Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRS37HK)

• DOT Name: Hsp70-binding protein 1 (HSPBP1)
• Synonyms: HspBP1; Heat shock protein-binding protein 1; Hsp70-binding protein 2; HspBP2; Hsp70-interacting protein 1; Hsp70-interacting protein 2
• Gene Name: HSPBP1
• Related Disease:
  Brain neoplasm
  Breast neoplasm
  HIV infectious disease
  Lung neoplasm
  Fetal growth restriction
  Neoplasm
  Rheumatoid arthritis
  Spinocerebellar ataxia type 3
• UniProt ID: HPBP1_HUMAN
• PDB ID: 1XQR; 1XQS; 8X87
• Pfam ID: PF08609
• Sequence:
  MSDEGSRGSRLPLALPPASQGCSSGGGGGGSSAGGSGNSRPPRNLQGLLQMAITAGSEEP
  DPPPEPMSEERRQWLQEAMSAAFRGQREEVEQMKSCLRVLSQPMPPTAGEAEQAADQQER
  EGALELLADLCENMDNAADFCQLSGMHLLVGRYLEAGAAGLRWRAAQLIGTCSQNVAAIQ
  EQVLGLGALRKLLRLLDRDACDTVRVKALFAISCLVREQEAGLLQFLRLDGFSVLMRAMQ
  QQVQKLKVKSAFLLQNLLVGHPEHKGTLCSMGMVQQLVALVRTEHSPFHEHVLGALCSLV
  TDFPQGVRECREPELGLEELLRHRCQLLQQHEEYQEELEFCEKLLQTCFSSPADDSMDR
• Function: Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain neoplasm	DISY3EKS	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
HIV infectious disease	DISO97HC	Strong	Biomarker	[3]
Lung neoplasm	DISVARNB	Strong	Biomarker	[4]
Fetal growth restriction	DIS5WEJ5	moderate	Biomarker	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[6]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Biomarker	[7]

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 Hsp70-binding protein 1 (HSPBP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hsp70-binding protein 1 (HSPBP1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Hsp70-binding protein 1 (HSPBP1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hsp70-binding protein 1 (HSPBP1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hsp70-binding protein 1 (HSPBP1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hsp70-binding protein 1 (HSPBP1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hsp70-binding protein 1 (HSPBP1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Hsp70-binding protein 1 (HSPBP1).	[15]

References

• [1] Heat shock protein 70-binding protein 1 is highly expressed in high-grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces.Cancer Sci. 2009 Oct;100(10):1870-9. doi: 10.1111/j.1349-7006.2009.01269.x. Epub 2009 Jul 1.
• [2] HspBP1 levels are elevated in breast tumor tissue and inversely related to tumor aggressiveness.Cell Stress Chaperones. 2009 May;14(3):301-10. doi: 10.1007/s12192-008-0085-6. Epub 2008 Nov 6.
• [3] HspBP1 and anti-HspBP1 levels in the serum of HIV-infected individuals are associated to the disease progression.J Appl Microbiol. 2019 Aug;127(2):576-585. doi: 10.1111/jam.14230. Epub 2019 Jun 7.
• [4] [Co-detection of P21, P53 and HSP70 and their possible role in diagnosis of polycyclic aromatic hydrocarbons (PAHs)-related lung cancer].Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003 Oct;21(5):359-61.
• [5] Assessment of placental and maternal stress responses in patients with pregnancy related complications via monitoring of heat shock protein mRNA levels.Mol Biol Rep. 2015 Mar;42(3):625-37. doi: 10.1007/s11033-014-3808-z. Epub 2014 Oct 31.
• [6] Heat shock protein gene expression profile may differentiate between rheumatoid arthritis, osteoarthritis, and healthy controls.Scand J Rheumatol. 2011;40(5):354-7. doi: 10.3109/03009742.2011.552522. Epub 2011 Mar 21.
• [7] Carboxyl Terminus of Hsp70-Interacting Protein Is Increased in Serum and Cerebrospinal Fluid of Patients With Spinocerebellar Ataxia Type 3.Front Neurol. 2019 Oct 15;10:1094. doi: 10.3389/fneur.2019.01094. eCollection 2019.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.