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TRPM5

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 497

Nomenclature: TRPM5

Family: Transient Receptor Potential channels (TRP)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1165 11p15.5 TRPM5 transient receptor potential cation channel subfamily M member 5 22
Mouse 6 1 1158 7 F5 Trpm5 transient receptor potential cation channel, subfamily M, member 5 5
Rat 6 1 1158 1q42 Trpm5 transient receptor potential cation channel, subfamily M, member 5
Previous and Unofficial Names Click here for help
MTR1 | TRP-T | L-TRPC5 | transient receptor potential cation channel
Database Links Click here for help
Alphafold Q9NZQ8 (Hs), Q9JJH7 (Mm)
CATH/Gene3D 1.25.40.20
ChEMBL Target CHEMBL1628468 (Hs), CHEMBL3886124 (Mm)
Ensembl Gene ENSG00000070985 (Hs), ENSMUSG00000009246 (Mm), ENSRNOG00000020484 (Rn)
Entrez Gene 29850 (Hs), 56843 (Mm), 365391 (Rn)
Human Protein Atlas ENSG00000070985 (Hs)
KEGG Gene hsa:29850 (Hs), mmu:56843 (Mm), rno:365391 (Rn)
OMIM 604600 (Hs)
Pharos Q9NZQ8 (Hs)
RefSeq Nucleotide NM_014555 (Hs), NM_020277 (Mm), NM_001191896 (Rn)
RefSeq Protein NP_055370 (Hs), NP_064673 (Mm), NP_001178825 (Rn)
UniProtKB Q9NZQ8 (Hs), Q9JJH7 (Mm)
Wikipedia TRPM5 (Hs)
Functional Characteristics Click here for help
γ = 15-25 pS; conducts monovalent cations selectively (PCa/PNa = 0.05); strong outward rectification; slow activation at positive potentials, rapid inactivation at negative potentials; activated and subsequently desensitized by [Ca2+]I
Ion Selectivity and Conductance Comments
Nonselective for monovalent cations, impermeable to divalent cations. Average single-channel conductance of mTRPM5 is 20-25 pS [8,23]. Instantaneous single-channel conductance is linear [23].
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  100.0 18.8 29 HEK 293 cells. Mouse
Inactivation  - -
Deactivation  - 9.1 – 50.2 8,29
Comments  Heat activation of TRPM5 is the result of a drastic leftward shift of the voltage dependence of activation (-7.0 mV.°C-1) [26].
Physical activators (Human)
membrane depolarization (V½ = 0 to + 120 mV dependent upon conditions), heat (Q10 = 10.3 @ -75 mV between 15 and 25°C)

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
compound 39 [PMID: 36402081] Small molecule or natural product Hs Agonist 7.5 pEC50 - - 25
⤷ pEC50 7.5 [25]
Description: Detection method FLIPR FMP dye assay.
intracellular Ca2+ Click here for species-specific activity table Ligand is endogenous in the given species Mm Agonist 4.5 – 6.2 pEC50 - -80.0 – 80.0 8,14,29
⤷ pEC50 4.5 – 6.2 (EC50 3x10-5 – 7x10-7 M) [8,14,29]
Holding voltage: -80.0 – 80.0 mV
View species-specific activator tables
Activator Comments
Desensitisation of TRPM5 is modulated by PIP2, which acts as a co-factor for activation [14]. Human TRPM5 expressed in HEK293 cells is sensitive to rapid but not slow elevations in Ca2+ [23]. Arachidonic acid (10µM) activates mouse Trpm5 in transfected HEK293 cells [20]. Flash photolysis of caged IP3 activates mTrpm5 current in whole-cell but not excised patches [32].

In a calcium uncaging experiment mouse Trpm5 is activated with a time constant (τ) of 1.9ms at 100mV [29].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
flufenamic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - 4.6 pIC50 - -
⤷ pIC50 4.6 (IC50 2.4x10-5 M)
intracellular spermine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - 4.4 pIC50 - -
⤷ pIC50 4.4 (IC50 3.7x10-5 M)
Extracellular H+ Click here for species-specific activity table Hs - 3.2 pIC50 - -
⤷ pIC50 3.2 (IC50 6.3x10-4 M)
Channel Blocker Comments
TRPM5 is sensitive to pH below 7.0, with complete block at around pH 5.9 [15]. Histidines in the pore region (His-934) and a glutamate in the S3-S4 extracellular linker (Glu-830) enhance sensitivity to proton block [15].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
APV207095A Small molecule or natural product Hs Potentiation 5.0 pEC50 30
⤷ pEC50 5.0 (EC50 9.4x10-6 M) [30]
Description: Determined via whole cell patch clamp experiments, with free [Ca2+]i at 1 μM
APV207094A Small molecule or natural product Hs Potentiation 4.4 pEC50 30
⤷ pEC50 4.4 (EC50 3.71x10-5 M) [30]
Description: Determined via whole cell patch clamp experiments, with free [Ca2+]i at 1 μM
APV207010A Small molecule or natural product Hs Potentiation 4.4 pEC50 30
⤷ pEC50 4.4 (EC50 3.84x10-5 M) [30]
Description: Determined via whole cell patch clamp experiments, with free [Ca2+]i at 1 μM
APV206690A Small molecule or natural product Hs Potentiation 4.0 pEC50 30
⤷ pEC50 4.0 (EC50 9.22x10-5 M) [30]
Description: Determined via whole cell patch clamp experiments, with free [Ca2+]i at 1 μM
Immunopharmacology Comments
Expressed on mouse B cells [21].
Tissue Distribution Click here for help
Intestines, pancreas, prostate, kidney, pituitary
Species:  Human
Technique:  RT-PCR
References:  1,6,17
Taste tissue, olfactory epithelium, pancreatic β-cells, stomach, intestines, uterus, testes, cerebellar Purkinje cells, vasopressin-secreting hypothalamic neurons.
Species:  Mouse
Technique:  Immunocytochemistry, northern blot, in situ hybridisation.
References:  3,7,10-12,24,31
Vasopressin-secreting hypothalamic neurons
Species:  Rat
Technique:  Immunocytochemistry, RT-PCR
References:  27
Functional Assays Click here for help
Patch clamp (whole-cell and single-channel recordings).
Species:  Mouse
Tissue:  HEK 293 or CHO cells transfected with TRPM5 vector.
Response measured:  Ca2+ evoked currents.
References:  8,14,18-19,23-24,26,29,31
Two-electrode voltage clamp technique.
Species:  Mouse
Tissue:  Xenopus laevis oocytes injected with TRPM5 cDNA.
Response measured:  Ca2+ evoked currents.
References:  24
Ca2+ imaging
Species:  Mouse
Tissue:  Taste cells
Response measured:  Ca2+ elevation in response to chemical activators or membrane depolarization
References:  9
Patch clamp (whole-cell recordings), Ca2+ uncaging, Ca2+ imaging, glucose-induced insulin secretion
Species:  Mouse
Tissue:  Pancreatic islet cells
Response measured:  Ca2+ evoked currents, glucose-stimulated Ca2+ oscillations and insulin secretion
References:  3
Field-potential recording, Ca2+ imaging
Species:  Mouse
Tissue:  Olfactory epithelium
Response measured:  Odorant-induced field potentials, odorant-induced Ca2+ elevations
References:  13
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Mouse
Tissue:  Taste cells
Response measured:  Linoleic-acid evoked currents and Ca2+ elevations
References:  16
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Mouse
Tissue:  Cerebellar slice
Response measured:  Depolarization-induced slow current and Ca2+ elevations
References:  10
Patch clamp (whole-cell recordings)
Species:  Human
Tissue:  HEK293 cells expressing TRPM5
Response measured:  Ca2+ and temperature evoked currents
References:  26
Patch clamp (whole-cell and single-channel recordings)
Species:  Human
Tissue:  Transfected HEK293 cells (human), taste cells from knockout mice
Response measured:  Ca2+ and IP3 evoked currents
References:  26
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Human
Tissue:  Human colon adenocarcinoma goblet cells (HT29-18N2, serum starved)
Response measured:  Ca2+-induced currents and Ca2+ elevations
References:  17
Physiological Functions Click here for help
Bitter, sweet, umami receptor channel. Free fatty acid receptor channel.
Species:  Mouse
Tissue:  Taste tissue.
References:  4,16,24,26,31
Mucin 5AC (MUC5AC) secretion
Species:  Human
Tissue:  Colonic goblet cells
References:  17
Insulin secretion
Species:  Mouse
Tissue:  Pancreatic islets
References:  2-3
Irritant odor receptor channel
Species:  Mouse
Tissue:  Olfactory epithelium
References:  12-13,28
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1861718  MP:0004210 abnormal bitter taste sensitivity PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6		 MGI:1861718  MP:0004210 abnormal bitter taste sensitivity PMID: 16355226 
Trpm4tm1.1Knt|Trpm5tm1Csz Trpm4tm1.1Knt/Trpm4tm1.1Knt,Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ		 MGI:1861718  MGI:1915917  MP:0002376 abnormal dendritic cell physiology PMID: 18758465 
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1861718  MP:0001985 abnormal gustatory system physiology PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6		 MGI:1861718  MP:0004212 abnormal salty taste sensitivity PMID: 16355226 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6		 MGI:1861718  MP:0004211 abnormal sour taste sensitivity PMID: 16355226 
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1861718  MP:0004209 abnormal sweet taste sensitivity PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6		 MGI:1861718  MP:0004209 abnormal sweet taste sensitivity PMID: 16355226 
Trpm5tm1Csz Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1861718  MP:0001986 abnormal taste sensitivity PMID: 12581520 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6		 MGI:1861718  MP:0001986 abnormal taste sensitivity PMID: 16355226 
Trpm5tm1Dgen Trpm5tm1Dgen/Trpm5tm1Dgen
B6.129P2-Trpm5		 MGI:1861718  MP:0001986 abnormal taste sensitivity PMID: 19244541 
Trpm5tm1Sdmk Trpm5tm1Sdmk/Trpm5tm1Sdmk
involves: C57BL/6		 MGI:1861718  MP:0004213 abnormal unami taste sensitivity PMID: 15738181  16355226 
Trpm4tm1.1Knt|Trpm5tm1Csz Trpm4tm1.1Knt/Trpm4tm1.1Knt,Trpm5tm1Csz/Trpm5tm1Csz
involves: 129S1/Sv * 129X1/SvJ		 MGI:1861718  MGI:1915917  MP:0008127 decreased dendritic cell number PMID: 18758465 
Trpm5tm1Dgen Trpm5tm1Dgen/Trpm5tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1861718  MP:0002169 no abnormal phenotype detected

References

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1. Bezençon C, le Coutre J, Damak S. (2007) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses, 32 (1): 41-9. [PMID:17030556]

2. Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D. (2010) TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Arch, 460 (1): 69-76. [PMID:20393858]

3. Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, Owsianik G, Talavera K, Voets T, Margolskee RF et al.. (2010) Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice. Proc Natl Acad Sci USA, 107 (11): 5208-13. [PMID:20194741]

4. Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Pérez CA, Shigemura N, Yoshida R, Mosinger Jr B, Glendinning JI, Ninomiya Y et al.. (2006) Trpm5 null mice respond to bitter, sweet, and umami compounds. Chem Senses, 31 (3): 253-64. [PMID:16436689]

5. Enklaar T, Esswein M, Oswald M, Hilbert K, Winterpacht A, Higgins M, Zabel B, Prawitt D. (2000) Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family. Genomics, 67 (2): 179-87. [PMID:10903843]

6. Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S. (2006) Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res, 26 (3): 159-78. [PMID:16777713]

7. Hansen A, Finger TE. (2008) Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice. BMC Neurosci, 9: 115. [PMID:19055837]

8. Hofmann T, Chubanov V, Gudermann T, Montell C. (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol, 13 (13): 1153-8. [PMID:12842017]

9. Huang YA, Roper SD. (2010) Intracellular Ca(2+) and TRPM5-mediated membrane depolarization produce ATP secretion from taste receptor cells. J Physiol (Lond.), 588 (Pt 13): 2343-50. [PMID:20498227]

10. Kim YS, Kang E, Makino Y, Park S, Shin JH, Song H, Launay P, Linden DJ. (2013) Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells. J Neurophysiol, 109 (4): 1174-81. [PMID:23197456]

11. Lin W, Ezekwe Jr EA, Zhao Z, Liman ER, Restrepo D. (2008) TRPM5-expressing microvillous cells in the main olfactory epithelium. BMC Neurosci, 9: 114. [PMID:19025635]

12. Lin W, Margolskee R, Donnert G, Hell SW, Restrepo D. (2007) Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proc Natl Acad Sci USA, 104 (7): 2471-6. [PMID:17267604]

13. Lin W, Ogura T, Margolskee RF, Finger TE, Restrepo D. (2008) TRPM5-expressing solitary chemosensory cells respond to odorous irritants. J Neurophysiol, 99 (3): 1451-60. [PMID:18160424]

14. Liu D, Liman ER. (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci USA, 100 (25): 15160-5. [PMID:14657398]

15. Liu D, Zhang Z, Liman ER. (2005) Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains. J Biol Chem, 280 (21): 20691-9. [PMID:15731110]

16. Liu P, Shah BP, Croasdell S, Gilbertson TA. (2011) Transient receptor potential channel type M5 is essential for fat taste. J Neurosci, 31 (23): 8634-42. [PMID:21653867]

17. Mitrovic S, Nogueira C, Cantero-Recasens G, Kiefer K, Fernández-Fernández JM, Popoff JF, Casano L, Bard FA, Gomez R, Valverde MA et al.. (2013) TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells. Elife, 2: e00658. [PMID:23741618]

18. Nilius B, Prenen J, Janssens A, Owsianik G, Wang C, Zhu MX, Voets T. (2005) The selectivity filter of the cation channel TRPM4. J Biol Chem, 280 (24): 22899-906. [PMID:15845551]

19. Nilius B, Prenen J, Janssens A, Voets T, Droogmans G. (2004) Decavanadate modulates gating of TRPM4 cation channels. J Physiol (Lond.), 560 (Pt 3): 753-65. [PMID:15331675]

20. Oike H, Wakamori M, Mori Y, Nakanishi H, Taguchi R, Misaka T, Matsumoto I, Abe K. (2006) Arachidonic acid can function as a signaling modulator by activating the TRPM5 cation channel in taste receptor cells. Biochim Biophys Acta, 1761 (9): 1078-84. [PMID:16935556]

21. 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]

22. Prawitt D, Enklaar T, Klemm G, Gärtner B, Spangenberg C, Winterpacht A, Higgins M, Pelletier J, Zabel B. (2000) Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression. Hum Mol Genet, 9 (2): 203-16. [PMID:10607831]

23. Prawitt D, Monteilh-Zoller MK, Brixel L, Spangenberg C, Zabel B, Fleig A, Penner R. (2003) TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc Natl Acad Sci USA, 100 (25): 15166-71. [PMID:14634208]

24. Pérez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF. (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci, 5 (11): 1169-76. [PMID:12368808]

25. Sabat M, Raveglia LF, Aldegheri L, Barilli A, Bianchi F, Brault L, Brodbeck D, Feriani A, Lingard I, Miura J et al.. (2022) The discovery of (1R, 3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile, a potent and selective agonist of human transient receptor potential cation channel subfamily m member 5 (TRPM5) and evaluation of as a potential gastrointestinal prokinetic agent. Bioorg Med Chem, 76: 117084. [PMID:36402081]

26. Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B. (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature, 438 (7070): 1022-5. [PMID:16355226]

27. Teruyama R, Sakuraba M, Kurotaki H, Armstrong WE. (2011) Transient receptor potential channel m4 and m5 in magnocellular cells in rat supraoptic and paraventricular nuclei. J Neuroendocrinol, 23 (12): 1204-13. [PMID:21848647]

28. Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE. (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci USA, 107 (7): 3210-5. [PMID:20133764]

29. Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, Nilius B. (2005) Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell Calcium, 37 (3): 267-78. [PMID:15670874]

30. Virginio C, Aldegheri L, Nola S, Brodbeck D, Brault L, Raveglia LF, Barilli A, Sabat M, Myers R. (2022) Identification of positive modulators of TRPM5 channel from a high-throughput screen using a fluorescent membrane potential assay. SLAS Discov, 27 (1): 55-64. [PMID:35058176]

31. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ. (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell, 112 (3): 293-301. [PMID:12581520]

32. Zhang Z, Zhao Z, Margolskee R, Liman E. (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci, 27 (21): 5777-86. [PMID:17522321]

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