Mcoln1
entrez
94178
canonical
uniprot
Q99J21
canonical
ensembl
ENSMUSG00000004567
resolver
ensp
ENSMUSP00000004683
resolver
genesymbol
Mcoln1
resolver
genesymbol_syn
Trpml1
resolver
uniprot_entry
MCLN1_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments (By similarity). Lower pH by itself has an inhibitory effect on channel conductance. Channel function is transiently modulated by changes in Ca(2+) in a pH-dependent manner; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca(2+) and H(+) is suggested (PubMed:29019981). Fe(2+) channel activity is potentiated by low pH (PubMed:18794901). Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) (PubMed:29019981). {ECO:0000250|UniProtKB:Q9GZU1, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:29019981}.
uniprot
proteins
amino_acid_sequence
MATPAGRRASETERLLTPNPGYGTQVGTSPAPTTPTEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLMLQVVKILVVTVQLILFGLSNQLVVTFREENTIAFRHLFLLGYSDGSDDTFAAYTQEQLYQAIFYAVDQYLILPEISLGRYAYVRGGGGPWANGSALALCQRYYHRGHVDPANDTFDIDPRVVTDCIQVDPPDRPPDIPSEDLDFLDGSASYKNLTLKFHKLINVTIHFQLKTINLQSLINNEIPDCYTFSILITFDNKAHSGRIPIRLETKTHIQECKHPSVSRHGDNSFRLLFDVVVILTCSLSFLLCARSLLRGFLLQNEFVVFMWRRRGREISLWERLEFVNGWYILLVTSDVLTISGTVMKIGIEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFFHKYNILIATLRVALPSVMRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVTFAAMQAQQGHSSLVWLFSQLYLYSFISLFIYMVLSLFIALITGAYDTIKHPGGTGTEKSELQAYIEQCQDSPTSGKFRRGSGSACSLFCCCGRDSPEDHSLLVN
uniprot
proteins
function
FUNCTION: Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis (PubMed:17989217, PubMed:18794901, PubMed:29019981). Acts as a Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:17989217). 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 (PubMed:23993788, PubMed:27623384). 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 (PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (By similarity). Also functions as a Fe(2+) permeable channel in late endosomes and lysosomes (PubMed:18794901). Also permeable to Mg(2+), Na(+), K(+) and Cs(+) (PubMed:17989217). 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 (PubMed:17050035). {ECO:0000250|UniProtKB:Q9GZU1, ECO:0000269|PubMed:17050035, ECO:0000269|PubMed:17989217, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:23993788, ECO:0000269|PubMed:25733853, ECO:0000269|PubMed:27623384, ECO:0000269|PubMed:29019981}.; FUNCTION: 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. {ECO:0000250|UniProtKB:Q9GZU1}.
uniprot
proteins
mass_dalton
65506
uniprot
proteins
mutagenesis
MUTAGEN 232; /note="T->P: Loss of Fe(2+) transport; when associated with P-432."; /evidence="ECO:0000269|PubMed:18794901"; MUTAGEN 362; /note="D->Y: Loss of Fe(2+) transport; when associated with P-432."; /evidence="ECO:0000269|PubMed:18794901"; MUTAGEN 403; /note="R->C: Loss of Fe(2+) transport; when associated with P-432."; /evidence="ECO:0000269|PubMed:18794901"; MUTAGEN 408; /note="Missing: Decreased Fe(2+) transport; when associated with P-432."; /evidence="ECO:0000269|PubMed:18794901"; MUTAGEN 432; /note="V->P: Constitutively active channel that is targeted to the plasma membrane, and mediates strong inwardly rectifying current."; /evidence="ECO:0000269|PubMed:17989217, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:29019981"; MUTAGEN 446; /note="V->L: Loss of Fe(2+) transport; when associated with P-432."; /evidence="ECO:0000269|PubMed:18794901"; MUTAGEN 465; /note="F->L: Loss of Fe(2+) transport; when associated with P-432."; /evidence="ECO:0000269|PubMed:18794901
uniprot
proteins
post_translational_modification
PTM: Palmitoylated; involved in association with membranes. {ECO:0000250|UniProtKB:Q9GZU1}.; PTM: Phosphorylation by PKA inhibits channel activity. Dephosphorylation increases activity. {ECO:0000250|UniProtKB:Q9GZU1}.; PTM: Proteolytically cleaved probably involving multiple lysosomal proteases including cathepsin B; inhibits lysosomal channel activity. {ECO:0000250|UniProtKB:Q9GZU1}.
uniprot
proteins
protein_family
MCOLN1 sub-subfamily
uniprot
proteins
protein_family
Polycystin subfamily
uniprot
proteins
protein_family
Transient receptor (TC 1.A.4) family
uniprot
proteins
pubmed
11897010
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17050035
uniprot
proteins
pubmed
17208939
uniprot
proteins
pubmed
17989217
uniprot
proteins
pubmed
18794901
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23993788
uniprot
proteins
pubmed
25733853
uniprot
proteins
pubmed
27623384
uniprot
proteins
pubmed
28936784
uniprot
proteins
pubmed
29019981
uniprot
proteins
sequence_length
580
uniprot
proteins
subcellular_location
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}.
uniprot
proteins
transmembrane_region
TRANSMEM 66..86; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:29019981"; TRANSMEM 299..321; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:29019981"; TRANSMEM 351..371; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:29019981"; TRANSMEM 383..405; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:29019981"; TRANSMEM 428..448; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:29019981"; TRANSMEM 492..513; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:29019981
uniprot
proteins