Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2XI2JG)

• DOT Name: Lysosomal-associated transmembrane protein 5 (LAPTM5)
• Synonyms: Lysosomal-associated multitransmembrane protein 5; Retinoic acid-inducible E3 protein
• Gene Name: LAPTM5
• Related Disease:
  Advanced cancer
  Bladder cancer
  Glioblastoma multiforme
  IgA nephropathy
  Lymphoma
  Plasma cell myeloma
  Sjogren syndrome
  Urinary bladder cancer
  Urinary bladder neoplasm
  Lupus nephritis
  Systemic lupus erythematosus
  Neoplasm
  Waldenstrom macroglobulinemia
• UniProt ID: LAPM5_HUMAN
• Pfam ID: PF03821
• Sequence:
  MDPRLSTVRQTCCCFNVRIATTALAIYHVIMSVLLFIEHSVEVAHGKASCKLSQMGYLRI
  ADLISSFLLITMLFIISLSLLIGVVKNREKYLLPFLSLQIMDYLLCLLTLLGSYIELPAY
  LKLASRSRASSSKFPLMTLQLLDFCLSILTLCSSYMEVPTYLNFKSMNHMNYLPSQEDMP
  HNQFIKMMIIFSIAFITVLIFKVYMFKCVWRCYRLIKCMNSVEEKRNSKMLQKVVLPSYE
  EALSLPSKTPEGGPAPPPYSEV
• Function: May have a special functional role during embryogenesis and in adult hematopoietic cells.
• Tissue Specificity: Preferentially expressed in adult hematopoietic tissues. High levels in lymphoid and myeloid tissues. Highly expressed in peripheral blood leukocytes, thymus, spleen and lung, followed by placenta, liver and kidney.
• KEGG Pathway: Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[4]
Lymphoma	DISN6V4S	Strong	Biomarker	[1]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[5]
Sjogren syndrome	DISUBX7H	Strong	Altered Expression	[6]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[2]
Lupus nephritis	DISCVGPZ	moderate	Altered Expression	[7]
Systemic lupus erythematosus	DISI1SZ7	moderate	Altered Expression	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
Waldenstrom macroglobulinemia	DIS9O23I	Limited	Biomarker	[8]

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 Lysosomal-associated transmembrane protein 5 (LAPTM5).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[15]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[16]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Lysosomal-associated transmembrane protein 5 (LAPTM5).	[21]

References

• [1] Stage-specific expression of Clast6/E3/LAPTM5 during B cell differentiation: elevated expression in human B lymphomas.Int J Oncol. 2003 Feb;22(2):301-4.
• [2] Downregulation of LAPTM5 suppresses cell proliferation and viability inducing cell cycle arrest at G0/G1 phase of bladder cancer cells.Int J Oncol. 2017 Jan;50(1):263-271. doi: 10.3892/ijo.2016.3788. Epub 2016 Dec 5.
• [3] Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration.Mol Oncol. 2020 Jan;14(1):159-179. doi: 10.1002/1878-0261.12595. Epub 2019 Dec 11.
• [4] The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.PLoS One. 2014 Aug 18;9(8):e103413. doi: 10.1371/journal.pone.0103413. eCollection 2014.
• [5] Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma.Leukemia. 2003 Aug;17(8):1650-7. doi: 10.1038/sj.leu.2403026.
• [6] Transcriptional and metabolic pre-B cell receptor-mediated checkpoints: implications for autoimmune diseases.Mol Immunol. 2014 Dec;62(2):315-20. doi: 10.1016/j.molimm.2014.01.009. Epub 2014 Mar 4.
• [7] Expression and Polymorphisms of Lysosome-Associated Protein Transmembrane 5 (LAPTM5) in Patients with Systemic Lupus Erythematosus in a Chinese Population.Biochem Genet. 2015 Aug;53(7-8):200-10. doi: 10.1007/s10528-015-9682-0. Epub 2015 May 22.
• [8] Exome sequencing reveals recurrent germ line variants in patients with familial Waldenstrm macroglobulinemia.Blood. 2016 May 26;127(21):2598-606. doi: 10.1182/blood-2015-11-680199. Epub 2016 Feb 22.
• [9] 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.
• [10] 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.
• [11] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [12] 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.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] 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.
• [15] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [16] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [17] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [18] 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.
• [19] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [20] Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
• [21] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.