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Gene and Protein Information  |
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| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 6 | 1 | 566 | 1p22.3 | MCOLN2 | mucolipin TRP cation channel 2 | 2 |
| Mouse | 6 | 1 | 566 | 3 H2 | Mcoln2 | mucolipin 2 | 2 |
| Rat | 6 | 1 | 566 | 2q44 | Mcoln2 | mucolipin TRP cation channel 2 | |
| Previous and Unofficial Names |
| MCOLN2 | mucolipin 2 | mucolipidin 2 |
| Database Links |
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| Alphafold | Q8IZK6 (Hs), Q8K595 (Mm) |
| ChEMBL Target | CHEMBL4879493 (Hs) |
| Ensembl Gene | ENSG00000153898 (Hs), ENSMUSG00000011008 (Mm), ENSRNOG00000015089 (Rn) |
| Entrez Gene | 255231 (Hs), 68279 (Mm), 292168 (Rn) |
| Human Protein Atlas | ENSG00000153898 (Hs) |
| KEGG Gene | hsa:255231 (Hs), mmu:68279 (Mm), rno:292168 (Rn) |
| OMIM | 607399 (Hs) |
| Pharos | Q8IZK6 (Hs) |
| RefSeq Nucleotide | NM_153259 (Hs), NM_026656 (Mm), NM_001005846 (Mm), NM_001039005 (Rn) |
| RefSeq Protein | NP_694991 (Hs), NP_080932 (Mm), NP_001005846 (Mm), NP_001034094 (Rn) |
| UniProtKB | Q8IZK6 (Hs), Q8K595 (Mm) |
| Wikipedia | MCOLN2 (Hs) |
| Associated Proteins |
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| Functional Characteristics |
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| Conducts Na+; monovalent cation flux suppressed by divalent cations; inwardly rectifying | |
| Ion Selectivity and Conductance Comments |
| Selectivity rank order: Na+ ~ K+ ~ Cs+ [3-4,6], Ca2+ ~Fe2+ [3] (measured using the activating mutation, A369P, of TRPML2). The plasma membrane-localised and consitutively active TRPML2 mutant (A396P), corresponding to the Va mutation in TRPML3, is a cation nonselective, ion channel [5]. This mutation is unlikely to affect the pore properties and is currently accepted as representing the wild type TRPML2 permeation properties if such data are not available for wild-type TRPML2 channels. Wild type TRPML2 appears to primarily span membranes of intracellular lysosomes and endosomes. |
| Voltage Dependence Comments |
| Strong inwardly rectifying; activation only at negative voltages. |
| Activators (Human) |
| TRPML2Va: Constitutively active, current potentiated by extracellular acidification (equivalent to intralysosomal acidification) |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Phosphatidyl (3,5) inositol bisphosphate [4], SF-21, SF-41, SF-81 [6] and ML SA1 [14] are all reported to be activators of TRPML2. In a heterologous overexpression system, TRPML2 can be weakly activated by Na+ removal followed by re-addition [6]. |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Process Associations | ||
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| Tissue Distribution
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| Functional Assays
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| Biologically Significant Variants
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| Biologically Significant Variant Comments | ||||||||||||||
| Currents have only been reported from the long splice variant (NP_080932, [5]). |
1. Curcio-Morelli C, Zhang P, Venugopal B, Charles FA, Browning MF, Cantiello HF, Slaugenhaupt SA. (2010) Functional multimerization of mucolipin channel proteins. J Cell Physiol, 222 (2): 328-35. [PMID:19885840]
2. Di Palma F, Belyantseva IA, Kim HJ, Vogt TF, Kachar B, Noben-Trauth K. (2002) Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. Proc Natl Acad Sci USA, 99 (23): 14994-9. [PMID:12403827]
3. Dong XP, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H. (2008) The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature, 455 (7215): 992-6. [PMID:18794901]
4. Dong XP, Shen D, Wang X, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman LS, Delling M et al.. (2010) PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome. Nat Commun, 1: 38. [PMID:20802798]
5. Grimm C, Cuajungco MP, van Aken AF, Schnee M, Jörs S, Kros CJ, Ricci AJ, Heller S. (2007) A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. Proc Natl Acad Sci USA, 104 (49): 19583-8. [PMID:18048323]
6. Grimm C, Jörs S, Guo Z, Obukhov AG, Heller S. (2012) Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules. J Biol Chem, 287 (27): 22701-8. [PMID:22753890]
7. Grimm C, Jörs S, Saldanha SA, Obukhov AG, Pan B, Oshima K, Cuajungco MP, Chase P, Hodder P, Heller S. (2010) Small molecule activators of TRPML3. Chem Biol, 17 (2): 135-48. [PMID:20189104]
8. Karacsonyi C, Miguel AS, Puertollano R. (2007) Mucolipin-2 localizes to the Arf6-associated pathway and regulates recycling of GPI-APs. Traffic, 8 (10): 1404-14. [PMID:17662026]
9. Lev S, Zeevi DA, Frumkin A, Offen-Glasner V, Bach G, Minke B. (2010) Constitutive activity of the human TRPML2 channel induces cell degeneration. J Biol Chem, 285 (4): 2771-82. [PMID:19940139]
10. Lindvall JM, Blomberg KE, Wennborg A, Smith CI. (2005) Differential expression and molecular characterisation of Lmo7, Myo1e, Sash1, and Mcoln2 genes in Btk-defective B-cells. Cell Immunol, 235 (1): 46-55. [PMID:16137664]
11. Plesch E, Chen CC, Butz E, Scotto Rosato A, Krogsaeter EK, Yinan H, Bartel K, Keller M, Robaa D, Teupser D et al.. (2018) Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells. Elife, 7. [PMID:30479274]
12. Rühl P, Rosato AS, Urban N, Gerndt S, Tang R, Abrahamian C, Leser C, Sheng J, Jha A, Vollmer G et al.. (2021) Estradiol analogs attenuate autophagy, cell migration and invasion by direct and selective inhibition of TRPML1, independent of estrogen receptors. Sci Rep, 11 (1): 8313. [PMID:33859333]
13. Samie MA, Grimm C, Evans JA, Curcio-Morelli C, Heller S, Slaugenhaupt SA, Cuajungco MP. (2009) The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the presence of TRPML1. Pflugers Arch, 459 (1): 79-91. [PMID:19763610]
14. Shen D, Wang X, Li X, Zhang X, Yao Z, Dibble S, Dong XP, Yu T, Lieberman AP, Showalter HD et al.. (2012) Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release. Nat Commun, 3: 731. [PMID:22415822]
15. 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. [PMID:16606612]
16. Venugopal B, Mesires NT, Kennedy JC, Curcio-Morelli C, Laplante JM, Dice JF, Slaugenhaupt SA. (2009) Chaperone-mediated autophagy is defective in mucolipidosis type IV. J Cell Physiol, 219 (2): 344-53. [PMID:19117012]
17. Zeevi DA, Lev S, Frumkin A, Minke B, Bach G. (2010) Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy. J Cell Sci, 123 (Pt 18): 3112-24. [PMID:20736310]
