Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLOZL5I)

• DOT Name: Striatin (STRN)
• Gene Name: STRN
• Related Disease:
  Neoplasm
  Thyroid gland papillary carcinoma
  Arrhythmogenic right ventricular cardiomyopathy
  Bladder cancer
  Cardiac failure
  Cardiomyopathy
  Colorectal carcinoma
  Congestive heart failure
  Familial adenomatous polyposis
  Renal cell carcinoma
  Schizophrenia
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Urinary bladder cancer
  Urinary bladder neoplasm
  Thyroid gland undifferentiated (anaplastic) carcinoma
• UniProt ID: STRN_HUMAN
• Pfam ID: PF08232 ; PF00400
• Sequence:
  MDEQAGPGVFFSNNHPGAGGAKGLGPLAEAAAAGDGAAAAGAARAQYSLPGILHFLQHEW
  ARFEVERAQWEVERAELQAQIAFLQGERKGQENLKKDLVRRIKMLEYALKQERAKYHKLK
  YGTELNQGDMKPPSYDSDEGNETEVQPQQNSQLMWKQGRQLLRQYLQEVGYTDTILDVKS
  KRVRALLGFSSDVTDREDDKNQDSVVNGTEAEVKETAMIAKSELTDSASVLDNFKFLESA
  AADFSDEDEDDDVDGREKSVIDTSTIVRKKALPDSGEDRDTKEALKEFDFLVTSEEGDNE
  SRSAGDGTDWEKEDQCLMPEAWNVDQGVITKLKEQYKKERKGKKGVKRPNRSKLQDMLAN
  LRDVDELPSLQPSVGSPSRPSSSRLPEHEINRADEVEALTFPPSSGKSFIMGADEALESE
  LGLGELAGLTVANEADSLTYDIANNKDALRKTWNPKFTLRSHFDGIRALAFHPIEPVLIT
  ASEDHTLKMWNLQKTAPAKKSTSLDVEPIYTFRAHKGPVLCVVMSSNGEQCYSGGTDGLI
  QGWNTTNPNIDPYDSYDPSVLRGPLLGHTDAVWGLAYSAAHQRLLSCSADGTLRLWNTTE
  VAPALSVFNDTKELGIPASVDLVSSDPSHMVASFSKGYTSIFNMETQQRILTLESNVDTT
  ANSSCQINRVISHPTLPISITAHEDRHIKFYDNNTGKLIHSMVAHLEAVTSLAVDPNGLY
  LMSGSHDCSIRLWNLESKTCIQEFTAHRKKFEESIHDVAFHPSKCYIASAGADALAKVFV
• Function: Calmodulin-binding protein which may function as scaffolding or signaling protein and may play a role in dendritic Ca(2+) signaling.
• Tissue Specificity: Preferentially expressed in brain.
• Reactome Pathway:
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Signaling by cytosolic PDGFRA and PDGFRB fusion proteins (R-HSA-9673766)
  ALK mutants bind TKIs (R-HSA-9700645)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Genetic Variation	[2]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Strong	Genetic Variation	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[5]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[7]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[8]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[9]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[10]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[10]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[10]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Striatin (STRN) affects the response to substance of Vinblastine.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Striatin (STRN).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Striatin (STRN).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Striatin (STRN).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Striatin (STRN).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Striatin (STRN).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Striatin (STRN).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Striatin (STRN).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Striatin (STRN).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Striatin (STRN).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Striatin (STRN).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Striatin (STRN).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Striatin (STRN).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Striatin (STRN).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Striatin (STRN).	[23]

References

• [1] Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer.Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4233-8. doi: 10.1073/pnas.1321937111. Epub 2014 Feb 3.
• [2] ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population.Eur J Endocrinol. 2018 Jan;178(1):83-91. doi: 10.1530/EJE-17-0499. Epub 2017 Oct 18.
• [3] Genome-wide association identifies a deletion in the 3' untranslated region of striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy.Hum Genet. 2010 Sep;128(3):315-24. doi: 10.1007/s00439-010-0855-y. Epub 2010 Jul 2.
• [4] 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.
• [5] The SLMAP/Striatin complex: An emerging regulator of normal and abnormal cardiac excitation-contraction coupling.Eur J Pharmacol. 2019 Sep 5;858:172491. doi: 10.1016/j.ejphar.2019.172491. Epub 2019 Jun 21.
• [6] Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer.Br J Cancer. 2018 Jul;119(2):230-240. doi: 10.1038/s41416-018-0153-3. Epub 2018 Jun 29.
• [7] Striatin is a novel modulator of cell adhesion.FASEB J. 2019 Apr;33(4):4729-4740. doi: 10.1096/fj.201801882R. Epub 2018 Dec 28.
• [8] Clinicopathologic and Molecular Pathology of Collecting Duct Carcinoma and Related Renal Cell Carcinomas.Adv Anat Pathol. 2017 Mar;24(2):65-77. doi: 10.1097/PAP.0000000000000138.
• [9] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [10] Mouse Model of Poorly Differentiated Thyroid Carcinoma Driven by STRN-ALK Fusion.Am J Pathol. 2018 Nov;188(11):2653-2661. doi: 10.1016/j.ajpath.2018.07.012. Epub 2018 Aug 18.
• [11] 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.
• [12] 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.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [15] 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.
• [16] 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.
• [17] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] 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.
• [22] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [23] 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.
• [24] 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.