Protein: Mucolipin-1 (ML1) (MG-2) (Mucolipidin) (Transient receptor potential channel mucolipin 1) (TRPML1) (Q9GZU1)
Organism: Homo sapiens (Human)
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).
Subcellular location: Late endosome membrane {ECO:0000269|PubMed:15178326, ECO:0000269|PubMed:21224396}; Multi-pass membrane protein {ECO:0000269|PubMed:29019983}. Lysosome membrane {ECO:0000269|PubMed:12459486, ECO:0000269|PubMed:21224396, ECO:0000269|PubMed:25733853, ECO:0000305|PubMed:16497227, ECO:0000305|PubMed:16978393}; Multi-pass membrane protein {ECO:0000269|PubMed:29019983}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:12459486}; Multi-pass membrane protein {ECO:0000269|PubMed:29019983}. Cell projection, phagocytic cup {ECO:0000250|UniProtKB:Q99J21}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q99J21}; Multi-pass membrane protein {ECO:0000269|PubMed:29019983}. Cell membrane {ECO:0000305|PubMed:29019983}; Multi-pass membrane protein {ECO:0000269|PubMed:29019983}. Note=Delivery from the trans-Golgi to lysosomes seems to occur mainly in a direct intracellular manner without intermediate delivery to the plasma membrane (PubMed:16497227). Under normal conditions, restricted to intracellular compartments so that only a very minor proportion is present at the cell membrane (PubMed:12459486, PubMed:18794901, PubMed:28112729, PubMed:29019983). {ECO:0000269|PubMed:12459486, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:28112729, ECO:0000269|PubMed:29019983, ECO:0000305|PubMed:16497227}.
Interaction partners:
- Mucolipin-2
- Mucolipin-3
- Transcription factor EB
- FERM domain-containing protein 6
- Patatin-like phospholipase domain-containing protein 6
- Polycystin-2
- Programmed cell death protein 6
- Sialidase-3
- Two pore channel protein 2
- Transient receptor potential cation channel subfamily M member 4
Sequence:
MTAPAGPRGSETERLLTPNPGYGTQAGPSPAPPTPPEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLMLQVVKILVVTVQLILFGLSNQLAVTFREENTIAFRHLFLLGYSDGADDTFAAYTREQLYQAIFHAVDQYLALPDVSLGRYAYVRGGGDPWTNGSGLALCQRYYHRGHVDPANDTFDIDPMVVTDCIQVDPPERPPPPPSDDLTLLESSSSYKNLTLKFHKLVNVTIHFRLKTINLQSLINNEIPDCYTFSVLITFDNKAHSGRIPISLETQAHIQECKHPSVFQHGDNSFRLLFDVVVILTCSLSFLLCARSLLRGFLLQNEFVGFMWRQRGRVISLWERLEFVNGWYILLVTSDVLTISGTIMKIGIEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFFHNYNILIATLRVALPSVMRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVTFAAMQAQQGRSSLVWLFSQLYLYSFISLFIYMVLSLFIALITGAYDTIKHPGGAGAEESELQAYIAQCQDSPTSGKFRRGSGSACSLLCCCGRDPSEEHSLLVN