Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW2UL4V)

DOT Name Tudor domain-containing protein 6 (TDRD6)
Synonyms Antigen NY-CO-45; Cancer/testis antigen 41.2; CT41.2
Gene Name TDRD6
Related Disease
Colon cancer ( )
Colon carcinoma ( )
Male infertility ( )
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation ( )
Oligospermia ( )
Schizophrenia ( )
UniProt ID
TDRD6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00567
Sequence
MCSTPGMPAPGASLALRVSFVDVHPDVIPVQLWGLVGERRGEYLRLSREIQEAAATRGQW
ALGSASASPGELCLVQVGLLWHRCRVVSRQAQESRVFLLDEGRTITAGAGSLAPGRREFF
NLPSEVLGCVLAGLVPAGCGAGSGEPPQHWPADAVDFLSNLQGKEVHGCVLDVLLLHRLV
LLEVPDVFQQMRELGLARRVPDSLFRSLLERYLTAATASVGSGVPVLSRVPLKQKQPGLD
YFYPQLQLGVTEAVVITQVCHPHRIHCQLRSVSQEIHRLSESMAQVYRGSTGTGDENSTS
ATWEEREESPDKPGSPCASCGLDGHWYRALLLETFRPQRCAQVLHVDYGRKELVSCSSLR
YLLPEYFRMPVVTYPCALYGLWDGGRGWSRSQVGDLKTLILGKAVNAKIEFYCSFEHVYY
VSLYGEDGINLNRVFGVQSCCLADRVLQSQATEEEEPETSQSQSPAEEVDEEISLPALRS
IRLKMNAFYDAQVEFVKNPSEFWIRLRKHNVTFSKLMRRMCGFYSSASKLDGVVLKPEPD
DLCCVKWKENGYYRAIVTKLDDKSVDVFLVDRGNSENVDWYDVRMLLPQFRQLPILAVKC
TLADIWPLGKTWSQEAVSFFKKTVLHKELVIHILDKQDHQYVIEILDESRTGEENISKVI
AQAGYAKYQEFETKENILVNAHSPGHVSNHFTTESNKIPFAKTGEGEQKAKRENKTTSVS
KALSDTTVVTNGSTELVVQEKVKRASVYFPLMQNCLEIKPGSSSKGELEVGSTVEVRVSY
VENPGYFWCQLTRNIQGLKTLMSDIQYYCKNTAAPHQRNTLACLAKRTVNRQWSRALISG
IQSVEHVNVTFVDYGDREMVSVKNIYSISEEFLKVKAQAFRCSLYNLIQPVGQNPFVWDV
KAIQAFNEFIDNAWQKNLELKCTIFALASINEELFNIVDLLTPFQSACHFLVEKRLARPV
KLQKPLESSVQLHSYFYSTHDMKIGSEELVYITHIDDPWTFYCQLARNANILEQLSCSIT
QLSKVLLNLKTSPLNPGTLCLAKYTDGNWYRGIVIEKEPKKVFFVDFGNIYVVTSDDLLP
IPSDAYDVLLLPMQAVRCSLSDIPDHIPEEVVVWFQETILDKSLKALVVAKDPDGTLIIE
LYGDNIQISASINKKLGLLSYKDRIRKKESEVLCSTTETLEEKNENMKLPCTEYLSKSVG
YKLPNKEILEESYKPQINSSYKELKLLQSLTKTNLVTQYQDSVGNKNSQVFPLTTEKKEE
ISAETPLKTARVEATLSERKIGDSCDKDLPLKFCEFPQKTIMPGFKTTVYVSHINDLSDF
YVQLIEDEAEISHLSERLNSVKTRPEYYVGPPLQRGDMICAVFPEDNLWYRAVIKEQQPN
DLLSVQFIDYGNVSVVHTNKIGRLDLVNAILPGLCIHCSLQGFEVPDNKNSKKMMHYFSQ
RTSEAAIRCEFVKFQDRWEVILADEHGIIADDMISRYALSEKSQVELSTQVIKSASSKSV
NKSDIDTSVFLNWYNPEKKMIRAYATVIDGPEYFWCQFADTEKLQCLEVEVQTAGEQVAD
RRNCIPCPYIGDPCIVRYREDGHYYRALITNICEDYLVSVRLVDFGNIEDCVDPKALWAI
PSELLSVPMQAFPCCLSGFNISEGLCSQEGNDYFYEIITEDVLEITILEIRRDVCDIPLA
IVDLKSKGKSINEKMEKYSKTGIKSALPYENIDSEIKQTLGSYNLDVGLKKLSNKAVQNK
IYMEQQTDELAEITEKDVNIIGTKPSNFRDPKTDNICEGFENPCKDKIDTEELEGELECH
LVDKAEFDDKYLITGFNTLLPHANETKEILELNSLEVPLSPDDESKEFLELESIELQNSL
VVDEEKGELSPVPPNVPLSQECVTKGAMELFTLQLPLSCEAEKQPELELPTAQLPLDDKM
DPLSLGVSQKAQESMCTEDMRKSSCVESFDDQRRMSLHLHGADCDPKTQNEMNICEEEFV
EYKNRDAISALMPLFSEEESSDGSKHNNGLPDHISAQLQNTYTLKAFTVGSKCVVWSSLR
NTWSKCEILETAEEGTRVLNLSNGMEEIVNPENVWNGIPKLDKSPPEKRGLEVMEI
Function
Tudor domain-containing protein involved in germ cell development, more specifically the formation of chromatoid body (during spermiogenesis), Balbiani body (during oogenesis), germ plasm (upon fertilization), and for proper miRNA expression and spliceosome maturation. Essential for RNA-dependent helicase UPF1 localization to chromatoid body, for UPF1-UPF2 and UPF1-DDX4 interactions which are required for mRNA degradation, using the extended 3' UTR-triggered nonsense-mediated mRNA decay (NMD) pathway. Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through interaction with arginine N-methyltransferase PRMT5 and symmetrically arginine dimethylated SNRPB (small nuclear ribonucleoprotein-associated protein).
Reactome Pathway
PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colon cancer DISVC52G Strong Altered Expression [1]
Colon carcinoma DISJYKUO Strong Altered Expression [1]
Male infertility DISY3YZZ Strong Genetic Variation [2]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation DIS56JR8 Moderate Autosomal recessive [3]
Oligospermia DIS6YJF3 Limited Autosomal recessive [4]
Schizophrenia DISSRV2N Limited Autosomal dominant [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 6 (TDRD6). [5]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Tudor domain-containing protein 6 (TDRD6). [9]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Tudor domain-containing protein 6 (TDRD6). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Tudor domain-containing protein 6 (TDRD6). [7]
Malathion DMXZ84M Approved Malathion increases the expression of Tudor domain-containing protein 6 (TDRD6). [8]
Permethrin DMZ0Q1G Approved Permethrin increases the expression of Tudor domain-containing protein 6 (TDRD6). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Tudor domain-containing protein 6 (TDRD6). [6]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Tudor domain-containing protein 6 (TDRD6). [10]
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⏷ Show the Full List of 6 Drug(s)

References

1 Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets.Cancer Res. 2002 Jul 15;62(14):4041-7.
2 TDRD6 is associated with oligoasthenoteratozoospermia by sequencing the patient from a consanguineous family.Gene. 2018 Jun 15;659:84-88. doi: 10.1016/j.gene.2018.03.040. Epub 2018 Mar 15.
3 A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
4 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
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 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
7 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
8 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.
9 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.
10 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.