Details of Drug Off-Target (DOT)

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

• DOT Name: SH3 domain-containing YSC84-like protein 1 (SH3YL1)
• Gene Name: SH3YL1
• Related Disease:
  Mantle cell lymphoma
  Multiple sclerosis
• UniProt ID: SH3Y1_HUMAN
• PDB ID: 2D8H
• Pfam ID: PF14604 ; PF04366
• Sequence:
  MNNPIPSNLKSEAKKAAKILREFTEITSRNGPDKIIPAHVIAKAKGLAILSVIKAGFLVT
  ARGGSGIVVARLPDGKWSAPSAIGIAGLGGGFEIGIEVSDLVIILNYDRAVEAFAKGGNL
  TLGGNLTVAVGPLGRNLEGNVALRSSAAVFTYCKSRGLFAGVSLEGSCLIERKETNRKFY
  CQDIRAYDILFGDTPRPAQAEDLYEILDSFTEKYENEGQRINARKAAREQRKSSAKELPP
  KPLSRPQQSSAPVQLNSGSQSNRNEYKLYPGLSSYHERVGNLNQPIEVTALYSFEGQQPG
  DLNFQAGDRITVISKTDSHFDWWEGKLRGQTGIFPANYVTMN

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Strong	Posttranslational Modification	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[13]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of SH3 domain-containing YSC84-like protein 1 (SH3YL1).	[18]

References

• [1] Health-related quality of life data from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma treated with ibrutinib versus temsirolimus.Leuk Lymphoma. 2017 Dec;58(12):2824-2832. doi: 10.1080/10428194.2017.1326034. Epub 2017 May 30.
• [2] Non-parametric combination analysis of multiple data types enables detection of novel regulatory mechanisms in T cells of multiple sclerosis patients.Sci Rep. 2019 Aug 19;9(1):11996. doi: 10.1038/s41598-019-48493-7.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] 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.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.