Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCJ4CVE)

• DOT Name: Striatin-interacting protein 1 (STRIP1)
• Synonyms: Protein FAM40A
• Gene Name: STRIP1
• Related Disease: Focal segmental glomerulosclerosis
• UniProt ID: STRP1_HUMAN
• PDB ID: 7K36
• Pfam ID: PF11882 ; PF07923
• Sequence:
  MEPAVGGPGPLIVNNKQPQPPPPPPPAAAQPPPGAPRAAAGLLPGGKAREFNRNQRKDSE
  GYSESPDLEFEYADTDKWAAELSELYSYTEGPEFLMNRKCFEEDFRIHVTDKKWTELDTN
  QHRTHAMRLLDGLEVTAREKRLKVARAILYVAQGTFGECSSEAEVQSWMRYNIFLLLEVG
  TFNALVELLNMEIDNSAACSSAVRKPAISLADSTDLRVLLNIMYLIVETVHQECEGDKAE
  WRTMRQTFRAELGSPLYNNEPFAIMLFGMVTKFCSGHAPHFPMKKVLLLLWKTVLCTLGG
  FEELQSMKAEKRSILGLPPLPEDSIKVIRNMRAASPPASASDLIEQQQKRGRREHKALIK
  QDNLDAFNERDPYKADDSREEEEENDDDNSLEGETFPLERDEVMPPPLQHPQTDRLTCPK
  GLPWAPKVREKDIEMFLESSRSKFIGYTLGSDTNTVVGLPRPIHESIKTLKQHKYTSIAE
  VQAQMEEEYLRSPLSGGEEEVEQVPAETLYQGLLPSLPQYMIALLKILLAAAPTSKAKTD
  SINILADVLPEEMPTTVLQSMKLGVDVNRHKEVIVKAISAVLLLLLKHFKLNHVYQFEYM
  AQHLVFANCIPLILKFFNQNIMSYITAKNSISVLDYPHCVVHELPELTAESLEAGDSNQF
  CWRNLFSCINLLRILNKLTKWKHSRTMMLVVFKSAPILKRALKVKQAMMQLYVLKLLKVQ
  TKYLGRQWRKSNMKTMSAIYQKVRHRLNDDWAYGNDLDARPWDFQAEECALRANIERFNA
  RRYDRAHSNPDFLPVDNCLQSVLGQRVDLPEDFQMNYDLWLEREVFSKPISWEELLQ
• Function: Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[1]

6 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-interacting protein 1 (STRIP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Striatin-interacting protein 1 (STRIP1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Striatin-interacting protein 1 (STRIP1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Striatin-interacting protein 1 (STRIP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Striatin-interacting protein 1 (STRIP1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Striatin-interacting protein 1 (STRIP1).	[8]

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-interacting protein 1 (STRIP1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Striatin-interacting protein 1 (STRIP1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Striatin-interacting protein 1 (STRIP1).	[10]

References

• [1] FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin.Arch Med Sci. 2019 Jan;15(1):165-173. doi: 10.5114/aoms.2018.73138. Epub 2018 Feb 2.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.