Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

MCOLN1 (Q9GZU1) - Overview - Molecular Target Synopsis

Protein


MCOLN1, Mucolipin-1
UniProt Q9GZU1

Also Known as MCLN1_HUMAN, MCOLN1, ML4

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. Homotetramer (PubMed:28112729, PubMed:29019983). Homooligomer (PubMed:14749347). Can heterooligomerize with MCOLN2 or MCOLN3; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific (PubMed:19885840). Interacts with PDCD6 (PubMed:19864416). Interacts with TMEM163 (PubMed:25130899). Interacts with LAPTM4B (PubMed:21224396).

6E7Z
CRYO-EM STRUCTURE OF HUMAN TRPML1 WITH ML-SA1 AND PI35P2
RCSB/PDB
Inspect Structure
See all 3D Structures for MCOLN1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MCOLN1 is active in the following subcellular-locations: cell membrane, cell projection, cytoplasmic vesicle, cytoplasmic vesicle membrane, late endosome membrane, lysosome membrane, phagocytic cup, phagosome membrane.
GO terms: MCOLN1 is active in the following subcellular-locations: cell projection, cytosol, endosome membrane, integral component of membrane, integral component of plasma membrane, late endosome, late endosome membrane, lysosomal membrane, lysosome, phagocytic cup, phagocytic vesicle membrane, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MCOLN1 has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_5, UACC_257, OVCAR_4

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H446, SNU-398, MDA-MB-134-VI

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HUVEC, HeLa-S3

(see details)

3D Structures


For MCOLN1 there are:
8 structures (23 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MCOLN1 has been screened with compounds ( bioactivities). (see details)