Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO7UVK7)

• DOT Name: Splicing factor Cactin (CACTIN)
• Synonyms: Renal carcinoma antigen NY-REN-24
• Gene Name: CACTIN
• UniProt ID: CATIN_HUMAN
• PDB ID: 6QDV; 7W5A; 7W5B; 8C6J
• Pfam ID: PF10312 ; PF09732
• Sequence:
  MGRDTRSRSRSAGRRGRRRQSQSGSRSRSRSHGRRNRRRREDEGRRRRRRRSRERRSDSE
  EERWQRSGMRSRSPPRPKWHSRDGSSQSDSGEEQSRGQWARRRRRARSWSPSSSASSSAS
  PGRSQSPRAAAAALSQQQSLQERLRLREERKQQEELMKAFETPEEKRARRLAKKEAKERK
  KREKMGWGEEYMGYTNTDNPFGDNNLLGTFIWNKALEKKGISHLEEKELKERNKRIQEDN
  RLELQKVKQLRLEREREKAMREQELEMLQREKEAEHFKTWEEQEDNFHLQQAKLRSKIRI
  RDGRAKPIDLLAKYISAEDDDLAVEMHEPYTFLNGLTVADMEDLLEDIQVYMELEQGKNA
  DFWRDMTTITEDEISKLRKLEASGKGPGERREGVNASVSSDVQSVFKGKTYNQLQVIFQG
  IEGKIRAGGPNLDMGYWESLLQQLRAHMARARLRERHQDVLRQKLYKLKQEQGVESEPLF
  PILKQEPQSPSRSLEPEDAAPTPPGPSSEGGPAEAEVDGATPTEGDGDGDGEGEGEGEAV
  LMEEDLIQQSLDDYDAGRYSPRLLTAHELPLDAHVLEPDEDLQRLQLSRQQLQVTGDASE
  SAEDIFFRRAKEGMGQDEAQFSVEMPLTGKAYLWADKYRPRKPRFFNRVHTGFEWNKYNQ
  THYDFDNPPPKIVQGYKFNIFYPDLIDKRSTPEYFLEACADNKDFAILRFHAGPPYEDIA
  FKIVNREWEYSHRHGFRCQFANGIFQLWFHFKRYRYRR
• Function: Plays a role in pre-mRNA splicing by facilitating excision of a subset of introns. Required for the splicing of CDCA5/Sororin, a regulator of sister chromatid cohesion. Involved in the regulation of innate immune response. Acts as a negative regulator of Toll-like receptor, interferon-regulatory factor (IRF) and canonical NF-kappa-B signaling pathways. Contributes to the regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous pro-inflammatory stimuli.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

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 Splicing factor Cactin (CACTIN).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Splicing factor Cactin (CACTIN).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Splicing factor Cactin (CACTIN).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Splicing factor Cactin (CACTIN).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Splicing factor Cactin (CACTIN).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Splicing factor Cactin (CACTIN).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Splicing factor Cactin (CACTIN).	[6]

References

• [1] 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.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.