Q8R4D5 · TRPM8_MOUSE
- ProteinTransient receptor potential cation channel subfamily M member 8
- GeneTrpm8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1104 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Non-selective ion channel permeable to monovalent and divalent cations, including Na+, K+, and Ca2+, with higher permeability for Ca2+ (PubMed:11893340, PubMed:12654248, PubMed:15190109).
Activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality (PubMed:12654248, PubMed:15190109, PubMed:25998021).
Activated by cool temperatures (<23-28 degrees Celsius) and by chemical ligands evoking a sensation of coolness, such as menthol and icilin, therefore plays a central role in the detection of environmental cold temperatures (PubMed:12654248, PubMed:15190109, PubMed:17481391).
TRPM8 is a voltage-dependent channel; its activation by cold or chemical ligands shifts its voltage thresholds towards physiological membrane potentials, leading to the opening of the channel (By similarity).
In addition to its critical role in temperature sensing, regulates basal tear secretion by sensing evaporation-induced cooling and changes in osmolality (PubMed:25998021).
Activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality (PubMed:12654248, PubMed:15190109, PubMed:25998021).
Activated by cool temperatures (<23-28 degrees Celsius) and by chemical ligands evoking a sensation of coolness, such as menthol and icilin, therefore plays a central role in the detection of environmental cold temperatures (PubMed:12654248, PubMed:15190109, PubMed:17481391).
TRPM8 is a voltage-dependent channel; its activation by cold or chemical ligands shifts its voltage thresholds towards physiological membrane potentials, leading to the opening of the channel (By similarity).
In addition to its critical role in temperature sensing, regulates basal tear secretion by sensing evaporation-induced cooling and changes in osmolality (PubMed:25998021).
Catalytic activity
- Ca2+(in) = Ca2+(out)
- Na+(in) = Na+(out)
- K+(in) = K+(out)
Activity regulation
Activated by cold temperatures and by both natural and synthetic cooling compounds such as menthol and icilin (PubMed:11893340, PubMed:12654248, PubMed:15190109, PubMed:17481391).
Activation of the channel requires the presence of PI(4,5)P2; PI(4,5)P2 is necessary to gate the channel (By similarity).
Activated by intracellular Ca2+ (By similarity).
Activation of the channel requires the presence of PI(4,5)P2; PI(4,5)P2 is necessary to gate the channel (By similarity).
Activated by intracellular Ca2+ (By similarity).
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | external side of plasma membrane | |
Cellular Component | membrane | |
Cellular Component | membrane raft | |
Cellular Component | plasma membrane | |
Cellular Component | plasma membrane raft | |
Molecular Function | calcium channel activity | |
Molecular Function | identical protein binding | |
Molecular Function | monoatomic ion channel activity | |
Biological Process | calcium ion transport | |
Biological Process | intracellular calcium ion homeostasis | |
Biological Process | positive regulation of cold-induced thermogenesis | |
Biological Process | response to cold | |
Biological Process | response to temperature stimulus | |
Biological Process | thermoception |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTransient receptor potential cation channel subfamily M member 8
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8R4D5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Lipid raft association modulates TRPM8 channel activity.
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-733 | Cytoplasmic | ||||
Sequence: MSFEGARLSMRSRRNGTMGSTRTLYSSVSRSTDVSYSDSDLVNFIQANFKKRECVFFTRDSKAMENICKCGYAQSQHIEGTQINQNEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYLRLSCDTDSETLYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWILTGGTHYGLMKYIGEVVRDNTISRNSEENIVAIGIAAWGMVSNRDTLIRSCDDEGHFSAQYIMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTSQDSNYGGKIPIVCFAQGGGRETLKAINTSVKSKIPCVVVEGSGQIADVIASLVEVEDVLTSSMVKEKLVRFLPRTVSRLPEEEIESWIKWLKEILESSHLLTVIKMEEAGDEIVSNAISYALYKAFSTNEQDKDNWNGQLKLLLEWNQLDLASDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLENGLNLQKFLTNEVLTELFSTHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRSFWKEDRSSREDLDVELHDASLTTRHPLQALFIWAILQNKKELSKVIWEQTKGCTLAALGASKLLKTLAKVKNDINAAGESEELANEYETRAVELFTECYSNDEDLAEQLLVYSCEAWGGSNCLELAVEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGLVSFRKKPIDKHKKLLWYYVAFFTS | ||||||
Transmembrane | 734-758 | Helical; Name=1 | ||||
Sequence: PFVVFSWNVVFYIAFLLLFAYVLLM | ||||||
Topological domain | 759-765 | Extracellular | ||||
Sequence: DFHSVPH | ||||||
Transmembrane | 766-789 | Helical; Name=2 | ||||
Sequence: TPELILYALVFVLFCDEVRQWYMN | ||||||
Topological domain | 790-796 | Cytoplasmic | ||||
Sequence: GVNYFTD | ||||||
Transmembrane | 797-817 | Helical; Name=3 | ||||
Sequence: LWNVMDTLGLFYFIAGIVFRL | ||||||
Topological domain | 818-822 | Extracellular | ||||
Sequence: HSSNK | ||||||
Transmembrane | 823-848 | Helical; Name=4 | ||||
Sequence: SSLYSGRVIFCLDYIIFTLRLIHIFT | ||||||
Topological domain | 849-853 | Cytoplasmic | ||||
Sequence: VSRNL | ||||||
Transmembrane | 854-890 | Helical; Name=5 | ||||
Sequence: GPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILR | ||||||
Topological domain | 891-895 | Extracellular | ||||
Sequence: QNEQR | ||||||
Intramembrane | 896-912 | Pore-forming | ||||
Sequence: WRWIFRSVIYEPYLAMF | ||||||
Topological domain | 913-953 | Extracellular | ||||
Sequence: GQVPSDVDSTTYDFSHCTFSGNESKPLCVELDEHNLPRFPE | ||||||
Transmembrane | 954-984 | Helical; Name=6 | ||||
Sequence: WITIPLVCIYMLSTNILLVNLLVAMFGYTVG | ||||||
Topological domain | 985-1104 | Cytoplasmic | ||||
Sequence: IVQENNDQVWKFQRYFLVQEYCNRLNIPFPFVVFAYFYMVVKKCFKCCCKEKNMESNACCFRNEDNETLAWEGVMKENYLVKINTKANDNSEEMRHRFRQLDSKLNDLKSLLKEIANNIK |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Trpm8-deficient mice have severe behavioral deficits in response to cold stimuli.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 821 | No effect on glycosylation or ability to form functional channels. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 929 | Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. | ||||
Sequence: C → A | ||||||
Mutagenesis | 934 | Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli. | ||||
Sequence: N → D | ||||||
Mutagenesis | 934 | Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli. | ||||
Sequence: N → K | ||||||
Mutagenesis | 934 | Abolishes glycosylation. Shifts threshold of temperature activation from 26.5 to 24 degrees Celsius. Reduced cell surface expression, association with lipid rafts and response to cold. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 940 | Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. | ||||
Sequence: C → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 65 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000215334 | 1-1104 | Transient receptor potential cation channel subfamily M member 8 | |||
Sequence: MSFEGARLSMRSRRNGTMGSTRTLYSSVSRSTDVSYSDSDLVNFIQANFKKRECVFFTRDSKAMENICKCGYAQSQHIEGTQINQNEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYLRLSCDTDSETLYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWILTGGTHYGLMKYIGEVVRDNTISRNSEENIVAIGIAAWGMVSNRDTLIRSCDDEGHFSAQYIMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTSQDSNYGGKIPIVCFAQGGGRETLKAINTSVKSKIPCVVVEGSGQIADVIASLVEVEDVLTSSMVKEKLVRFLPRTVSRLPEEEIESWIKWLKEILESSHLLTVIKMEEAGDEIVSNAISYALYKAFSTNEQDKDNWNGQLKLLLEWNQLDLASDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLENGLNLQKFLTNEVLTELFSTHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRSFWKEDRSSREDLDVELHDASLTTRHPLQALFIWAILQNKKELSKVIWEQTKGCTLAALGASKLLKTLAKVKNDINAAGESEELANEYETRAVELFTECYSNDEDLAEQLLVYSCEAWGGSNCLELAVEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGLVSFRKKPIDKHKKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHTPELILYALVFVLFCDEVRQWYMNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFTLRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIFRSVIYEPYLAMFGQVPSDVDSTTYDFSHCTFSGNESKPLCVELDEHNLPRFPEWITIPLVCIYMLSTNILLVNLLVAMFGYTVGIVQENNDQVWKFQRYFLVQEYCNRLNIPFPFVVFAYFYMVVKKCFKCCCKEKNMESNACCFRNEDNETLAWEGVMKENYLVKINTKANDNSEEMRHRFRQLDSKLNDLKSLLKEIANNIK | ||||||
Glycosylation | 934 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylation is not essential for but facilitates cell surface expression, multimerization, association with lipid rafts and ion channel activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in dorsal root and trigeminal ganglia. Specifically expressed in a subset of pain- and temperature-sensing neurons. Not expressed in heavily myelinated neurons. Not expressed in neurons expressing TRPA1 or TRPV1.
Gene expression databases
Interaction
Subunit
Homotetramer (PubMed:17015441, PubMed:35662242, PubMed:36227998).
Interacts (via N-terminus and C-terminus domains) with TCAF1; the interaction stimulates TRPM8 channel activity. Interacts (via N-terminus and C-terminus domains) with TCAF2; the interaction inhibits TRPM8 channel activity (By similarity).
Interacts (via N-terminus and C-terminus domains) with TCAF1; the interaction stimulates TRPM8 channel activity. Interacts (via N-terminus and C-terminus domains) with TCAF2; the interaction inhibits TRPM8 channel activity (By similarity).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-22 | Disordered | ||||
Sequence: MSFEGARLSMRSRRNGTMGSTR | ||||||
Coiled coil | 1069-1104 | |||||
Sequence: TKANDNSEEMRHRFRQLDSKLNDLKSLLKEIANNIK |
Domain
Cooling agents bind within a pocket formed entirely by the S1-S4 helices that opens to the cytoplasm.
The coiled coil region is required for multimerization.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,104
- Mass (Da)127,710
- Last updated2013-02-06 v3
- Checksum16B5D6FBED2BE96D
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF481480 EMBL· GenBank· DDBJ | AAL79553.1 EMBL· GenBank· DDBJ | mRNA | ||
AY095352 EMBL· GenBank· DDBJ | AAM23261.1 EMBL· GenBank· DDBJ | mRNA | ||
AC087780 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC102505 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH466520 EMBL· GenBank· DDBJ | EDL40112.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC117934 EMBL· GenBank· DDBJ | AAI17935.1 EMBL· GenBank· DDBJ | mRNA |