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target has curated data in GtoImmuPdb
Target id: 498
Nomenclature: TRPM6
Family: Transient Receptor Potential channels (TRP), ChaK subfamily
Gene and Protein Information | |||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 6 | 1 | 2022 | 9q21.13 | TRPM6 | transient receptor potential cation channel subfamily M member 6 | 1,6,9 |
Mouse | 6 | 1 | 2028 | 19 B | Trpm6 | transient receptor potential cation channel, subfamily M, member 6 | 8 |
Rat | 6 | 1 | 2020 | 1q43 | Trpm6 | transient receptor potential cation channel, subfamily M, member 6 |
Previous and Unofficial Names |
HOMG | HSH | hypomagnesemia, secondary hypocalcemia | Channel kinase 2 | ChaK2 | Melastatin-related TRP cation channel 6 | transient receptor potential cation channel |
Database Links | |
Alphafold | Q9BX84 (Hs), Q8CIR4 (Mm) |
CATH/Gene3D | 1.20.5.1010 |
ChEMBL Target | CHEMBL1628470 (Hs) |
Ensembl Gene | ENSG00000119121 (Hs), ENSMUSG00000024727 (Mm), ENSRNOG00000013053 (Rn) |
Entrez Gene | 140803 (Hs), 225997 (Mm), 293874 (Rn) |
Human Protein Atlas | ENSG00000119121 (Hs) |
KEGG Gene | hsa:140803 (Hs), mmu:225997 (Mm), rno:293874 (Rn) |
OMIM | 607009 (Hs) |
Orphanet | ORPHA120301 (Hs) |
Pharos | Q9BX84 (Hs) |
RefSeq Nucleotide | NM_017662 (Hs), NM_153417 (Mm) |
RefSeq Protein | NP_060132 (Hs), NP_700466 (Mm) |
UniProtKB | Q9BX84 (Hs), Q8CIR4 (Mm) |
Wikipedia | TRPM6 (Hs) |
Associated Proteins | ||||||||||||||||||||
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Ion Selectivity and Conductance | ||||||
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Other chemical activators (Human) |
constitutively active, activated by reduction of intracellular Mg2+ |
Download all structure-activity data for this target as a CSV file
Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TRPM6 is also activated by low pH [3]. |
Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DiscoveRx KINOMEscan® screen | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 2,10 |
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Target used in screen: TRPM6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
Expressed on mouse B cells [5]. |
Tissue Distribution | ||||||||
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Functional Assays | ||||||||||
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||||||||||||||||||||||||||||
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1. Chubanov V, Waldegger S, Mederos y Schnitzler M, Vitzthum H, Sassen MC, Seyberth HW, Konrad M, Gudermann T. (2004) Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc Natl Acad Sci USA, 101 (9): 2894-9. [PMID:14976260]
2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
3. Li M, Jiang J, Yue L. (2006) Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. J Gen Physiol, 127 (5): 525-37. [PMID:16636202]
4. Nie M, Bal MS, Liu J, Yang Z, Rivera C, Wu XR, Hoenderop JGJ, Bindels RJM, Marciano DK, Wolf MTF. (2018) Uromodulin regulates renal magnesium homeostasis through the ion channel transient receptor potential melastatin 6 (TRPM6). J Biol Chem, 293 (42): 16488-16502. [PMID:30139743]
5. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br J Pharmacol, 173 (6): 953-69. [PMID:26603538]
6. Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D et al.. (2002) Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet, 31 (2): 166-70. [PMID:12032568]
7. Schmitz C, Dorovkov MV, Zhao X, Davenport BJ, Ryazanov AG, Perraud AL. (2005) The channel kinases TRPM6 and TRPM7 are functionally nonredundant. J Biol Chem, 280 (45): 37763-71. [PMID:16150690]
8. Voets T, Nilius B, Hoefs S, van der Kemp AW, Droogmans G, Bindels RJ, Hoenderop JG. (2004) TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem, 279 (1): 19-25. [PMID:14576148]
9. Walder RY, Landau D, Meyer P, Shalev H, Tsolia M, Borochowitz Z, Boettger MB, Beck GE, Englehardt RK, Carmi R et al.. (2002) Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet, 31 (2): 171-4. [PMID:12032570]
10. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]
11. Woudenberg-Vrenken TE, Sukinta A, van der Kemp AW, Bindels RJ, Hoenderop JG. (2011) Transient receptor potential melastatin 6 knockout mice are lethal whereas heterozygous deletion results in mild hypomagnesemia. Nephron Physiol, 117 (2): p11-9. [PMID:20814221]