Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTS1YNP)

• DOT Name: Tapasin-related protein (TAPBPL)
• Synonyms: TAPASIN-R; TAP-binding protein-like; TAP-binding protein-related protein; TAPBP-R; Tapasin-like
• Gene Name: TAPBPL
• Related Disease:
  Alzheimer disease
  Neoplasm
• UniProt ID: TPSNR_HUMAN
• PDB ID: 5WER; 7RNO
• Pfam ID: PF07654 ; PF07686
• Sequence:
  MGTQEGWCLLLCLALSGAAETKPHPAEGQWRAVDVVLDCFLAKDGAHRGALASSEDRARA
  SLVLKQVPVLDDGSLEDFTDFQGGTLAQDDPPIIFEASVDLVQIPQAEALLHADCSGKEV
  TCEISRYFLQMTETTVKTAAWFMANMQVSGGGPSISLVMKTPRVTKNEALWHPTLNLPLS
  PQGTVRTAVEFQVMTQTQSLSFLLGSSASLDCGFSMAPGLDLISVEWRLQHKGRGQLVYS
  WTAGQGQAVRKGATLEPAQLGMARDASLTLPGLTIQDEGTYICQITTSLYRAQQIIQLNI
  QASPKVRLSLANEALLPTLICDIAGYYPLDVVVTWTREELGGSPAQVSGASFSSLRQSVA
  GTYSISSSLTAEPGSAGATYTCQVTHISLEEPLGASTQVVPPERRTALGVIFASSLFLLA
  LMFLGLQRRQAPTGLGLLQAERWETTSCADTQSSHLHEDRTARVSQPS
• Function: Component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M. Association between TAPBPR and MHC class I occurs in the absence of a functional peptide-loading complex (PLC).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

11 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 Tapasin-related protein (TAPBPL).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tapasin-related protein (TAPBPL).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tapasin-related protein (TAPBPL).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tapasin-related protein (TAPBPL).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tapasin-related protein (TAPBPL).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tapasin-related protein (TAPBPL).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tapasin-related protein (TAPBPL).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Tapasin-related protein (TAPBPL).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tapasin-related protein (TAPBPL).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tapasin-related protein (TAPBPL).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tapasin-related protein (TAPBPL).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Tapasin-related protein (TAPBPL).	[8]

References

• [1] Further examination of the candidate genes in chromosome 12p13 locus for late-onset Alzheimer disease.Neurogenetics. 2008 May;9(2):127-38. doi: 10.1007/s10048-008-0122-8. Epub 2008 Mar 14.
• [2] Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules.Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9353-E9361. doi: 10.1073/pnas.1809465115. Epub 2018 Sep 13.
• [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] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [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] 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.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [12] 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.
• [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] 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.