Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU3V04B)

• DOT Name: Mucolipin-2 (MCOLN2)
• Synonyms: Transient receptor potential channel mucolipin 2; TRPML2
• Gene Name: MCOLN2
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
  Neoplasm
• UniProt ID: MCLN2_HUMAN
• PDB ID: 6HRR; 6HRS
• Pfam ID: PF21381 ; PF08016
• Sequence:
  MARQPYRFPQARIPERGSGVFRLTVRNAMAHRDSEMKEECLREDLKFYFMSPCEKYRARR
  QIPWKLGLQILKIVMVTTQLVRFGLSNQLVVAFKEDNTVAFKHLFLKGYSGTDEDDYSCS
  VYTQEDAYESIFFAINQYHQLKDITLGTLGYGENEDNRIGLKVCKQHYKKGTMFPSNETL
  NIDNDVELDCVQLDLQDLSKKPPDWKNSSFFRLEFYRLLQVEISFHLKGIDLQTIHSREL
  PDCYVFQNTIIFDNKAHSGKIKIYFDSDAKIEECKDLNIFGSTQKNAQYVLVFDAFVIVI
  CLASLILCTRSIVLALRLRKRFLNFFLEKYKRPVCDTDQWEFINGWYVLVIISDLMTIIG
  SILKMEIKAKNLTNYDLCSIFLGTSTLLVWVGVIRYLGYFQAYNVLILTMQASLPKVLRF
  CACAGMIYLGYTFCGWIVLGPYHDKFENLNTVAECLFSLVNGDDMFATFAQIQQKSILVW
  LFSRLYLYSFISLFIYMILSLFIALITDSYDTIKKFQQNGFPETDLQEFLKECSSKEEYQ
  KESSAFLSCICCRRRKRSDDHLIPIS
• Function: Nonselective cation channel probably playing a role in the regulation of membrane trafficking events. Acts as a Ca(2+)-permeable cation channel with inwardly rectifying activity. May activate ARF6 and be involved in the trafficking of GPI-anchored cargo proteins to the cell surface via the ARF6-regulated recycling pathway. May play a role in immune processes. In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells. In the innate immune response, may play a role in the regulation of chemokine secretion and macrophage migration. Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events.
• KEGG Pathway: Calcium sig.ling pathway (hsa04020)
• Reactome Pathway: TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

7 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 Mucolipin-2 (MCOLN2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mucolipin-2 (MCOLN2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mucolipin-2 (MCOLN2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mucolipin-2 (MCOLN2).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Mucolipin-2 (MCOLN2).	[6]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Mucolipin-2 (MCOLN2).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Mucolipin-2 (MCOLN2).	[9]

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 increases the methylation of Mucolipin-2 (MCOLN2).	[8]

References

• [1] Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression.Oncotarget. 2016 Jul 12;7(28):43654-43668. doi: 10.18632/oncotarget.9661.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [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] 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.