Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT3T7QT)

• DOT Name: Serine-threonine kinase receptor-associated protein (STRAP)
• Synonyms: MAP activator with WD repeats; UNR-interacting protein; WD-40 repeat protein PT-WD
• Gene Name: STRAP
• UniProt ID: STRAP_HUMAN
• Pfam ID: PF00400
• Sequence:
  MAMRQTPLTCSGHTRPVVDLAFSGITPYGYFLISACKDGKPMLRQGDTGDWIGTFLGHKG
  AVWGATLNKDATKAATAAADFTAKVWDAVSGDELMTLAHKHIVKTVDFTQDSNYLLTGGQ
  DKLLRIYDLNKPEAEPKEISGHTSGIKKALWCSEDKQILSADDKTVRLWDHATMTEVKSL
  NFNMSVSSMEYIPEGEILVITYGRSIAFHSAVSLDPIKSFEAPATINSASLHPEKEFLVA
  GGEDFKLYKYDYNSGEELESYKGHFGPIHCVRFSPDGELYASGSEDGTLRLWQTVVGKTY
  GLWKCVLPEEDSGELAKPKIGFPETTEEELEEIASENSDCIFPSAPDVKA
• Function: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein.
• Reactome Pathway: Downregulation of TGF-beta receptor signaling (R-HSA-2173788)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Serine-threonine kinase receptor-associated protein (STRAP) affects the response to substance of Josamycin.	[15]

13 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 Serine-threonine kinase receptor-associated protein (STRAP).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[9]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[10]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Serine-threonine kinase receptor-associated protein (STRAP).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Serine-threonine kinase receptor-associated protein (STRAP).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine-threonine kinase receptor-associated protein (STRAP).	[12]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [7] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways. Int J Mol Sci. 2019 Nov 30;20(23):6039. doi: 10.3390/ijms20236039.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [12] 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.
• [13] 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.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [15] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.