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MCOLN3
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<h2 id="gene">Gene</h2> <p>In human, the <i>MCOLN3</i> gene resides on the short arm of <a href="/facts/Chromosome_1/2ujmYz2w">chromosome 1</a> at 1p22.3. The gene is split in 12 <a href="/facts/Exons/8KWJtLuN">exons</a>, which entail the <a href="/facts/Open_reading_frame/Saams83e">open reading frame</a> of 1659 nucleotides. The encoded protein, TRPML3, has 553 amino acid with a predicted molecular weight of ≈64 <a href="/facts/KDa/IMATU3vf">kDa</a>. Computational analyses of the secondary structure predict the presence of six <a href="/facts/Transmembrane_domain/D1j0PwSR">transmembrane domains</a>, an ion transport motif (PF00520) and a <a href="/facts/Transient_receptor_potential_channel/bbJSljzL">transient receptor potential</a> motif (PS50272). In the mouse, <i>Mcoln3</i>, is located on the distal end of <a href="/facts/Chromosome_3/2lHrRbHd">chromosome 3</a> at cytogenetic band qH2. Human and mouse TRPML3 proteins share 91% sequence identity.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> All vertebrate species, for which a genomic sequence is available, harbor the <i>MCOLN3</i> gene. Homologs of <i>MCOLN3</i> are also present in the genome of insects (<i><a href="/facts/Drosophila_melanogaster/KtnHVCcB">Drosophila melanogaster</a></i>), nematodes (<i><a href="/facts/Caenorhabditis_elegans/XJVJzPn2">Caenorhabditis elegans</a></i>), sea urchin (<i><a href="/facts/Strongylocentrotus_purpuratus/VC3Iwcr6">Strongylocentrotus purpuratus</a></i>) and lower organisms including Hydra and Dictyostelium. </p> <h2 id="expression">Expression</h2> <h2 id="function">Function</h2> <p>TRPML3 is an inwardly-rectifying <a href="/facts/Ion/3bePpDna">cation</a> <a href="/facts/Ion_channel/A46LARFH">channel</a>.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="genetics">Genetics</h2> <h2 id="phenotypes">Phenotypes</h2> <p>Mutations of the MCOLN3 gene in mice result in auditory <a href="/facts/Hair_cell/dWUGGF0t">hair cell</a> death and <a href="/facts/Deafness/PT2xcLaX">deafness</a>.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <h2 id="ligands">Ligands</h2> Agonists (channel activators) <ul><li><a href="/facts/ML-SA1/lMSzPQXJ">ML-SA1</a> (non selective vs <a href="/facts/TRPML1/tJNypJqG">TRPML1</a>)</li> <li><a href="/facts/SN-2/Woe8Lfy1">SN-2</a> (highly selective for TRPML3)</li></ul> <h2 id="see-also">See also</h2> <ul><li>transient receptor potential cation channel, mucolipin subfamily, member 1 (<a href="/facts/MCOLN1/tJNypJqG">MCOLN1</a>)</li> <li>transient receptor potential cation channel, mucolipin subfamily, member 2 (<a href="/facts/MCOLN2/nRARhXb8">MCOLN2</a>)</li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Venkatachalam K, Hofmann T, Montell C (2006). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196876">"Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1"</a>. <i>J. Biol. Chem</i>. 281 (25): 17517–27. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M600807200">10.1074/jbc.M600807200</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196876">4196876</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16606612">16606612</a>.</li> <li>Fares H, Greenwald I (2001). "Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog". <i>Nat. Genet</i>. 28 (1): 64–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F88281">10.1038/88281</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11326278">11326278</a>.</li> <li>Kim HJ, Li Q, Tjon-Kon-Sang S, et al. (2008). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367400">"A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype"</a>. <i>EMBO J</i>. 27 (8): 1197–205. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Femboj.2008.56">10.1038/emboj.2008.56</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367400">2367400</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/18369318">18369318</a>.</li> <li>Ota T, Suzuki Y, Nishikawa T, et al. (2004). <a href="https://doi.org/10.1038%2Fng1285">"Complete sequencing and characterization of 21,243 full-length human cDNAs"</a>. <i>Nat. Genet</i>. 36 (1): 40–5. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fng1285">10.1038/ng1285</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/14702039">14702039</a>.</li> <li>Grimm C, Jörs S, Heller S (2009). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679483">"Life and Death of Sensory Hair Cells Expressing Constitutively Active TRPML3"</a>. <i>J. Biol. Chem</i>. 284 (20): 13823–31. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M809045200">10.1074/jbc.M809045200</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679483">2679483</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/19299509">19299509</a>.</li> <li>Strausberg RL, Feingold EA, Grouse LH, et al. (2002). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139241">"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 99 (26): 16899–903. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2002PNAS...9916899M">2002PNAS...9916899M</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.242603899">10.1073/pnas.242603899</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139241">139241</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12477932">12477932</a>.</li> <li>Kim HJ, Li Q, Tjon-Kon-Sang S, et al. (2007). <a href="https://doi.org/10.1074%2Fjbc.C700190200">"Gain-of-function mutation in TRPML3 causes the mouse Varitint-Waddler phenotype"</a>. <i>J. Biol. Chem</i>. 282 (50): 36138–42. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.C700190200">10.1074/jbc.C700190200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17962195">17962195</a>.</li> <li><a href="/facts/Federica_Di_Palma/d2d25WoP">Di Palma F</a>, Belyantseva IA, Kim HJ, et al. (2002). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137533">"Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 99 (23): 14994–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.222425399">10.1073/pnas.222425399</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137533">137533</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12403827">12403827</a>.</li> <li>Gregory SG, Barlow KF, McLay KE, et al. (2006). <a href="https://doi.org/10.1038%2Fnature04727">"The DNA sequence and biological annotation of human chromosome 1"</a>. <i>Nature</i>. 441 (7091): 315–21. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2006Natur.441..315G">2006Natur.441..315G</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fnature04727">10.1038/nature04727</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16710414">16710414</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=MCOLN3+protein%2C+human">MCOLN3+protein,+human</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Noben-Trauth K (January 2011). "Chapter 13: TRPML3". In Islam MS (ed.). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700. ISBN 978-94-007-0264-6. <a href="978-94-007-0264-6" target="_blank">978-94-007-0264-6</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Noben-Trauth, Konrad (2011). "The TRPML3 Channel: From Gene to Function". Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. pp. 229–237. doi:10.1007/978-94-007-0265-3_13. ISBN 978-94-007-0264-6. PMID 21290299. <a href="978-94-007-0264-6" target="_blank">978-94-007-0264-6</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Nagata K, Zheng L, Madathany T, Castiglioni AJ, Bartles JR, García-Añoveros J (January 2008). "The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration". Proc. Natl. Acad. Sci. U.S.A. 105 (1): 353–8. Bibcode:2008PNAS..105..353N. doi:10.1073/pnas.0707963105. PMC 2224216. PMID 18162548. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2224216" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2224216</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> </ol>