Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC672RM)

• DOT Name: Lysosome-associated membrane glycoprotein 5 (LAMP5)
• Synonyms: Brain and dendritic cell-associated LAMP; Brain-associated LAMP-like protein; BAD-LAMP; Lysosome-associated membrane protein 5; LAMP-5
• Gene Name: LAMP5
• Related Disease:
  Acute myelogenous leukaemia
  Blastic plasmacytoid dendritic cell neoplasm
  Breast neoplasm
  Advanced cancer
  leukaemia
  Leukemia
• UniProt ID: LAMP5_HUMAN
• Pfam ID: PF01299
• Sequence:
  MDLQGRGVPSIDRLRVLLMLFHTMAQIMAEQEVENLSGLSTNPEKDIFVVRENGTTCLMA
  EFAAKFIVPYDVWASNYVDLITEQADIALTRGAEVKGRCGHSQSELQVFWVDRAYALKML
  FVKESHNMSKGPEATWRLSKVQFVYDSSEKTHFKDAVSAGKHTANSHHLSALVTPAGKSY
  ECQAQQTISLASSDPQKTVTMILSAVHIQPFDIISDFVFSEEHKCPVDEREQLEETLPLI
  LGLILGLVIMVTLAIYHVHHKMTANQVQIPRDRSQYKHMG
• Function: Plays a role in short-term synaptic plasticity in a subset of GABAergic neurons in the brain.
• Tissue Specificity: Expressed in plasmocytoid dendritic cells. Expressed in suprabasal skin keratinocytes and squamous cells (at protein level). Expressed in the brain and weakly in spleen and skin. Expressed in plasmocytoid dendritic cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Blastic plasmacytoid dendritic cell neoplasm	DISLEJU7	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
leukaemia	DISS7D1V	Limited	Biomarker	[4]
Leukemia	DISNAKFL	Limited	Biomarker	[4]

5 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 Lysosome-associated membrane glycoprotein 5 (LAMP5).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysosome-associated membrane glycoprotein 5 (LAMP5).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lysosome-associated membrane glycoprotein 5 (LAMP5).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Lysosome-associated membrane glycoprotein 5 (LAMP5).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Lysosome-associated membrane glycoprotein 5 (LAMP5).	[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 affects the methylation of Lysosome-associated membrane glycoprotein 5 (LAMP5).	[8]

References

• [1] Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN).Blood Cancer J. 2019 Dec 6;9(12):99. doi: 10.1038/s41408-019-0262-0.
• [2] BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells.Nat Commun. 2017 Oct 13;8(1):913. doi: 10.1038/s41467-017-00695-1.
• [3] LAMPs: Shedding light on cancer biology.Semin Oncol. 2017 Aug;44(4):239-253. doi: 10.1053/j.seminoncol.2017.10.013. Epub 2017 Nov 4.
• [4] Activation of the Lysosome-Associated Membrane Protein LAMP5 by DOT1L Serves as a Bodyguard for MLL Fusion Oncoproteins to Evade Degradation in Leukemia.Clin Cancer Res. 2019 May 1;25(9):2795-2808. doi: 10.1158/1078-0432.CCR-18-1474. Epub 2019 Jan 16.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] 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.