Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT44KXPY)

• DOT Name: Striatin-3 (STRN3)
• Synonyms: Cell cycle autoantigen SG2NA; S/G2 antigen
• Gene Name: STRN3
• Related Disease:
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Vitiligo
• UniProt ID: STRN3_HUMAN
• PDB ID: 4N6J; 6AKL; 6IUR; 7K36
• Pfam ID: PF08232 ; PF00400
• Sequence:
  MDELAGGGGGGPGMAAPPRQQQGPGGNLGLSPGGNGAAGGGGPPASEGAGPAAGPELSRP
  QQYTIPGILHYIQHEWARFEMERAHWEVERAELQARIAFLQGERKGQENLKKDLVRRIKM
  LEYALKQERAKYHKLKYGTELNQGDLKMPTFESEETKDTEAPTAPQNSQLTWKQGRQLLR
  QYLQEVGYTDTILDVRSQRVRSLLGLSNSEPNGSVETKNLEQILNGGESPKQKGQEIKRS
  SGDVLETFNFLENADDSDEDEENDMIEGIPEGKDKHRMNKHKIGNEGLAADLTDDPDTEE
  ALKEFDFLVTAEDGEGAGEARSSGDGTEWDKDDLSPTAEVWDVDQGLISKLKEQYKKERK
  GKKGVKRANRTKLYDMIADLGDDELPHIPSGIINQSRSASTRMTDHEGARAEEAEPITFP
  SGGGKSFIMGSDDVLLSVLGLGDLADLTVTNDADYSYDLPANKDAFRKTWNPKYTLRSHF
  DGVRALAFHPVEPVLVTASEDHTLKLWNLQKTVPAKKSASLDVEPIYTFRAHIGPVLSLA
  ISSNGEQCFSGGIDATIQWWNMPSPSVDPYDTYEPNVLAGTLVGHTDAVWGLAYSGIKNQ
  LLSCSADGTVRLWNPQEKLPCICTYNGDKKHGIPTSVDFIGCDPAHMVTSFNTGSAVIYD
  LETSQSLVILSSQVDSGLQSNNHINRVVSHPTLPVTITAHEDRHIKFFDNKTGKMIHSMV
  AHLDAVTSLAVDPNGIYLMSGSHDCSIRLWNLDSKTCVQEITAHRKKLDESIYDVAFHSS
  KAYIASAGADALAKVFV
• Function: Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Vitiligo	DISR05SL	Strong	Genetic Variation	[2]

11 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 Striatin-3 (STRN3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Striatin-3 (STRN3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Striatin-3 (STRN3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Striatin-3 (STRN3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Striatin-3 (STRN3).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Striatin-3 (STRN3).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Striatin-3 (STRN3).	[9]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Striatin-3 (STRN3).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Striatin-3 (STRN3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Striatin-3 (STRN3).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Striatin-3 (STRN3).	[7]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Striatin-3 (STRN3).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Striatin-3 (STRN3).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Striatin-3 (STRN3).	[13]

References

• [1] Biophysical Characterization of SG2NA Variants and their Interaction with DJ-1 and Calmodulin in vitro.Cell Biochem Biophys. 2018 Dec;76(4):451-461. doi: 10.1007/s12013-018-0854-5. Epub 2018 Aug 21.
• [2] Three new single nucleotide polymorphisms identified by a genome-wide association study in Korean patients with vitiligo.J Korean Med Sci. 2013 May;28(5):775-9. doi: 10.3346/jkms.2013.28.5.775. Epub 2013 May 2.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.