Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7KWGMR)

• DOT Name: LanC-like protein 2 (LANCL2)
• Synonyms: Testis-specific adriamycin sensitivity protein
• Gene Name: LANCL2
• UniProt ID: LANC2_HUMAN
• PDB ID: 6WQ1
• Pfam ID: PF05147
• Sequence:
  MGETMSKRLKLHLGGEAEMEERAFVNPFPDYEAAAGALLASGAAEETGCVRPPATTDEPG
  LPFHQDGKIIHNFIRRIQTKIKDLLQQMEEGLKTADPHDCSAYTGWTGIALLYLQLYRVT
  CDQTYLLRSLDYVKRTLRNLNGRRVTFLCGDAGPLAVGAVIYHKLRSDCESQECVTKLLQ
  LQRSVVCQESDLPDELLYGRAGYLYALLYLNTEIGPGTVCESAIKEVVNAIIESGKTLSR
  EERKTERCPLLYQWHRKQYVGAAHGMAGIYYMLMQPAAKVDQETLTEMVKPSIDYVRHKK
  FRSGNYPSSLSNETDRLVHWCHGAPGVIHMLMQAYKVFKEEKYLKEAMECSDVIWQRGLL
  RKGYGICHGTAGNGYSFLSLYRLTQDKKYLYRACKFAEWCLDYGAHGCRIPDRPYSLFEG
  MAGAIHFLSDVLGPETSRFPAFELDSSKRD
• Function: Necessary for abscisic acid (ABA) binding on the cell membrane and activation of the ABA signaling pathway in granulocytes.
• Tissue Specificity: Expressed in brain and testis.

Molecular Interaction Atlas (MIA) of This DOT

10 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 LanC-like protein 2 (LANCL2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of LanC-like protein 2 (LANCL2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LanC-like protein 2 (LANCL2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of LanC-like protein 2 (LANCL2).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of LanC-like protein 2 (LANCL2).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of LanC-like protein 2 (LANCL2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of LanC-like protein 2 (LANCL2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of LanC-like protein 2 (LANCL2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of LanC-like protein 2 (LANCL2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of LanC-like protein 2 (LANCL2).	[11]

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 LanC-like protein 2 (LANCL2).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [9] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.