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FLASH GENE
Symbol MCOLN3 contributors: mct/pgu - updated : 24-03-2016
HGNC name mucolipin 3
HGNC id 13358
Location 1p22.3      Physical location : 85.483.765 - 85.514.169
Synonym symbol(s) FLJ11006, MGC71509, FLJ36629, TRP-ML3, TRPML3
DNA
TYPE functioning gene
STRUCTURE 30.82 kb     13 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
FLJ23033 1p22.3 hypothetical protein FLJ23033 PRKACB 1p36.1or protein kinase, cAMP-dependent, catalytic, beta LOC148418 1p22.3 dnaj-like protein LOC391051 1 similar to urate oxidase (EC 1.7.3.3) - baboon DLAD 1p31.1 similar to urate oxidase (EC 1.7.3.3) - baboon RPF1 1p22.3 similar to urate oxidase (EC 1.7.3.3) - baboon GNG5 1p22 guanine nucleotide binding protein (G protein), gamma 5 SPATA1 1p22.3 spermatogenesis associated 1 CTBS 1p22 chitobiase, di-N-acetyl- FLJ35487 1p22.3 hypothetical protein FLJ35487 SSX2IP 1p22 synovial sarcoma, X breakpoint 2 interacting protein EDG7 1p22.3-p31.1 endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 7 MCOLN2 1p22 mucolipin 2 MCOLN3 1p22.3 mucolipin 3 NYD-SP29 1p22.3 testis development protein NYD-SP29 FLJ13815 1p22.3 hypothetical protein FLJ13815 gm117 1p22.3 gm117 BCL10 1p22 B-cell CLL/lymphoma 10 DDAH1 1p22 dimethylarginine dimethylaminohydrolase 1 CYR61 1p31.p22 cysteine-rich, angiogenic inducer, 61 FLJ20729 1p22.3 hypothetical protein FLJ20729 COL24A1 1p22.3-p22.2 collagen, type XXIV, alpha 1 KIAA1229 1p22.3 KIAA1229 protein CLCA2 1p31-p22 chloride channel, calcium activated, family member 2 CLCA1 1p31-p22 chloride channel, calcium activated, family member 1 CLCA4 1p31-p22 chloride channel, calcium activated, family member 4 CLCA3 1p31-p22 chloride channel, calcium activated, family member 3
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
13 - 2813 - 553 - 2006 16606612
12 - 2699 - 497 - -
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinesmall intestine  lowly
Hearing/Equilibriumearinnercochlea highly Homo sapiens
Lymphoid/Immunespleen    
 thymus    
nervousbraindiencephalon   
Skin/Tegumentskin    
Urinarykidney     Homo sapiens
Visualeye    
cells
SystemCellPubmedSpeciesStageRna symbol
Hearing / Equilibriumcochlea cell
Nervousneuron
Skin/Tegumentmelanocyte
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six predicted transmembrane domains
  • intracellular N- and C-terminus regions
  • HOMOLOGY
    interspecies ortholog to murine Mcoln3
    ortholog to rattus Mcoln3_predicted
    Homologene
    FAMILY
  • mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels
  • polycystin subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • homomultimers are in the endoplasmic reticulum, but, localizes to lysosomes when coexpressed with either MCOLN11 or MCOLN2
  • primarily localizes to early and late endosomes in human epithelial cells
  • localizes to the plasmamembrane and to early- and late-endosomes as well as lysosomes
  • basic FUNCTION
  • might play a role in melanosome trafficking and hair cell maturation
  • Ca(2+)-permeable channel and its activity is regulated by pH
  • is a novel Ca(2+) channel that plays a crucial role in the regulation of cargo trafficking along the endosomal pathway
  • with MCOLN2, might participate with native MCOLN1 in a dynamic form of lysosomal regulation
  • pH-regulated Ca2+ channel that localizes to the endosomal pathway
  • plays an important role in the regulation of endosomal function
  • prominent role for MCOLN3 in regulating Ca2+ homeostasis at the endosomal pathway and confirm the importance of luminal Ca2+ for proper acidification and membrane fusion
  • may regulate the acidification of early endosomes, hence playing a critical role in the endocytic pathway
  • MCOLN2 and MCOLN3 are nonselective cation channels
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text membrane trafficking along endolysosomal pathways, autophagy, possible hair cell function
    PATHWAY
    metabolism
    signaling
    a component
  • MCOLN3 and TRPV5 associate to form a novel heteromeric ion channel
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • selectivity for ions Na+, K+, Ca2+, Mg2+
  • protein
  • interacting with MCOLN1, MCOLN2
  • MCOLN3 and TRPV5 associate to form a novel heteromeric ion channel
  • MCOLN3 and MCOLN3-loop specifically bind to GABARAPL2 and interaction facilitates the function of GABARAPL2 in autophagosome formation, but was not required for MCOLN3 trafficking to autophagosomes
  • cell & other
    REGULATION
    activated by Na+ removal followed by re-addition
    exposing it first to sodium-free extracellular solution and subsequently to high extracellular sodium
    inhibited by verapamil, Gd3+, extracellular or luminal low pH
    Other regulated by MCOLN1, MCOLN2 (dictate the localization of MCOLN3 and not vice versa)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    causes severe alterations in the endosomal pathway, including enlargement and clustering of endosomes, delayed epidermal growth factor receptor degradation, and impaired autophagosome maturation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • for hereditary and/or sporadic forms of neurosensory disorders
  • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mutations in the Trpml3 (Mcoln3) gene cause the varitint-waddler mouse phenotypes, exhibiting a spectrum of disease phenotypes from diluted coat color to auditory and vestibular problems
  • neonatal enterocytes of mice lacking both mucolipins (Trpml3-/-;Trpml1-/-) vacuolated pathologically within hours of birth and remained so until weaning