Tchem MCOLN1 Mucolipin-1

Protein Summary

Description

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 (PubMed:11013137, PubMed:12459486, PubMed:15336987, PubMed:14749347, PubMed:29019983). 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 (PubMed:16978393). 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 (PubMed:27787197, PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (PubMed:27357649). Functions as a Fe(2+) permeable channel in late endosomes and lysosomes (PubMed:18794901). Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (PubMed:25130899) In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity). May contribute to cellular lipase activity within the late endosomal pathway or at the cell surface which may be involved in processes of membrane reshaping and vesiculation, especially the growth of tubular structures. However, it is not known, whether it conveys the enzymatic activity directly, or merely facilitates the activity of an associated phospholipase. This gene encodes a memberof the transient receptor potential (TRP) cation channel gene family. The transmembrane protein localizes to intracellular vesicular membranes including lysosomes, and functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. The channel is permeable to Ca(2+), Fe(2+), Na(+), K(+), and H(+), and is modulated by changes in Ca(2+) concentration. Mutations in this gene result in mucolipidosis type IV. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• Q9GZU1
• D6W647
• Q7Z4F7
• Q9H292
• Q9H4B3
• Q9H4B5
• ML1

Gene Name

• MCOLN1

Ensembl ID

• ENST00000264079
• ENSP00000264079
• ENSG00000090674

Symbol

• ML4
• ML1
• ML4
• MG-2
• MLIV
• MST080
• TRPML1
• MSTP080
• TRP-ML1
• TRPM-L1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.84
molecular function	0.81
cellular component	0.8
transcription factor binding site profile	0.78
tissue sample	0.67

Protein Classes

PANTHER Classes

Protein / Transporter / Ion Channel / Mucolipin-1

DTO Classes

Protein / Ion Channel / Transient Receptor Potential Calcium Channel (Trp-cc) Family / Polycystin Subfamily / Mcoln1 Sub-subfamily / Mucolipin-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 326.77   (req: < 5)

Gene RIFs: 77   (req: <= 3)

Antibodies: 152   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 326.77   (req: >= 5)

Gene RIFs: 77   (req: > 3)

Antibodies: 152   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 16

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0