Property Summary

NCBI Gene PubMed Count 66
PubMed Score 255.59
PubTator Score 184.64

Knowledge Summary

Patent (48,723)

TINX Plot

  Disease (5)

Disease Target Count
Mucolipidoses 1
Disease Target Count Z-score Confidence
Glycoproteinosis 13 0.0 4.0
Disease Target Count Z-score Confidence
Gangliosidosis 17 7.222 3.6
Pain agnosia 99 3.002 1.5
Disease Target Count
Mucolipidosis Type IV 2
Disease Target Count
Mucolipidosis 4 1

Expression

 OMIM Phenotype (1)

Protein-protein Interaction (1)

MLP Assay (5)

AID Type Active / Inconclusive / Inactive Description
2770 screening 0 / 0 / 3 Late stage counterscreen results from the probe development effort to identify selective agonists of the Transient Receptor Potential Channels 3 (TRPML3): other ion channel Fura-2 profiling assay
624414 screening 485 / 473 / 404466 qHTS for Agonists of the Human Mucolipin Transient Receptor Potential 1 (TRPML1)
624415 screening 60 / 1763 / 388547 qHTS for Inhibitors of the Human Mucolipin Transient Receptor Potential 1 (TRPML1)
624423 summary 0 / 0 / 0 qHTS for Inhibitors of the Human Mucolipin Transient Receptor Potential 1 (TRPML1): Summary
624424 summary 0 / 0 / 0 qHTS for Agonists of the Human Mucolipin Transient Receptor Potential 1 (TRPML1): Summary

Gene RIF (46)

PMID Text
26195823 target of rapamycin (TOR), a nutrient-sensitive protein kinase that negatively regulates autophagy, directly targets and inactivates the TRPML1 channel and thereby functional autophagy, through phosphorylation
26009188 This review summarizes the current understanding of TRPML1 activation and regulation
25733853 lysosomal adaptation to environmental cues such as nutrient levels requires mTOR/TFEB-dependent, lysosome-to-nucleus regulation of lysosomal ML1 channels and Ca(2+) signaling.
24960374 TRPML1 has a novel role in protecting against lysosomotropic amine toxicity.
24192042 Retinal pigmented epithelial cells develop a punctate phenotype within 48 hours of small interfering (si)RNA-induced TRPML1-knockdown.
23685283 report of the first Saudi patient with Mucolipidosis type IV from a consanguineous family with two branches having a total of five patients carrying a novel transition mutation, c.1307A>G (p.Y436C) in exon 11
23418601 Data identified proteins as candidate TRPML1 interactors, and some false-positive interactors.
23368743 TRPML1 works in concert with ZnT4 to regulate zinc translocation between the cytoplasm and lysosomes.
23047439 Findings raise the possibility that the neurological dysfunction in patients with mucolipidosis type IV may arise from amino acid deprivation of TPRML in neurons.
22733759 PI(4,5)P(2) may serve as a negative cofactor for intracellular channels such as TRPML1
22415822 findings show that TRPML1-mediated lysosomal Ca(2 ) release is dramatically reduced in Niemann-Pick disease cells; propose that abnormal accumulation of luminal lipids causes secondary lysosome storage by blocking TRPML1- and Ca(2 )-dependent lysosomal trafficking
22262857 an acute siRNA-mediated loss of TRPML1 specifically causes a leak of lysosomal protease cathepsin B (CatB) into the cytoplasm. CatB leak is associated with apoptosis, which can be prevented by CatB inhibition.
21889421 TFEB transcriptionally regulates lysosomal exocytosis both by inducing the release of intracellular Ca2+ through its target gene MCOLN1 and by increasing the population of lysosomes ready to fuse with the plasma membrane.
21613607 NAADP increases lysosomal TRP-ML1 channel activity to release Ca(2+), which promotes the interaction of endosomes and lysosomes and thereby regulates lipid transport to lysosomes.
21540176 although TRPML1 and TPCs are present in the same complex, they function as two independent organellar ion channels and that TPCs, not TRPMLs, are the targets for NAADP.
21290297 molecular modulators of TRPML1 function may lead to novel approaches to modulating biological processes that depend on the endocytic pathway such as growth factor signaling
21256127 mucolipin-1 contributes to membrane remodeling through a serine lipase consensus domain, and thus represents a novel type of bifunctional protein.
21224396 Two members of the lysosome associated protein transmembrane (LAPTM) family were identified as novel interaction partners of mucolipin 1 (MCOLN1)
20864526 the loss of TRPML1 function results in intracellular chelatable zinc dyshomeostasis.
20736310 TRPML 1, 2 and 3 assemblies regulated cell viability and starvation-induced autophagy.
19885840 Data show that TRPMLs form distinct functional channel complexes.
19864416 ALG-2 acts as a Ca(2+) sensor that modulates the function of MCOLN1 along the late endosomal-lysosomal pathway.
19763610 TRPML1 appears to play a novel role in the tissue-specific transcriptional regulation of TRPML2.
19638346 Mutations of the TRPML1 is associated with activation of the channel.
19006653 a Turkish patient who, in addition to the typical characteristics of mucolipidosis type IV, defects in internal capsule, micrognathia and clinodactyly of the fifth fingers. DNA sequencing revealed a novel homozygous c.1364C>T (S456L) mutation in MCOLN1.
18794901 TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes
18504305 Effects of TRP-ML1 loss on hydrolytic activity have a cumulative effect on lysosome function, resulting in a lag between TRP-ML1 loss and full manifestation of mucolipidosis type IV.[TRP-ML1]
18264947 Observational study of genotype prevalence. (HuGE Navigator)
17988215 tTwo PKA (protein kinase A) consensus motifs in the C-terminal tail of MCOLN1, containing Ser(557) and Ser(559). Ser(557) are the principal phosphorylation sites.
17306511 Mutations in the gene coding for TRPML1 result in a lysosomal storage disorder (LSD).
17239335 Sequencing of the MCOLN1 gene identified compound heterozygosity for D362Y and A-->T transition leading to the creation of a novel donor splicing site and a 4-bp deletion from exon 13 at the mRNA level.
16978393 Data demonstrate that the correct localization of mucolipin-1 and the integrity of its ion pore are essential for its physiological function in the late endocytic pathway.
16645217 Observational study of genotype prevalence. (HuGE Navigator)
16606612 there is a hierarchy controlling the subcellular distributions of the TRPMLs such that TRPML1 and TRPML2 dictate the localization of TRPML3 and not vice versa
16517607 posttranslational processing of ML1 is more complex than previously described and this protein is delivered to lysosomes primarily via an AP-1-dependent route that does not involve passage via the cell surface
16361256 TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity
16287144 Observational study of genotype prevalence. (HuGE Navigator)
16257972 TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage
16133264 ML1 may help regulate vesicular membrane potential, the process of acidification associated with normal vesicular function, and/or Ca2+ transport, into intracellular organelles.
15336987 A review of mucolipin-1's role in calcium signaling and membrane trafficking in mucolipidosis IV.
15070744 Transfected into Caenorhabditis elegans affects lysosome biogenesis.
12459486 Characterization of the conductance properties of mucolipin-1 in the presence of cations.
12125810 Review of mutations in MCOLN1 that lead to Mucolipidosis Type IV
11845410 Observational study of genotype prevalence. (HuGE Navigator)
11845410 Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish population from New York metropolitan area
11317355 Observational study of genotype prevalence. (HuGE Navigator)

AA Sequence

MTAPAGPRGSETERLLTPNPGYGTQAGPSPAPPTPPEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLMLQV      1 - 70
VKILVVTVQLILFGLSNQLAVTFREENTIAFRHLFLLGYSDGADDTFAAYTREQLYQAIFHAVDQYLALP     71 - 140
DVSLGRYAYVRGGGDPWTNGSGLALCQRYYHRGHVDPANDTFDIDPMVVTDCIQVDPPERPPPPPSDDLT    141 - 210
LLESSSSYKNLTLKFHKLVNVTIHFRLKTINLQSLINNEIPDCYTFSVLITFDNKAHSGRIPISLETQAH    211 - 280
IQECKHPSVFQHGDNSFRLLFDVVVILTCSLSFLLCARSLLRGFLLQNEFVGFMWRQRGRVISLWERLEF    281 - 350
VNGWYILLVTSDVLTISGTIMKIGIEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFFHNYNILIATLRV    351 - 420
ALPSVMRFCCCVAVIYLGYCFCGWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVTFAAMQAQQGRSSLV    421 - 490
WLFSQLYLYSFISLFIYMVLSLFIALITGAYDTIKHPGGAGAEESELQAYIAQCQDSPTSGKFRRGSGSA    491 - 560
CSLLCCCGRDPSEEHSLLVN                                                      561 - 580
//

Text Mined References (67)

PMID Year Title
26195823 2015 The mucolipidosis IV Ca2+ channel TRPML1 (MCOLN1) is regulated by the TOR kinase.
26009188 2015 Regulation of TRPML1 function.
25733853 2015 Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation.
24960374 2014 A novel role of transient receptor potential mucolipin1 (TRPML1) in protecting against imidazole-induced cytotoxicity.
24192042 2014 Loss of TRPML1 promotes production of reactive oxygen species: is oxidative damage a factor in mucolipidosis type IV?
23685283 2013 A novel mutation in a large family causes a unique phenotype of Mucolipidosis IV.
23418601 2013 Systematic screens for proteins that interact with the mucolipidosis type IV protein TRPML1.
23382219 2013 Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
23368743 2013 Zinc-dependent lysosomal enlargement in TRPML1-deficient cells involves MTF-1 transcription factor and ZnT4 (Slc30a4) transporter.
23047439 2013 Feast or famine: role of TRPML in preventing cellular amino acid starvation.
22733759 2012 Phosphoinositide isoforms determine compartment-specific ion channel activity.
22415822 2012 Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release.
22262857 2012 Loss of lysosomal ion channel transient receptor potential channel mucolipin-1 (TRPML1) leads to cathepsin B-dependent apoptosis.
21889421 2011 Transcriptional activation of lysosomal exocytosis promotes cellular clearance.
21613607 2011 Reconstitution of lysosomal NAADP-TRP-ML1 signaling pathway and its function in TRP-ML1(-/-) cells.
21540176 2011 Transient receptor potential mucolipin 1 (TRPML1) and two-pore channels are functionally independent organellar ion channels.
21290297 2011 TRPML1.
21256127 2011 The cation channel mucolipin-1 is a bifunctional protein that facilitates membrane remodeling via its serine lipase domain.
21224396 2011 LAPTMs regulate lysosomal function and interact with mucolipin 1: new clues for understanding mucolipidosis type IV.
20864526 2010 Zinc dyshomeostasis is linked with the loss of mucolipidosis IV-associated TRPML1 ion channel.
20736310 2010 Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy.
19885840 2010 Functional multimerization of mucolipin channel proteins.
19864416 2009 Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1.
19763610 2009 The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the presence of TRPML1.
19638346 2009 Activating mutations of the TRPML1 channel revealed by proline-scanning mutagenesis.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19006653 2009 Mucolipidosis type IV in a Turkish boy associated with a novel MCOLN1 mutation.
18794901 2008 The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.
18504305 2008 Membrane traffic and turnover in TRP-ML1-deficient cells: a revised model for mucolipidosis type IV pathogenesis.
18264947 2008 Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: should the rationale for mutation choice for screening be reevaluated?
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17988215 2008 Mucolipin 1 channel activity is regulated by protein kinase A-mediated phosphorylation.
17924347 2007 Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IV.
17897319 2007 Integral and associated lysosomal membrane proteins.
17306511 2007 TRPML and lysosomal function.
17239335 2007 Mucolipidosis IV: report of a case with ocular restricted phenotype caused by leaky splice mutation.
16978393 2006 Mucolipin-1 is a lysosomal membrane protein required for intracellular lactosylceramide traffic.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16645217 2006 Rapid one-step carrier detection assay of mucolipidosis IV mutations in the Ashkenazi Jewish population.
16606612 2006 Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1.
16517607 2006 Posttranslational cleavage and adaptor protein complex-dependent trafficking of mucolipin-1.
16382100 2005 International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels.
16361256 2006 TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity.
16287144 2005 The frequency of mucolipidosis type IV in the Ashkenazi Jewish population and the identification of 3 novel MCOLN1 mutations.
16257972 2005 TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage.
16133264 2005 Cation channel activity of mucolipin-1: the effect of calcium.
15523648 2004 Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15345747 2004 Phosphoproteomic analysis of the developing mouse brain.
15336987 2004 Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IV.
15178326 2004 Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization.
15070744 2004 Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis.
14749347 2004 Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12459486 2002 Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway.
12182165 2002 The neurogenetics of mucolipidosis type IV.
12125810 2002 The molecular basis of mucolipidosis type IV.
11326278 2001 Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog.
11318610 2001 A physical and transcript map of the MCOLN1 gene region on human chromosome 19p13.3-p13.2.
11317355 2001 Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population.
11030752 2000 Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.
11013137 2000 Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV.
10973263 2000 Identification of the gene causing mucolipidosis type IV.
10441585 1999 Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
2874839 1986 Receptor-mediated endocytosis: the intracellular journey of transferrin and its receptor.