MCOLN3

Domain

The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.

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 (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840, PubMed:29106414). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Also permeable to Mg(2+), Na(+) and K(+) (By similarity). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).

Post-translational modifications

N-glycosylated.

Sequence Similarities

Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN3 sub-subfamily.

Cellular localization

• Cell membrane
• Multi-pass membrane protein
• Early endosome membrane
• Multi-pass membrane protein
• Late endosome membrane
• Multi-pass membrane protein
• Lysosome membrane
• Multi-pass membrane protein
• Cytoplasmic vesicle
• Autophagosome membrane
• Recycles between the plasma membrane and intracellular compartments by a dynamin-dependent endocytic pathway (PubMed:19522758). Under normal conditions, only a very minor proportion is present at the cell membrane (PubMed:19522758). In the cochlea located at the base of stereocilia near the position of the ankle links (By similarity).

Alternative names

Mucolipin-3, Transient receptor potential channel mucolipin 3, TRPML3, MCOLN3

Database links

swissprot:Q8TDD5 entrezGene:55283 omim:607400 swissprot:Q5T4H5