Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT9XBVO)

• DTT Name: Mucolipin-1 (TRPML1)
• Synonyms: Transient receptor potential channel mucolipin 1; TRPML1; Mucolipidin; MSTP080; ML4; ML1; MG-2
• Gene Name: MCOLN1
• DTT Type: Preclinical target; [1]
• UniProt ID: MCLN1_HUMAN
• TTD ID: T28309
• Sequence:
  MTAPAGPRGSETERLLTPNPGYGTQAGPSPAPPTPPEEEDLRRRLKYFFMSPCDKFRAKG
  RKPCKLMLQVVKILVVTVQLILFGLSNQLAVTFREENTIAFRHLFLLGYSDGADDTFAAY
  TREQLYQAIFHAVDQYLALPDVSLGRYAYVRGGGDPWTNGSGLALCQRYYHRGHVDPAND
  TFDIDPMVVTDCIQVDPPERPPPPPSDDLTLLESSSSYKNLTLKFHKLVNVTIHFRLKTI
  NLQSLINNEIPDCYTFSVLITFDNKAHSGRIPISLETQAHIQECKHPSVFQHGDNSFRLL
  FDVVVILTCSLSFLLCARSLLRGFLLQNEFVGFMWRQRGRVISLWERLEFVNGWYILLVT
  SDVLTISGTIMKIGIEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFFHNYNILIATLRV
  ALPSVMRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVTFAAM
  QAQQGRSSLVWLFSQLYLYSFISLFIYMVLSLFIALITGAYDTIKHPGGAGAEESELQAY
  IAQCQDSPTSGKFRRGSGSACSLLCCCGRDPSEEHSLLVN
• Function: Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis. Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy. Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (By similarity). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events. By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels. Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy. Functions as a Fe(2+) permeable channel in late endosomes and lysosomes. Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity).
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Lysosome (hsa04142)
• Reactome Pathway:
  Transferrin endocytosis and recycling (R-HSA-917977)
  TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MK6-83	DMI3E0Y	Discovery agent	N.A.	Preclinical	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
phosphatidyl (3,5) inositol biphosphate	DMMHQYB	Discovery agent	N.A.	Investigative	[1]

References

• [1] PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome. Nat Commun. 2010 Jul 13;1:38.
• [2] ML-SA1, a selective TRPML agonist, inhibits DENV2 and ZIKV by promoting lysosomal acidification and protease activity. Antiviral Res. 2020 Oct;182:104922.