLVLKSASP
  HKDLPNDRLVNKHELQVHVQGLQATSSAEQWKTIELPVDKTIQANVLEIISPNLFYALPK
  GMPENQEKLCMLTAELLEYCNAPKSRPPYRPRIGDACCAKYTSDDFWYRAVVLGTSDTDV
  EVLYADYGNIETLPLCRVQPITSSHLALPFQIIRCSLEGLMELNGSSSQLIIMLLKNFML
  NQNVMLSVKGITKNVHTVSVEKCSENGTVDVADKLVTFGLAKNITPQRQSALNTEKMYRM
  NCCCTELQKQVEKHEHILLFLLNNSTNQNKFIEMKKLLKS
• Function: Plays a central role during spermatogenesis by participating in the repression 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 governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins.
• Tissue Specificity: Testis and ovary specific. Also expressed in several cancers.
• Reactome Pathway: PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Biomarker	[1]
Prostate adenocarcinoma	DISBZYU8	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[3]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[4]
Testicular germ cell tumor	DIS5RN24	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Disputed	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Disputed	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[7]
Benign prostatic hyperplasia	DISI3CW2	Limited	Biomarker	[8]

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 Tudor domain-containing protein 1 (TDRD1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tudor domain-containing protein 1 (TDRD1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tudor domain-containing protein 1 (TDRD1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tudor domain-containing protein 1 (TDRD1).	[11]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Tudor domain-containing protein 1 (TDRD1).	[12]

References

• [1] Transcriptomic Analysis Reveals Insights on Male Infertility in Octopus maya Under Chronic Thermal Stress.Front Physiol. 2019 Jan 15;9:1920. doi: 10.3389/fphys.2018.01920. eCollection 2018.
• [2] Analysis of competing endogenous RNA network to identify the key RNAs associated with prostate adenocarcinoma.Pathol Res Pract. 2018 Nov;214(11):1811-1817. doi: 10.1016/j.prp.2018.08.029. Epub 2018 Aug 29.
• [3] The Germ Cell Gene TDRD1 as an ERG Target Gene and a Novel Prostate Cancer Biomarker.Prostate. 2016 Oct;76(14):1271-84. doi: 10.1002/pros.23213. Epub 2016 Jun 8.
• [4] 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.
• [5] Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis.Epigenetics. 2014 Jan;9(1):113-8. doi: 10.4161/epi.27237. Epub 2013 Nov 18.
• [6] Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells.BJU Int. 2019 May;123 Suppl 5:27-35. doi: 10.1111/bju.14695.
• [7] Stratification of aggressive prostate cancer from indolent disease-Prospective controlled trial utilizing expression of 11 genes in apparently benign tissue.Urol Oncol. 2016 Jun;34(6):255.e15-22. doi: 10.1016/j.urolonc.2015.12.014. Epub 2016 Feb 5.
• [8] Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer.J Cancer Res Clin Oncol. 2014 Nov;140(11):1849-61. doi: 10.1007/s00432-014-1738-8. Epub 2014 Jun 18.
• [9] 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.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [12] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [13] 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.