MCOLN3

MCOLN3
Identifiers
Aliases	MCOLN3, TRP-ML3, TRPML3, mucolipin 3, mucolipin TRP cation channel 3
External IDs	OMIM: 607400; MGI: 1890500; HomoloGene: 10118; GeneCards: MCOLN3; OMA:MCOLN3 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p22.3 Start 85,018,082 bp End 85,048,500 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3 H2|3 71.03 cM Start 145,823,205 bp End 145,847,561 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex corpus epididymis germinal epithelium pituitary gland anterior pituitary skin of thigh body of pancreas skin of hip Top expressed in vestibular membrane of cochlear duct epithelium of small intestine stria vascularis vestibular sensory epithelium yolk sac utricle iris migratory enteric neural crest cell medullary collecting duct right kidney More reference expression data BioGPS n/a
Gene ontology Molecular function calcium channel activity lipid binding cation channel activity NAADP-sensitive calcium-release channel activity Cellular component plasma membrane membrane cytoplasm integral component of membrane autophagosome membrane lysosome lysosomal membrane endosome cytoplasmic vesicle early endosome membrane late endosome membrane Biological process inner ear auditory receptor cell differentiation ion transport locomotory behavior calcium ion transmembrane transport release of sequestered calcium ion into cytosol Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55283 171166 Ensembl ENSG00000055732 ENSMUSG00000036853 UniProt Q8TDD5 Q8R4F0 RefSeq (mRNA) NM_001253693 NM_018298 NM_134160 RefSeq (protein) NP_001240622 NP_060768 NP_598921 Location (UCSC) Chr 1: 85.02 – 85.05 Mb Chr 3: 145.82 – 145.85 Mb PubMed search
Wikidata
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Mucolipin-3 also known as TRPML3 (transient receptor potential cation channel, mucolipin subfamily, member 3) is a protein that in humans is encoded by the MCOLN3 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.

Gene

In human, the MCOLN3 gene resides on the short arm of chromosome 1 at 1p22.3. The gene is split in 12 exons, which entail the open reading frame of 1659 nucleotides. The encoded protein, TRPML3, has 553 amino acid with a predicted molecular weight of ≈64 kDa. Computational analyses of the secondary structure predict the presence of six transmembrane domains, an ion transport motif (PF00520) and a transient receptor potential motif (PS50272). In the mouse, Mcoln3, is located on the distal end of chromosome 3 at cytogenetic band qH2. Human and mouse TRPML3 proteins share 91% sequence identity. All vertebrate species, for which a genomic sequence is available, harbor the MCOLN3 gene. Homologs of MCOLN3 are also present in the genome of insects (Drosophila melanogaster), nematodes (Caenorhabditis elegans), sea urchin (Strongylocentrotus purpuratus) and lower organisms including Hydra and Dictyostelium.

Function

TRPML3 is an inwardly-rectifying cation channel.

Phenotypes

Mutations of the MCOLN3 gene in mice result in auditory hair cell death and deafness.

Ligands

Agonists (channel activators)

• ML-SA1 (non selective vs TRPML1)
• SN-2 (highly selective for TRPML3)

See also

• transient receptor potential cation channel, mucolipin subfamily, member 1 (MCOLN1)
• transient receptor potential cation channel, mucolipin subfamily, member 2 (MCOLN2)

Further reading

• Venkatachalam K, Hofmann T, Montell C (2006). "Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1". J. Biol. Chem. 281 (25): 17517–27. doi:10.1074/jbc.M600807200. PMC 4196876. PMID 16606612.
• Fares H, Greenwald I (2001). "Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog". Nat. Genet. 28 (1): 64–8. doi:10.1038/88281. PMID 11326278.
• Kim HJ, Li Q, Tjon-Kon-Sang S, et al. (2008). "A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype". EMBO J. 27 (8): 1197–205. doi:10.1038/emboj.2008.56. PMC 2367400. PMID 18369318.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Grimm C, Jörs S, Heller S (2009). "Life and Death of Sensory Hair Cells Expressing Constitutively Active TRPML3". J. Biol. Chem. 284 (20): 13823–31. doi:10.1074/jbc.M809045200. PMC 2679483. PMID 19299509.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Kim HJ, Li Q, Tjon-Kon-Sang S, et al. (2007). "Gain-of-function mutation in TRPML3 causes the mouse Varitint-Waddler phenotype". J. Biol. Chem. 282 (50): 36138–42. doi:10.1074/jbc.C700190200. PMID 17962195.
• Di Palma F, Belyantseva IA, Kim HJ, et al. (2002). "Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice". Proc. Natl. Acad. Sci. U.S.A. 99 (23): 14994–9. doi:10.1073/pnas.222425399. PMC 137533. PMID 12403827.
• Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.

External links

• MCOLN3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)