Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3IKRL2)

• DOT Name: Cleavage stimulation factor subunit 2 tau variant (CSTF2T)
• Synonyms: CF-1 64 kDa subunit tau variant; Cleavage stimulation factor 64 kDa subunit tau variant; CSTF 64 kDa subunit tau variant; TauCstF-64
• Gene Name: CSTF2T
• Related Disease: Male infertility
• UniProt ID: CSTFT_HUMAN
• Pfam ID: PF14327 ; PF14304 ; PF00076
• Sequence:
  MSSLAVRDPAMDRSLRSVFVGNIPYEATEEQLKDIFSEVGSVVSFRLVYDRETGKPKGYG
  FCEYQDQETALSAMRNLNGREFSGRALRVDNAASEKNKEELKSLGPAAPIIDSPYGDPID
  PEDAPESITRAVASLPPEQMFELMKQMKLCVQNSHQEARNMLLQNPQLAYALLQAQVVMR
  IMDPEIALKILHRKIHVTPLIPGKSQSVSVSGPGPGPGPGLCPGPNVLLNQQNPPAPQPQ
  HLARRPVKDIPPLMQTPIQGGIPAPGPIPAAVPGAGPGSLTPGGAMQPQLGMPGVGPVPL
  ERGQVQMSDPRAPIPRGPVTPGGLPPRGLLGDAPNDPRGGTLLSVTGEVEPRGYLGPPHQ
  GPPMHHASGHDTRGPSSHEMRGGPLGDPRLLIGEPRGPMIDQRGLPMDGRGGRDSRAMET
  RAMETEVLETRVMERRGMETCAMETRGMEARGMDARGLEMRGPVPSSRGPMTGGIQGPGP
  INIGAGGPPQGPRQVPGISGVGNPGAGMQGTGIQGTGMQGAGIQGGGMQGAGIQGVSIQG
  GGIQGGGIQGASKQGGSQPSSFSPGQSQVTPQDQEKAALIMQVLQLTADQIAMLPPEQRQ
  SILILKEQIQKSTGAS
• Function: May play a significant role in AAUAAA-independent mRNA polyadenylation in germ cells. Directly involved in the binding to pre-mRNAs.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Processing of Intronless Pre-mRNAs (R-HSA-77595)
  mRNA 3'-end processing (R-HSA-72187)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Cleavage stimulation factor subunit 2 tau variant (CSTF2T) affects the response to substance of Topotecan.	[14]

12 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 Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[9]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cleavage stimulation factor subunit 2 tau variant (CSTF2T).	[13]

References

• [1] Cstf2t Regulates expression of histones and histone-like proteins in male germ cells.Andrology. 2018 Jul;6(4):605-615. doi: 10.1111/andr.12488. Epub 2018 Apr 19.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.
• [14] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.