Details of Drug Off-Target (DOT)

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

• DOT Name: Leucine zipper putative tumor suppressor 3 (LZTS3)
• Synonyms: ProSAP-interacting protein 1; ProSAPiP1
• Gene Name: LZTS3
• Related Disease:
  Advanced cancer
  Neoplasm
  Non-small-cell lung cancer
  Amyotrophic lateral sclerosis
  Huntington disease
• UniProt ID: LZTS3_HUMAN
• Pfam ID: PF06818
• Sequence:
  MAKLETLPVRADPGRDPLLAFAPRPSELGPPDPRLAMGSVGSGVAHAQEFAMKSVGTRTG
  GGGSQGSFPGPRGSGSGASRERPGRYPSEDKGLANSLYLNGELRGSDHTDVCGNVVGSSG
  GSSSSGGSDKAPPQYREPSHPPKLLATSGKLDQCSEPLVRPSAFKPVVPKNFHSMQNLCP
  PQTNGTPEGRQGPGGLKGGLDKSRTMTPAGGSGSGLSDSGRNSLTSLPTYSSSYSQHLAP
  LSASTSHINRIGTASYGSGSGGSSGGGSGYQDLGTSDSGRASSKSGSSSSMGRPGHLGSG
  EGGGGGLPFAACSPPSPSALIQELEERLWEKEQEVAALRRSLEQSEAAVAQVLEERQKAW
  ERELAELRQGCSGKLQQVARRAQRAQQGLQLQVLRLQQDKKQLQEEAARLMRQREELEDK
  VAACQKEQADFLPRIEETKWEVCQKAGEISLLKQQLKDSQADVSQKLSEIVGLRSQLREG
  RASLREKEEQLLSLRDSFSSKQASLELGEGELPAACLKPALTPVDPAEPQDALATCESDE
  AKMRRQAGVAAAASLVSVDGEAEAGGESGTRALRREVGRLQAELAAERRARERQGASFAE
  ERRVWLEEKEKVIEYQKQLQLSYVEMYQRNQQLERRLRERGAAGGASTPTPQHGEEKKAW
  TPSRLERIESTEI
• Function: May be involved in promoting the maturation of dendritic spines, probably via regulating SIPA1L1 levels at the postsynaptic density of synapses.
• KEGG Pathway: Glutamatergic sy.pse (hsa04724)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[3]
Huntington disease	DISQPLA4	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Leucine zipper putative tumor suppressor 3 (LZTS3).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leucine zipper putative tumor suppressor 3 (LZTS3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Leucine zipper putative tumor suppressor 3 (LZTS3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine zipper putative tumor suppressor 3 (LZTS3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leucine zipper putative tumor suppressor 3 (LZTS3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Leucine zipper putative tumor suppressor 3 (LZTS3).	[10]

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 decreases the methylation of Leucine zipper putative tumor suppressor 3 (LZTS3).	[7]

References

• [1] In silico characterization of LZTS3, a potential tumor suppressor.Oncol Rep. 2005 Aug;14(2):547-51.
• [2] MiR-1275 promotes non-small cell lung cancer cell proliferation and metastasis by regulating LZTS3 expression.Eur Rev Med Pharmacol Sci. 2018 May;22(9):2680-2687. doi: 10.26355/eurrev_201805_14964.
• [3] Rare homozygosity in amyotrophic lateral sclerosis suggests the contribution of recessive variants to disease genetics.J Neurol Sci. 2019 Jul 15;402:62-68. doi: 10.1016/j.jns.2019.05.006. Epub 2019 May 8.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] BET bromodomain protein inhibition is a therapeutic option for medulloblastoma. Oncotarget. 2013 Nov;4(11):2080-95.
• [9] 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.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.