Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHK2ZN6)

• DOT Name: Striatin-4 (STRN4)
• Synonyms: Zinedin
• Gene Name: STRN4
• Related Disease:
  Autism
  Non-small-cell lung cancer
  Prostate neoplasm
  Advanced cancer
  Neoplasm
  Pancreatic cancer
  Nervous system disease
• UniProt ID: STRN4_HUMAN
• Pfam ID: PF08232 ; PF00400
• Sequence:
  MMEERAAAAVAAAASSCRPLGSGAGPGPTGAAPVSAPAPGPGPAGKGGGGGGSPGPTAGP
  EPLSLPGILHFIQHEWARFEAEKARWEAERAELQAQVAFLQGERKGQENLKTDLVRRIKM
  LEYALKQERAKYHKLKFGTDLNQGEKKADVSEQVSNGPVESVTLENSPLVWKEGRQLLRQ
  YLEEVGYTDTILDMRSKRVRSLLGRSLELNGAVEPSEGAPRAPPGPAGLSGGESLLVKQI
  EEQIKRNAAGKDGKERLGGSVLGQIPFLQNCEDEDSDEDDELDSVQHKKQRVKLPSKALV
  PEMEDEDEEDDSEDAINEFDFLGSGEDGEGAPDPRRCTVDGSPHELESRRVKLQGILADL
  RDVDGLPPKVTGPPPGTPQPRPHEDVFIMDTIGGGEVSLGDLADLTVTNDNDLSCDLSDS
  KDAFKKTWNPKFTLRSHYDGIRSLAFHHSQSALLTASEDGTLKLWNLQKAVTAKKNAALD
  VEPIHAFRAHRGPVLAVAMGSNSEYCYSGGADACIHSWKIPDLSMDPYDGYDPSVLSHVL
  EGHGDAVWGLAFSPTSQRLASCSADGTVRIWDPSSSSPACLCTFPTASEHGVPTSVAFTS
  TEPAHIVASFRSGDTVLYDMEVGSALLTLESRGSSGPTQINQVVSHPNQPLTITAHDDRG
  IRFLDNRTGKPVHSMVAHLDAVTCLAVDPNGAFLMSGSHDCSLRLWSLDNKTCVQEITAH
  RKKHEEAIHAVACHPSKALIASAGADALAKVFV
• Function: Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Pancreatic cancer	DISJC981	moderate	Biomarker	[4]
Nervous system disease	DISJ7GGT	Disputed	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Striatin-4 (STRN4).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Striatin-4 (STRN4).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Striatin-4 (STRN4).	[8]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Striatin-4 (STRN4).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Striatin-4 (STRN4).	[11]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin decreases the expression of Striatin-4 (STRN4).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Striatin-4 (STRN4).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Striatin-4 (STRN4).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Striatin-4 (STRN4).	[13]

References

• [1] Determination of dendritic spine morphology by the striatin scaffold protein STRN4 through interaction with the phosphatase PP2A.J Biol Chem. 2017 Jun 9;292(23):9451-9464. doi: 10.1074/jbc.M116.772442. Epub 2017 Apr 25.
• [2] miR-29b inhibits non-small cell lung cancer progression by targeting STRN4.Hum Cell. 2020 Jan;33(1):220-231. doi: 10.1007/s13577-019-00305-w. Epub 2019 Dec 7.
• [3] Pro-oncogene Pokemon Promotes Prostate Cancer Progression by Inducing STRN4 Expression.J Cancer. 2019 Apr 21;10(8):1833-1845. doi: 10.7150/jca.29471. eCollection 2019.
• [4] Silencing of STRN4 suppresses the malignant characteristics of cancer cells.Cancer Sci. 2014 Dec;105(12):1526-32. doi: 10.1111/cas.12541. Epub 2014 Oct 23.
• [5] Whole Genome Expression Analysis in a Mouse Model of Tauopathy Identifies MECP2 as a Possible Regulator of Tau Pathology.Front Mol Neurosci. 2017 Mar 17;10:69. doi: 10.3389/fnmol.2017.00069. eCollection 2017.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [11] 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.
• [12] RNA-binding proteins and heat-shock protein 90 are constituents of the cytoplasmic capping enzyme interactome. J Biol Chem. 2018 Oct 26;293(43):16596-16607. doi: 10.1074/jbc.RA118.004973. Epub 2018 Aug 30.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.