Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQLZ6Z7)

• DOT Name: Striatin-interacting protein 2 (STRIP2)
• Synonyms: Protein FAM40B
• Gene Name: STRIP2
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Advanced cancer
  Tourette syndrome
• UniProt ID: STRP2_HUMAN
• Pfam ID: PF11882 ; PF07923
• Sequence:
  MEDPAAPGTGGPPANGNGNGGGKGKQAAPKGREAFRSQRRESEGSVDCPTLEFEYGDADG
  HAAELSELYSYTENLEFTNNRRCFEEDFKTQVQGKEWLELEEDAQKAYIMGLLDRLEVVS
  RERRLKVARAVLYLAQGTFGECDSEVDVLHWSRYNCFLLYQMGTFSTFLELLHMEIDNSQ
  ACSSALRKPAVSIADSTELRVLLSVMYLMVENIRLERETDPCGWRTARETFRTELSFSMH
  NEEPFALLLFSMVTKFCSGLAPHFPIKKVLLLLWKVVMFTLGGFEHLQTLKVQKRAELGL
  PPLAEDSIQVVKSMRAASPPSYTLDLGESQLAPPPSKLRGRRGSRRQLLTKQDSLDIYNE
  RDLFKTEEPATEEEEESAGDGERTLDGELDLLEQDPLVPPPPSQAPLSAERVAFPKGLPW
  APKVRQKDIEHFLEMSRNKFIGFTLGQDTDTLVGLPRPIHESVKTLKQHKYISIADVQIK
  NEEELEKCPMSLGEEVVPETPCEILYQGMLYSLPQYMIALLKILLAAAPTSKAKTDSINI
  LADVLPEEMPITVLQSMKLGIDVNRHKEIIVKSISTLLLLLLKHFKLNHIYQFEYVSQHL
  VFANCIPLILKFFNQNILSYITAKNSISVLDYPCCTIQDLPELTTESLEAGDNSQFCWRN
  LFSCINLLRLLNKLTKWKHSRTMMLVVFKSAPILKRALKVKQAMLQLYVLKLLKLQTKYL
  GRQWRKSNMKTMSAIYQKVRHRMNDDWAYGNDIDARPWDFQAEECTLRANIEAFNSRRYD
  RPQDSEFSPVDNCLQSVLGQRLDLPEDFHYSYELWLEREVFSQPICWEELLQNH
• Function: Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[2]
Tourette syndrome	DISX9D54	No Known	Unknown	[3]

14 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-interacting protein 2 (STRIP2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Striatin-interacting protein 2 (STRIP2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Striatin-interacting protein 2 (STRIP2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Striatin-interacting protein 2 (STRIP2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Striatin-interacting protein 2 (STRIP2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Striatin-interacting protein 2 (STRIP2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Striatin-interacting protein 2 (STRIP2).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Striatin-interacting protein 2 (STRIP2).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Striatin-interacting protein 2 (STRIP2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Striatin-interacting protein 2 (STRIP2).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Striatin-interacting protein 2 (STRIP2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Striatin-interacting protein 2 (STRIP2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Striatin-interacting protein 2 (STRIP2).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Striatin-interacting protein 2 (STRIP2).	[18]

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-interacting protein 2 (STRIP2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Striatin-interacting protein 2 (STRIP2).	[16]

References

• [1] STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38-AKT-MMP-2 signaling pathway.J Cell Physiol. 2019 Dec;234(12):22463-22476. doi: 10.1002/jcp.28810. Epub 2019 May 15.
• [2] STRIPAK components determine mode of cancer cell migration and metastasis.Nat Cell Biol. 2015 Jan;17(1):68-80. doi: 10.1038/ncb3083. Epub 2014 Dec 22.
• [3] Identification of candidate genes involved in the etiology of sporadic Tourette syndrome by exome sequencing. Am J Med Genet B Neuropsychiatr Genet. 2017 Oct;174(7):712-723. doi: 10.1002/ajmg.b.32559. Epub 2017 Jun 13.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [10] 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.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.