Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7IIPM)

• DOT Name: LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2)
• Synonyms: LIM-like protein 2; Particularly interesting new Cys-His protein 2; PINCH-2
• Gene Name: LIMS2
• Related Disease:
  Advanced cancer
  Carcinoma
  Colon cancer
  Colon carcinoma
  Gastric cancer
  Gastric neoplasm
  Malignant mesothelioma
  Mesothelioma
  Serous cystadenocarcinoma
  Stomach cancer
  Muscular dystrophy
  Autosomal recessive limb-girdle muscular dystrophy type 2W
  Cardiomyopathy
  Limb-girdle muscular dystrophy
• UniProt ID: LIMS2_HUMAN
• PDB ID: 3IXE
• Pfam ID: PF00412
• Sequence:
  MTGSNMSDALANAVCQRCQARFSPAERIVNSNGELYHEHCFVCAQCFRPFPEGLFYEFEG
  RKYCEHDFQMLFAPCCGSCGEFIIGRVIKAMNNNWHPGCFRCELCDVELADLGFVKNAGR
  HLCRPCHNREKAKGLGKYICQRCHLVIDEQPLMFRSDAYHPDHFNCTHCGKELTAEAREL
  KGELYCLPCHDKMGVPICGACRRPIEGRVVNALGKQWHVEHFVCAKCEKPFLGHRHYEKK
  GLAYCETHYNQLFGDVCYNCSHVIEGDVVSALNKAWCVSCFSCSTCNSKLTLKNKFVEFD
  MKPVCKRCYEKFPLELKKRLKKLSELTSRKAQPKATDLNSA
• Function: Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Plays a role in modulating cell spreading and migration.
• Reactome Pathway: Cell-extracellular matrix interactions (R-HSA-446353)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[3]
Gastric neoplasm	DISOKN4Y	Strong	Posttranslational Modification	[3]
Malignant mesothelioma	DISTHJGH	Strong	Altered Expression	[1]
Mesothelioma	DISKWK9M	Strong	Altered Expression	[1]
Serous cystadenocarcinoma	DISVK716	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[3]
Muscular dystrophy	DISJD6P7	moderate	Genetic Variation	[4]
Autosomal recessive limb-girdle muscular dystrophy type 2W	DISFNUC7	Supportive	Autosomal recessive	[4]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[4]
Limb-girdle muscular dystrophy	DISI9Y1Z	Limited	Biomarker	[4]

7 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 LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of LIM and senescent cell antigen-like-containing domain protein 2 (LIMS2).	[11]

References

• [1] PINCH-2 expression in cancers involving serosal effusions using quantitative PCR.Cytopathology. 2011 Feb;22(1):22-9. doi: 10.1111/j.1365-2303.2010.00757.x.
• [2] PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity.Int J Cancer. 2015 May 15;136(10):2273-83. doi: 10.1002/ijc.29273. Epub 2014 Oct 30.
• [3] The epigenetic silencing of LIMS2 in gastric cancer and its inhibitory effect on cell migration.Biochem Biophys Res Commun. 2006 Oct 27;349(3):1032-40. doi: 10.1016/j.bbrc.2006.08.128. Epub 2006 Aug 30.
• [4] LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues. Clin Genet. 2015 Dec;88(6):558-64. doi: 10.1111/cge.12561. Epub 2015 Feb 26.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] 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.
• [12] 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.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.