Protein: Mucolipin-1 (Mucolipidin) (Transient receptor potential-mucolipin 1) (TRPML1) (Q99J21)
Organism: Mus musculus (Mouse)
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. 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 (By similarity). 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 (By similarity). In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells.
Subcellular location: Late endosome membrane {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein {ECO:0000269|PubMed:29019981}. Lysosome membrane {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein {ECO:0000269|PubMed:29019981}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein {ECO:0000269|PubMed:29019981}. Cell projection, phagocytic cup {ECO:0000269|PubMed:23993788}. Cytoplasmic vesicle, phagosome membrane {ECO:0000269|PubMed:23993788}; Multi-pass membrane protein {ECO:0000269|PubMed:29019981}. Cell membrane {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein {ECO:0000269|PubMed:29019981}. Note=Delivery from the trans-Golgi to lysosomes seems to occur mainly in a direct intracellular manner without intermediate delivery to the plasma membrane (By similarity). Under normal conditions, restricted to intracellular compartments so that only a very minor proportion is present at the cell membrane (PubMed:29019981). {ECO:0000250|UniProtKB:Q9GZU1, ECO:0000269|PubMed:29019981}.
Interaction partners:
- Mucolipin-2
- Mucolipin-3
- Transcription factor EB
- Transient receptor potential cation channel subfamily M member 4
- Short transient receptor potential channel 3
- Two pore channel protein 2
- Transient receptor potential cation channel subfamily V member 1
- Transient receptor potential cation channel subfamily V member 2
- Transient receptor potential cation channel subfamily A member 1
- Lysosome-associated membrane glycoprotein 1
Sequence:
MATPAGRRASETERLLTPNPGYGTQVGTSPAPTTPTEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLMLQVVKILVVTVQLILFGLSNQLVVTFREENTIAFRHLFLLGYSDGSDDTFAAYTQEQLYQAIFYAVDQYLILPEISLGRYAYVRGGGGPWANGSALALCQRYYHRGHVDPANDTFDIDPRVVTDCIQVDPPDRPPDIPSEDLDFLDGSASYKNLTLKFHKLINVTIHFQLKTINLQSLINNEIPDCYTFSILITFDNKAHSGRIPIRLETKTHIQECKHPSVSRHGDNSFRLLFDVVVILTCSLSFLLCARSLLRGFLLQNEFVVFMWRRRGREISLWERLEFVNGWYILLVTSDVLTISGTVMKIGIEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFFHKYNILIATLRVALPSVMRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVTFAAMQAQQGHSSLVWLFSQLYLYSFISLFIYMVLSLFIALITGAYDTIKHPGGTGTEKSELQAYIEQCQDSPTSGKFRRGSGSACSLFCCCGRDSPEDHSLLVN