Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NSZJ1)

• DOT Name: HCLS1-binding protein 3 (HS1BP3)
• Synonyms: HS1-binding protein 3; HSP1BP-3
• Gene Name: HS1BP3
• Related Disease:
  Cardiovascular disease
  Young-onset Parkinson disease
• UniProt ID: H1BP3_HUMAN
• Pfam ID: PF00787
• Sequence:
  MQSPAVLVTSRRLQNAHTGLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHRPE
  DVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLFVGESDIRERRAVFNEILRCVS
  KDAELAGSPELLEFLGTRSPGAAGLTSRDSSVLDGTDSQTGNDEEAFDFFEEQDQVAEEG
  PPVQSLKGEDAEESLEEEEALDPLGIMRSKKPKKHPKVAVKAKPSPRLTIFDEEVDPDEG
  LFGPGRKLSPQDPSEDVSSVDPLKLFDDPDLGGAIPLGDSLLLPAACESGGPTPSLSHRD
  ASKELFRVEEDLDQILNLGAEPKPKPQLKPKPPVAAKPVIPRKPAVPPKAGPAEAVAGQQ
  KPQEQIQAMDEMDILQYIQDHDTPAQAAPSLF
• Function: May be a modulator of IL-2 signaling.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Young-onset Parkinson disease	DIS05LFS	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of HCLS1-binding protein 3 (HS1BP3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of HCLS1-binding protein 3 (HS1BP3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of HCLS1-binding protein 3 (HS1BP3).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of HCLS1-binding protein 3 (HS1BP3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of HCLS1-binding protein 3 (HS1BP3).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of HCLS1-binding protein 3 (HS1BP3).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of HCLS1-binding protein 3 (HS1BP3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of HCLS1-binding protein 3 (HS1BP3).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of HCLS1-binding protein 3 (HS1BP3).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of HCLS1-binding protein 3 (HS1BP3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of HCLS1-binding protein 3 (HS1BP3).	[15]

2 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 HCLS1-binding protein 3 (HS1BP3).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of HCLS1-binding protein 3 (HS1BP3).	[14]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] A family with Parkinson disease, essential tremor, bell palsy, and parkin mutations.Arch Neurol. 2007 Mar;64(3):421-4. doi: 10.1001/archneur.64.3.421.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] 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.
• [8] 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.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.