Details of Drug Off-Target (DOT)

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

• DOT Name: Heat shock protein beta-6 (HSPB6)
• Synonyms: HspB6; Heat shock 20 kDa-like protein p20
• Gene Name: HSPB6
• Related Disease:
  Cognitive impairment
  Advanced cancer
  Alzheimer disease
  Asthma
  Cardiomyopathy
  Colorectal carcinoma
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Epilepsy
  Hepatocellular carcinoma
  Herpes simplex infection
  Multiple sclerosis
  Myocardial infarction
  Myocardial ischemia
  Neuroblastoma
  Cardiac disease
  Subarachnoid hemorrhage
  Human papillomavirus infection
• UniProt ID: HSPB6_HUMAN
• PDB ID: 4JUS; 4JUT; 5LTW; 5LU1; 5LU2; 5LUM; 5OK9; 5OKF
• Pfam ID: PF00525 ; PF00011
• Sequence:
  MEIPVPVQPSWLRRASAPLPGLSAPGRLFDQRFGEGLLEAELAALCPTTLAPYYLRAPSV
  ALPVAQVPTDPGHFSVLLDVKHFSPEEIAVKVVGEHVEVHARHEERPDEHGFVAREFHRR
  YRLPPGVDPAAVTSALSPEGVLSIQAAPASAQAPPPAAAK
• Function: Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Seems to have versatile functions in various biological processes. Plays a role in regulating muscle function such as smooth muscle vasorelaxation and cardiac myocyte contractility. May regulate myocardial angiogenesis implicating KDR. Overexpression mediates cardioprotection and angiogenesis after induced damage. Stabilizes monomeric YWHAZ thereby supporting YWHAZ chaperone-like activity.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[4]
Epilepsy	DISBB28L	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[7]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[8]
Myocardial infarction	DIS655KI	Strong	Biomarker	[9]
Myocardial ischemia	DISFTVXF	Strong	Posttranslational Modification	[10]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[3]
Cardiac disease	DISVO1I5	moderate	Biomarker	[11]
Subarachnoid hemorrhage	DISI7I8Y	Disputed	Biomarker	[12]
Human papillomavirus infection	DISX61LX	Limited	Biomarker	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock protein beta-6 (HSPB6).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heat shock protein beta-6 (HSPB6).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heat shock protein beta-6 (HSPB6).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Heat shock protein beta-6 (HSPB6).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heat shock protein beta-6 (HSPB6).	[19]

1 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 Heat shock protein beta-6 (HSPB6).	[17]

References

• [1] Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis.Mol Neurobiol. 2018 Nov;55(11):8602-8611. doi: 10.1007/s12035-018-1011-2. Epub 2018 Mar 25.
• [2] Decreased expression of heat shock protein 20 in colorectal cancer and its implication in tumorigenesis.J Cell Biochem. 2015 Feb;116(2):277-86. doi: 10.1002/jcb.24966.
• [3] The phosphorylation of Hsp20 enhances its association with amyloid- to increase protection against neuronal cell death.Mol Cell Neurosci. 2014 Jul;61:46-55. doi: 10.1016/j.mcn.2014.05.002. Epub 2014 May 20.
• [4] Regulation of BECN1-mediated autophagy by HSPB6: Insights from a human HSPB6(S10F) mutant.Autophagy. 2018;14(1):80-97. doi: 10.1080/15548627.2017.1392420. Epub 2018 Jan 29.
• [5] Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway.Cell Mol Neurobiol. 2019 Jan;39(1):111-122. doi: 10.1007/s10571-018-0637-y. Epub 2018 Dec 3.
• [6] VEGF Overexpression Predicts Poor Survival in Hepatocellular Carcinoma.Open Med (Wars). 2017 Dec 9;12:430-439. doi: 10.1515/med-2017-0061. eCollection 2017.
• [7] In Vitro Anti-Viral Effects of Small Heat Shock Proteins 20 and 27: A Novel Therapeutic Approach.Curr Pharm Biotechnol. 2019;20(12):1011-1017. doi: 10.2174/1389201020666190729104648.
• [8] Heat shock proteins are differentially expressed in brain and spinal cord: implications for multiple sclerosis.Clin Exp Immunol. 2018 Nov;194(2):137-152. doi: 10.1111/cei.13186. Epub 2018 Sep 19.
• [9] HSP20-mediated cardiomyocyte exosomes improve cardiac function in mice with myocardial infarction by activating Akt signaling pathway.Eur Rev Med Pharmacol Sci. 2019 Jun;23(11):4873-4881. doi: 10.26355/eurrev_201906_18075.
• [10] Blockade of Hsp20 phosphorylation exacerbates cardiac ischemia/reperfusion injury by suppressed autophagy and increased cell death.Circ Res. 2009 Dec 4;105(12):1223-31. doi: 10.1161/CIRCRESAHA.109.200378. Epub 2009 Oct 22.
• [11] Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure.J Mol Cell Cardiol. 2011 Oct;51(4):574-7. doi: 10.1016/j.yjmcc.2010.09.013. Epub 2010 Sep 30.
• [12] The role and therapeutic potential of heat shock proteins in haemorrhagic stroke.J Cell Mol Med. 2019 Sep;23(9):5846-5858. doi: 10.1111/jcmm.14479. Epub 2019 Jul 5.
• [13] Significance of serum antibodies against HPV E7, Hsp27, Hsp20 and Hp91 in Iranian HPV-exposed women.BMC Infect Dis. 2019 Feb 12;19(1):142. doi: 10.1186/s12879-019-3780-2.
• [14] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [15] 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.
• [16] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [17] 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.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.