Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUVG424)

• DOT Name: Leukocyte-specific transcript 1 protein (LST1)
• Synonyms: Protein B144
• Gene Name: LST1
• Related Disease:
  Arthritis
  Advanced cancer
  Autoimmune disease
  Dermatitis
  Inflammatory bowel disease
  Neoplasm
  Nephritis
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Type-1 diabetes
  Graves disease
  Neural tube defect
• UniProt ID: LST1_HUMAN
• Pfam ID: PF05083
• Sequence:
  MLSRNDDICIYGGLGLGGLLLLAVVLLSACLCWLHRRVKRLERSWAQGSSEQELHYASLQ
  RLPVPSSEGPDLRGRDKRGTKEDPRADYACIAENKPT
• Function: Possible role in modulating immune responses. Induces morphological changes including production of filopodia and microspikes when overexpressed in a variety of cell types and may be involved in dendritic cell maturation. Isoform 1 and isoform 2 have an inhibitory effect on lymphocyte proliferation.
• Tissue Specificity: Expressed in lung, tonsil, thymus, placenta, kidney, fetal spleen, fetal liver and brain.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[2]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[3]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Nephritis	DISQZQ70	Strong	Genetic Variation	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[6]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Graves disease	DISU4KOQ	moderate	Genetic Variation	[9]
Neural tube defect	DIS5J95E	Disputed	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[14]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Leukocyte-specific transcript 1 protein (LST1).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[11]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leukocyte-specific transcript 1 protein (LST1).	[18]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Leukocyte-specific transcript 1 protein (LST1).	[21]

3 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 Leukocyte-specific transcript 1 protein (LST1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leukocyte-specific transcript 1 protein (LST1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Leukocyte-specific transcript 1 protein (LST1).	[20]

References

• [1] Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis.Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):E3716-24. doi: 10.1073/pnas.1600567113. Epub 2016 Jun 14.
• [2] LST1: A multifunctional gene encoded in the MHC class III region.Immunobiology. 2018 Nov;223(11):699-708. doi: 10.1016/j.imbio.2018.07.018. Epub 2018 Jul 17.
• [3] Identification of functional haplotypes in the promoter region of the LST1 gene.Biochem Genet. 2014 Aug;52(7-8):365-71. doi: 10.1007/s10528-014-9653-x. Epub 2014 May 7.
• [4] Regulated expression of leukocyte-specific transcript (LST) 1 in human intestinal inflammation.Inflamm Res. 2014 Jul;63(7):513-7. doi: 10.1007/s00011-014-0732-6. Epub 2014 Mar 30.
• [5] SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans.PLoS Genet. 2017 Dec 12;13(12):e1007121. doi: 10.1371/journal.pgen.1007121. eCollection 2017 Dec.
• [6] Haplotype-specific gene expression profiles in a telomeric major histocompatibility complex gene cluster and susceptibility to autoimmune diseases.Genes Immun. 2006 Dec;7(8):625-31. doi: 10.1038/sj.gene.6364339. Epub 2006 Sep 14.
• [7] Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids.Clin Exp Rheumatol. 2016 Jul-Aug;34(4):685-9. Epub 2016 Jun 22.
• [8] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [9] PVU II polymorphism of LST-1 (leucocyte specific transcript-1) in type I diabetes mellitus, Graves' disease and healthy controls.Eur J Immunogenet. 1995 Jun;22(3):277-82. doi: 10.1111/j.1744-313x.1995.tb00242.x.
• [10] Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders.Clin Chem. 2006 Nov;52(11):2013-20. doi: 10.1373/clinchem.2006.074971. Epub 2006 Sep 28.
• [11] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [14] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [15] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [16] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [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] 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.
• [19] Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.