Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYXMC4G)

• DOT Name: Heat shock 70 kDa protein 13 (HSPA13)
• Synonyms: Microsomal stress-70 protein ATPase core; Stress-70 protein chaperone microsome-associated 60 kDa protein
• Gene Name: HSPA13
• Related Disease:
  Gastric cancer
  Prion disease
  Stomach cancer
  Gastric neoplasm
• UniProt ID: HSP13_HUMAN
• Pfam ID: PF00012
• Sequence:
  MAREMTILGSAVLTLLLAGYLAQQYLPLPTPKVIGIDLGTTYCSVGVFFPGTGKVKVIPD
  ENGHISIPSMVSFTDNDVYVGYESVELADSNPQNTIYDAKRFIGKIFTAEELEAEIGRYP
  FKVLNKNGMVEFSVTSNETITVSPEYVGSRLLLKLKEMAEAYLGMPVANAVISVPAEFDL
  KQRNSTIEAANLAGLKILRVINEPTAAAMAYGLHKADVFHVLVIDLGGGTLDVSLLNKQG
  GMFLTRAMSGNNKLGGQDFNQRLLQYLYKQIYQTYGFVPSRKEEIHRLRQAVEMVKLNLT
  LHQSAQLSVLLTVEEQDRKEPHSSDTELPKDKLSSADDHRVNSGFGRGLSDKKSGESQVL
  FETEISRKLFDTLNEDLFQKILVPIQQVLKEGHLEKTEIDEVVLVGGSTRIPRIRQVIQE
  FFGKDPNTSVDPDLAVVTGVAIQAGIDGGSWPLQVSALEIPNKHLQKTNFN
• Function: Has peptide-independent ATPase activity.
• Tissue Specificity: Constitutively expressed in all tissues.
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[1]
Prion disease	DISOUMB0	Strong	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[1]
Gastric neoplasm	DISOKN4Y	Disputed	Biomarker	[3]

23 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 Heat shock 70 kDa protein 13 (HSPA13).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Heat shock 70 kDa protein 13 (HSPA13).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Heat shock 70 kDa protein 13 (HSPA13).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[14]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[19]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Heat shock 70 kDa protein 13 (HSPA13).	[25]

References

• [1] Stomach cancer-derived del223V-226L mutation of the STCH gene causes loss of sensitization to TRAIL-mediated apoptosis.Biochem Biophys Res Commun. 2008 Nov 21;376(3):499-503. doi: 10.1016/j.bbrc.2008.09.013. Epub 2008 Sep 13.
• [2] Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice.Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13722-7. doi: 10.1073/pnas.1208917109. Epub 2012 Aug 6.
• [3] A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.Biochem Biophys Res Commun. 2005 Sep 23;335(2):566-74. doi: 10.1016/j.bbrc.2005.07.110.
• [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] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] 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.
• [10] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [11] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [14] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [15] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [18] Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
• [19] 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.
• [20] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [21] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [22] 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.
• [23] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.