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FLASH GENE

Symbol

MCOLN3

contributors: mct/pgu - updated : 24-03-2016

HGNC name	mucolipin 3
HGNC id	13358

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_018298 13 - 2813 NP_060768 - 553 - 2006 16606612 NM_001253693 12 - 2699 NP_001240622 - 497 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     lowly Hearing/Equilibrium ear inner cochlea   highly Homo sapiens Lymphoid/Immune spleen           thymus         nervous brain diencephalon       Skin/Tegument skin         Urinary kidney         Homo sapiens Visual eye

cells

System Cell Pubmed Species Stage Rna symbol Hearing / Equilibrium cochlea cell Nervous neuron Skin/Tegument melanocyte

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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