Mcoln3
entrez
171166
canonical
uniprot
Q8R4F0
canonical
ensembl
ENSMUSG00000036853
resolver
ensp
ENSMUSP00000038801
resolver
enst
ENSMUST00000039450
resolver
genesymbol
Mcoln3
resolver
uniprot
Q3KP78
resolver
uniprot
Q8BS73
resolver
uniprot
Q8BSG1
resolver
uniprot
Q8CDB2
resolver
uniprot_entry
MCLN3_MOUSE
resolver
uniprot_entry
Q3KP78_MOUSE
resolver
uniprot_sec
Q8BS73
resolver
uniprot_sec
Q8BSG1
resolver
uniprot_sec
Q8CDB2
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(+). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+) (By similarity). {ECO:0000250|UniProtKB:F6RG56, ECO:0000250|UniProtKB:Q8TDD5}.
uniprot
proteins
amino_acid_sequence
MANPEVLVSSCRARQDESPCTFHPSSSPSEQLLLEDQMRRKLKFFFMNPCEKFWARGRKPWKLAIQILKIAMVTIQLVLFGLSNQMVVAFKEENTIAFKHLFLKGYMDRMDDTYAVYTQSEVYDQIIFAVTQYLQLQNISVGNHAYENKGTKQSAMAICQHFYRQGTICPGNDTFDIDPEVETECFLVEPDEASHLGTPGENKLNLSLDFHRLLTVELQFKLKAINLQTVRHQELPDCYDFTLTITFDNKAHSGRIKISLDNDISIKECKDWHVSGSIQKNTHYMMIFDAFVILTCLASLVLCARSVIRGLQLQQEFVNFFLLHYKKEVSASDQMEFINGWYIMIIISDILTIVGSVLKMEIQAKSLTSYDVCSILLGTSTMLVWLGVIRYLGFFAKYNLLILTLQAALPNVMRFCCCAAMIYLGYCFCGWIVLGPYHEKFRSLNRVSECLFSLINGDDMFSTFAKMQQKSYLVWLFSRVYLYSFISLFIYMILSLFIALITDTYETIKHYQQDGFPETELRKFIAECKDLPNSGKYRLEDDPPGSLLCCCKK
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Mcoln3 are the cause of the varitin-waddler (Va) phenotype. Classical Va mice exhibit early-onset hearing loss, vestibular defects, pigmentation abnormalities and perinatal lethality. The phenotype varitin-waddler Jackcon (Va-J), which arose in a cross segregating for Va, is similar but less severe. {ECO:0000269|PubMed:12403827, ECO:0000269|PubMed:18048323}.
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:17989217). 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 (By similarity). Also permeable to Mg(2+), Na(+) and K(+) (PubMed:17989217). 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 (PubMed:18801844). Involved in the regulation of autophagy. Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (PubMed:24269818). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events. Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (By similarity). {ECO:0000250|UniProtKB:Q8TDD5, ECO:0000269|PubMed:17989217, ECO:0000269|PubMed:18801844, ECO:0000269|PubMed:24269818}.
uniprot
proteins
mass_dalton
63748
uniprot
proteins
mutagenesis
MUTAGEN 458..459; /note="DD->KK: Abolishes channel activity."; /evidence="ECO:0000269|PubMed:17989217
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8TDD5}.
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
12403827
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17989217
uniprot
proteins
pubmed
18048323
uniprot
proteins
pubmed
18801844
uniprot
proteins
pubmed
21179200
uniprot
proteins
pubmed
24269818
uniprot
proteins
sequence_length
553
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Early endosome membrane {ECO:0000250|UniProtKB:Q8TDD5}; Multi-pass membrane protein {ECO:0000250|UniProtKB:F6RG56}. Late endosome membrane {ECO:0000269|PubMed:17989217}; Multi-pass membrane protein {ECO:0000250|UniProtKB:F6RG56}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:24269818}; Multi-pass membrane protein {ECO:0000250|UniProtKB:F6RG56}. Cell projection, stereocilium membrane {ECO:0000269|PubMed:18801844}; Multi-pass membrane protein {ECO:0000250|UniProtKB:F6RG56}. Note=Recycles between the plasma membrane and intracellular compartments by a dynamin-dependent endocytic pathway (By similarity). In the cochlea located at the base of stereocilia near the position of the ankle links. {ECO:0000250|UniProtKB:Q8TDD5, ECO:0000269|PubMed:18801844}.
uniprot
proteins
transmembrane_region
TRANSMEM 63..83; /note="Helical"; /evidence="ECO:0000250|UniProtKB:F6RG56"; TRANSMEM 284..304; /note="Helical"; /evidence="ECO:0000250|UniProtKB:F6RG56"; TRANSMEM 342..362; /note="Helical"; /evidence="ECO:0000250|UniProtKB:F6RG56"; TRANSMEM 372..392; /note="Helical"; /evidence="ECO:0000250|UniProtKB:F6RG56"; TRANSMEM 415..435; /note="Helical"; /evidence="ECO:0000250|UniProtKB:F6RG56"; TRANSMEM 476..497; /note="Helical"; /evidence="ECO:0000250|UniProtKB:F6RG56
uniprot
proteins