Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUM63MK)

• DOT Name: Lysosomal amino acid transporter 1 homolog (SLC66A1)
• Synonyms: PQ-loop repeat-containing protein 2; Solute carrier family 66 member 1
• Gene Name: SLC66A1
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cystinosis
  Gastric cancer
  Hypothyroidism
  Neoplasm
  Stomach cancer
  Lysosomal storage disease
• UniProt ID: LAAT1_HUMAN
• Pfam ID: PF04193
• Sequence:
  MVWKKLGSRNFSSCPSGSIQWIWDVLGECAQDGWDEASVGLGLISILCFAASTFPQFIKA
  YKTGNMDQALSLWFLLGWIGGDSCNLIGSFLADQLPLQTYTAVYYVLADLVMLTLYFYYK
  FRTRPSLLSAPINSVLLFLMGMACATPLLSAAGPVAAPREAFRGRALLSVESGSKPFTRQ
  EVIGFVIGSISSVLYLLSRLPQIRTNFLRKSTQGISYSLFALVMLGNTLYGLSVLLKNPE
  EGQSEGSYLLHHLPWLVGSLGVLLLDTIISIQFLVYRRSTAASELEPLLPS
• Function: Amino acid transporter that specifically mediates the pH-dependent export of the cationic amino acids arginine, histidine and lysine from lysosomes.
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Cystinosis	DISXY3VI	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[3]
Lysosomal storage disease	DIS6QM6U	Limited	Biomarker	[5]

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 Lysosomal amino acid transporter 1 homolog (SLC66A1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lysosomal amino acid transporter 1 homolog (SLC66A1).	[12]

References

• [1] Identification of TMEM208 and PQLC2 as reference genes for normalizing mRNA expression in colorectal cancer treated with aspirin.Oncotarget. 2017 Apr 4;8(14):22759-22771. doi: 10.18632/oncotarget.15191.
• [2] Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy.Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):E3434-43. doi: 10.1073/pnas.1211198109. Epub 2012 Nov 20.
• [3] Cationic amino acid transporter PQLC2 is a potential therapeutic target in gastric cancer.Cancer Sci. 2019 Apr;110(4):1453-1463. doi: 10.1111/cas.13966. Epub 2019 Mar 19.
• [4] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [5] LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis.Science. 2012 Jul 20;337(6092):351-4. doi: 10.1126/science.1220281.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] 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.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] 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.