Q8R4D5 · TRPM8_MOUSE

  • Protein
    Transient receptor potential cation channel subfamily M member 8
  • Gene
    Trpm8
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

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).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site782Ca2+ (UniProtKB | ChEBI)
Binding site785Ca2+ (UniProtKB | ChEBI)
Binding site799Ca2+ (UniProtKB | ChEBI)
Binding site802Ca2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentexternal side of plasma membrane
Cellular Componentmembrane
Cellular Componentmembrane raft
Cellular Componentplasma membrane
Cellular Componentplasma membrane raft
Molecular Functioncalcium channel activity
Molecular Functionidentical protein binding
Molecular Functionmonoatomic ion channel activity
Biological Processcalcium ion transport
Biological Processintracellular calcium ion homeostasis
Biological Processpositive regulation of cold-induced thermogenesis
Biological Processresponse to cold
Biological Processresponse to temperature stimulus
Biological Processthermoception

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Transient receptor potential cation channel subfamily M member 8
  • Alternative names
    • Long transient receptor potential channel 6 (LTrpC-6; LTrpC6)
    • Transient receptor potential p8 (Trp-p8)

Gene names

    • Name
      Trpm8
    • Synonyms
      Ltrpc6, Trpp8

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • OF1
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8R4D5
  • Secondary accessions
    • E9Q165
    • Q148W9

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Membrane raft
Note: Lipid raft association modulates TRPM8 channel activity.

Features

Showing features for topological domain, transmembrane, intramembrane.

TypeIDPosition(s)Description
Topological domain1-733Cytoplasmic
Transmembrane734-758Helical; Name=1
Topological domain759-765Extracellular
Transmembrane766-789Helical; Name=2
Topological domain790-796Cytoplasmic
Transmembrane797-817Helical; Name=3
Topological domain818-822Extracellular
Transmembrane823-848Helical; Name=4
Topological domain849-853Cytoplasmic
Transmembrane854-890Helical; Name=5
Topological domain891-895Extracellular
Intramembrane896-912Pore-forming
Topological domain913-953Extracellular
Transmembrane954-984Helical; Name=6
Topological domain985-1104Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Trpm8-deficient mice have severe behavioral deficits in response to cold stimuli.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis821No effect on glycosylation or ability to form functional channels.
Mutagenesis929Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation.
Mutagenesis934Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli.
Mutagenesis934Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli.
Mutagenesis934Abolishes 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.
Mutagenesis940Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation.

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.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002153341-1104Transient receptor potential cation channel subfamily M member 8
Glycosylation934N-linked (GlcNAc...) (complex) asparagine

Post-translational modification

N-glycosylation is not essential for but facilitates cell surface expression, multimerization, association with lipid rafts and ion channel activity.

Keywords

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).

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, coiled coil.

TypeIDPosition(s)Description
Region1-22Disordered
Coiled coil1069-1104

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,104
  • Mass (Da)
    127,710
  • Last updated
    2013-02-06 v3
  • Checksum
    16B5D6FBED2BE96D
MSFEGARLSMRSRRNGTMGSTRTLYSSVSRSTDVSYSDSDLVNFIQANFKKRECVFFTRDSKAMENICKCGYAQSQHIEGTQINQNEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYLRLSCDTDSETLYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWILTGGTHYGLMKYIGEVVRDNTISRNSEENIVAIGIAAWGMVSNRDTLIRSCDDEGHFSAQYIMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTSQDSNYGGKIPIVCFAQGGGRETLKAINTSVKSKIPCVVVEGSGQIADVIASLVEVEDVLTSSMVKEKLVRFLPRTVSRLPEEEIESWIKWLKEILESSHLLTVIKMEEAGDEIVSNAISYALYKAFSTNEQDKDNWNGQLKLLLEWNQLDLASDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLENGLNLQKFLTNEVLTELFSTHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRSFWKEDRSSREDLDVELHDASLTTRHPLQALFIWAILQNKKELSKVIWEQTKGCTLAALGASKLLKTLAKVKNDINAAGESEELANEYETRAVELFTECYSNDEDLAEQLLVYSCEAWGGSNCLELAVEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGLVSFRKKPIDKHKKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHTPELILYALVFVLFCDEVRQWYMNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFTLRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIFRSVIYEPYLAMFGQVPSDVDSTTYDFSHCTFSGNESKPLCVELDEHNLPRFPEWITIPLVCIYMLSTNILLVNLLVAMFGYTVGIVQENNDQVWKFQRYFLVQEYCNRLNIPFPFVVFAYFYMVVKKCFKCCCKEKNMESNACCFRNEDNETLAWEGVMKENYLVKINTKANDNSEEMRHRFRQLDSKLNDLKSLLKEIANNIK

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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