MCOLN3
entrez
55283
canonical
uniprot
Q8TDD5
canonical
ensembl
ENSG00000055732
resolver
ensp
ENSP00000342698
resolver
ensp
ENSP00000359621
resolver
ensp
ENSP00000559347
resolver
ensp
ENSP00000703108
resolver
genesymbol
MCOLN3
resolver
hgnc
HGNC:13358
resolver
uniprot
Q5T4H5
resolver
uniprot
Q5T4H6
resolver
uniprot
Q9NV09
resolver
uniprot_entry
MCLN3_HUMAN
resolver
uniprot_sec
Q5T4H5
resolver
uniprot_sec
Q5T4H6
resolver
uniprot_sec
Q9NV09
resolver
activity_regulation
ACTIVITY REGULATION: Channel activity is activated by PtdIns(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) (By similarity). Inhibited by lumenal H(+) and Na(+) (PubMed:18369318, PubMed:29106414). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+) (PubMed:20378547). {ECO:0000250|UniProtKB:F6RG56, ECO:0000269|PubMed:18369318, ECO:0000269|PubMed:20378547, ECO:0000269|PubMed:29106414}.
uniprot
proteins
amino_acid_sequence
MADPEVVVSSCSSHEEENRCNFNQQTSPSEELLLEDQMRRKLKFFFMNPCEKFWARGRKPWKLAIQILKIAMVTIQLVLFGLSNQMVVAFKEENTIAFKHLFLKGYMDRMDDTYAVYTQSDVYDQLIFAVNQYLQLYNVSVGNHAYENKGTKQSAMAICQHFYKRGNIYPGNDTFDIDPEIETECFFVEPDEPFHIGTPAENKLNLTLDFHRLLTVELQFKLKAINLQTVRHQELPDCYDFTLTITFDNKAHSGRIKISLDNDISIRECKDWHVSGSIQKNTHYMMIFDAFVILTCLVSLILCIRSVIRGLQLQQEFVNFFLLHYKKEVSVSDQMEFVNGWYIMIIISDILTIIGSILKMEIQAKSLTSYDVCSILLGTSTMLVWLGVIRYLGFFAKYNLLILTLQAALPNVIRFCCCAAMIYLGYCFCGWIVLGPYHDKFRSLNMVSECLFSLINGDDMFATFAKMQQKSYLVWLFSRIYLYSFISLFIYMILSLFIALITDTYETIKQYQQDGFPETELRTFISECKDLPNSGKYRLEDDPPVSLFCCCKK
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q8R4F0, ECO:0000269|PubMed:18369318, ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758, ECO:0000269|PubMed:19885840, ECO:0000269|PubMed:20378547, ECO:0000269|PubMed:21245134, ECO:0000269|PubMed:23469151, ECO:0000269|PubMed:29106414, ECO:0000305}.
uniprot
proteins
mass_dalton
64248
uniprot
proteins
mutagenesis
MUTAGEN 108; /note="D->N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-111 and N-112."; /evidence="ECO:0000269|PubMed:29106414"; MUTAGEN 111; /note="D->N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-112."; /evidence="ECO:0000269|PubMed:29106414"; MUTAGEN 112; /note="D->N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-111."; /evidence="ECO:0000269|PubMed:29106414"; MUTAGEN 252; /note="H->A: Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283."; /evidence="ECO:0000269|PubMed:18369318"; MUTAGEN 273; /note="H->A: Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283."; /evidence="ECO:0000269|PubMed:18369318"; MUTAGEN 283; /note="H->A: Constitutive active channel; abolishes inhibition by lumenal H(+); retains the Ca(2+)-dependent inactivation of the Ca(2+) current. Decreases inhibition by lumenal H(+); when associated with A-252. Decreases inhibition by lumenal H(+); when associated with A-273."; /evidence="ECO:0000269|PubMed:18369318"; MUTAGEN 283; /note="H->R: Increases inhibition by lumenal H(+)."; /evidence="ECO:0000269|PubMed:18369318"; MUTAGEN 419; /note="A->P: Constitutive active channel; abolishes inhibition by lumenal H(+); increases the pore diameter."; /evidence="ECO:0000269|PubMed:18369318, ECO:0000269|PubMed:20378547"; MUTAGEN 423; /note="Y->A: Nearly abolishes channel activation by a synthetic agonist."; /evidence="ECO:0000269|PubMed:29106414"; MUTAGEN 449; /note="E->A: Constitutive active channel; greatly impairs inhibition by lumenal Na(+)."; /evidence="ECO:0000269|PubMed:20378547"; MUTAGEN 449; /note="E->K: Abolishes channel activity."; /evidence="ECO:0000269|PubMed:20378547"; MUTAGEN 458..459; /note="DD->KK: Enhances endocytosis."; /evidence="ECO:0000269|PubMed:19522758"; MUTAGEN 458; /note="D->K: Nearly abolishes channel activity; inhibits starvation-induced autophagy."; /evidence="ECO:0000269|PubMed:19522758"; MUTAGEN 459; /note="D->A: Decreases in Ca(2+) permeability and selectivity; decreases channel pore dynamic behavior."; /evidence="ECO:0000269|PubMed:20378547"; MUTAGEN 497; /note="F->A: Nearly abolishes channel activation by a synthetic agonist."; /evidence="ECO:0000269|PubMed:29106414
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:19885840}.
uniprot
proteins
protein_family
MCOLN3 sub-subfamily
uniprot
proteins
protein_family
Polycystin subfamily
uniprot
proteins
protein_family
Transient receptor (TC 1.A.4) family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
18369318
uniprot
proteins
pubmed
19497048
uniprot
proteins
pubmed
19522758
uniprot
proteins
pubmed
19885840
uniprot
proteins
pubmed
20378547
uniprot
proteins
pubmed
21245134
uniprot
proteins
pubmed
23469151
uniprot
proteins
pubmed
29106414
uniprot
proteins
sequence_length
553
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19522758, ECO:0000269|PubMed:29106414}; Multi-pass membrane protein {ECO:0000269|PubMed:29106414}. Early endosome membrane {ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758}; Multi-pass membrane protein {ECO:0000269|PubMed:29106414}. Late endosome membrane {ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758}; Multi-pass membrane protein {ECO:0000269|PubMed:29106414}. Lysosome membrane {ECO:0000269|PubMed:19522758}; Multi-pass membrane protein {ECO:0000269|PubMed:29106414}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:19522758}. Note=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). {ECO:0000250|UniProtKB:Q8R4F0, ECO:0000269|PubMed:19522758}.
uniprot
proteins
transmembrane_region
TRANSMEM 63..83; /note="Helical"; /evidence="ECO:0000269|PubMed:29106414"; TRANSMEM 284..304; /note="Helical"; /evidence="ECO:0000269|PubMed:29106414"; TRANSMEM 342..362; /note="Helical"; /evidence="ECO:0000269|PubMed:29106414"; TRANSMEM 372..392; /note="Helical"; /evidence="ECO:0000269|PubMed:29106414"; TRANSMEM 415..435; /note="Helical"; /evidence="ECO:0000269|PubMed:29106414"; TRANSMEM 476..497; /note="Helical"; /evidence="ECO:0000269|PubMed:29106414
uniprot
proteins