UniProtKB - Q8R4D5 (TRPM8_MOUSE)
Protein
Transient receptor potential cation channel subfamily M member 8
Gene
Trpm8
Organism
Mus musculus (Mouse)
Status
Functioni
Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonists menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing.2 Publications
GO - Molecular functioni
- calcium channel activity Source: MGI
- ion channel activity Source: MGI
- protein homodimerization activity Source: MGI
GO - Biological processi
- calcium ion transport Source: MGI
- cellular calcium ion homeostasis Source: MGI
- detection of temperature stimulus Source: InterPro
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- protein homotetramerization Source: MGI
- protein homotrimerization Source: MGI
- response to cold Source: MGI
- response to temperature stimulus Source: MGI
- thermoception Source: MGI
Keywordsi
Molecular function | Ion channel |
Biological process | Ion transport, Sensory transduction, Transport |
Enzyme and pathway databases
Reactomei | R-MMU-3295583 TRP channels |
Names & Taxonomyi
Protein namesi | Recommended name: Transient receptor potential cation channel subfamily M member 8Alternative name(s): Long transient receptor potential channel 6 Short name: LTrpC-6 Short name: LTrpC6 Transient receptor potential p8 Short name: Trp-p8 |
Gene namesi | Name:Trpm8 Synonyms:Ltrpc6, Trpp8 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2181435 Trpm8 |
Subcellular locationi
Plasma membrane
Other locations
Note: Localizes to membrane rafts but is also located in the cell membrane outside of these regions where channel response to cold is enhanced compared to membrane rafts.
Plasma Membrane
- external side of plasma membrane Source: MGI
- plasma membrane Source: MGI
Other locations
- integral component of membrane Source: MGI
- membrane Source: MGI
- membrane raft Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 691 | CytoplasmicSequence analysisAdd BLAST | 691 | |
Transmembranei | 692 – 712 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 713 – 734 | ExtracellularSequence analysisAdd BLAST | 22 | |
Transmembranei | 735 – 755 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 756 – 759 | CytoplasmicSequence analysis | 4 | |
Transmembranei | 760 – 780 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 781 – 794 | ExtracellularSequence analysisAdd BLAST | 14 | |
Transmembranei | 795 – 815 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 816 – 829 | CytoplasmicSequence analysisAdd BLAST | 14 | |
Transmembranei | 830 – 850 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 851 – 958 | ExtracellularSequence analysisAdd BLAST | 108 | |
Transmembranei | 959 – 979 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 980 – 1104 | CytoplasmicSequence analysisAdd BLAST | 125 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 821 | N → Q: No effect on glycosylation or ability to form functional channels. 1 Publication | 1 | |
Mutagenesisi | 929 | C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication | 1 | |
Mutagenesisi | 934 | N → D: Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli. 3 Publications | 1 | |
Mutagenesisi | 934 | N → K: Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli. 3 Publications | 1 | |
Mutagenesisi | 934 | N → Q: 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. 3 Publications | 1 | |
Mutagenesisi | 940 | C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3108632 |
GuidetoPHARMACOLOGYi | 500 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000215334 | 1 – 1104 | Transient receptor potential cation channel subfamily M member 8Add BLAST | 1104 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 934 | N-linked (GlcNAc...) (complex) asparagine2 Publications | 1 |
Post-translational modificationi
N-glycosylation is not essential for but facilitates cell surface expression, multimerization, association with lipid rafts and ion channel activity.2 Publications
Keywords - PTMi
GlycoproteinProteomic databases
PaxDbi | Q8R4D5 |
PRIDEi | Q8R4D5 |
PTM databases
iPTMneti | Q8R4D5 |
PhosphoSitePlusi | Q8R4D5 |
SwissPalmi | Q8R4D5 |
Expressioni
Tissue specificityi
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 TRPV1.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000036251 Expressed in 19 organ(s), highest expression level in dorsal root ganglion |
Genevisiblei | Q8R4D5 MM |
Interactioni
Subunit structurei
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). Homotetramer.By similarity1 Publication
GO - Molecular functioni
- protein homodimerization activity Source: MGI
Protein-protein interaction databases
BioGridi | 228590, 1 interactor |
DIPi | DIP-61852N |
IntActi | Q8R4D5, 1 interactor |
STRINGi | 10090.ENSMUSP00000036991 |
Chemistry databases
BindingDBi | Q8R4D5 |
Structurei
3D structure databases
ProteinModelPortali | Q8R4D5 |
SMRi | Q8R4D5 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 1069 – 1104 | Sequence analysisAdd BLAST | 36 |
Domaini
The coiled coil region is required for multimerization.By similarity
Sequence similaritiesi
Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM8 sub-subfamily. [View classification]Curated
Keywords - Domaini
Coiled coil, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG410KCTC Eukaryota ENOG4110YBY LUCA |
GeneTreei | ENSGT00940000160270 |
HOGENOMi | HOG000236350 |
HOVERGENi | HBG100888 |
InParanoidi | Q8R4D5 |
KOi | K04983 |
OMAi | YIMDDFT |
OrthoDBi | 738147at2759 |
PhylomeDBi | Q8R4D5 |
TreeFami | TF314204 |
Family and domain databases
InterProi | View protein in InterPro IPR029603 TRPM8 |
PANTHERi | PTHR13800:SF9 PTHR13800:SF9, 1 hit |
i Sequence
Sequence statusi: Complete.
Q8R4D5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSFEGARLSM RSRRNGTMGS TRTLYSSVSR STDVSYSDSD LVNFIQANFK
60 70 80 90 100
KRECVFFTRD SKAMENICKC GYAQSQHIEG TQINQNEKWN YKKHTKEFPT
110 120 130 140 150
DAFGDIQFET LGKKGKYLRL SCDTDSETLY ELLTQHWHLK TPNLVISVTG
160 170 180 190 200
GAKNFALKPR MRKIFSRLIY IAQSKGAWIL TGGTHYGLMK YIGEVVRDNT
210 220 230 240 250
ISRNSEENIV AIGIAAWGMV SNRDTLIRSC DDEGHFSAQY IMDDFTRDPL
260 270 280 290 300
YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTS QDSNYGGKIP
310 320 330 340 350
IVCFAQGGGR ETLKAINTSV KSKIPCVVVE GSGQIADVIA SLVEVEDVLT
360 370 380 390 400
SSMVKEKLVR FLPRTVSRLP EEEIESWIKW LKEILESSHL LTVIKMEEAG
410 420 430 440 450
DEIVSNAISY ALYKAFSTNE QDKDNWNGQL KLLLEWNQLD LASDEIFTND
460 470 480 490 500
RRWESADLQE VMFTALIKDR PKFVRLFLEN GLNLQKFLTN EVLTELFSTH
510 520 530 540 550
FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRSFWKEDR SSREDLDVEL
560 570 580 590 600
HDASLTTRHP LQALFIWAIL QNKKELSKVI WEQTKGCTLA ALGASKLLKT
610 620 630 640 650
LAKVKNDINA AGESEELANE YETRAVELFT ECYSNDEDLA EQLLVYSCEA
660 670 680 690 700
WGGSNCLELA VEATDQHFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF
710 720 730 740 750
IIPLVGCGLV SFRKKPIDKH KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL
760 770 780 790 800
LFAYVLLMDF HSVPHTPELI LYALVFVLFC DEVRQWYMNG VNYFTDLWNV
810 820 830 840 850
MDTLGLFYFI AGIVFRLHSS NKSSLYSGRV IFCLDYIIFT LRLIHIFTVS
860 870 880 890 900
RNLGPKIIML QRMLIDVFFF LFLFAVWMVA FGVARQGILR QNEQRWRWIF
910 920 930 940 950
RSVIYEPYLA MFGQVPSDVD STTYDFSHCT FSGNESKPLC VELDEHNLPR
960 970 980 990 1000
FPEWITIPLV CIYMLSTNIL LVNLLVAMFG YTVGIVQENN DQVWKFQRYF
1010 1020 1030 1040 1050
LVQEYCNRLN IPFPFVVFAY FYMVVKKCFK CCCKEKNMES NACCFRNEDN
1060 1070 1080 1090 1100
ETLAWEGVMK ENYLVKINTK ANDNSEEMRH RFRQLDSKLN DLKSLLKEIA
NNIK
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF481480 mRNA Translation: AAL79553.1 AY095352 mRNA Translation: AAM23261.1 AC087780 Genomic DNA No translation available. AC102505 Genomic DNA No translation available. CH466520 Genomic DNA Translation: EDL40112.1 BC117934 mRNA Translation: AAI17935.1 |
CCDSi | CCDS48316.1 |
RefSeqi | NP_599013.1, NM_134252.3 XP_006529288.1, XM_006529225.1 XP_006529289.1, XM_006529226.1 |
UniGenei | Mm.218753 |
Genome annotation databases
Ensembli | ENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251 ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251 ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251 |
GeneIDi | 171382 |
KEGGi | mmu:171382 |
UCSCi | uc029qrk.1 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF481480 mRNA Translation: AAL79553.1 AY095352 mRNA Translation: AAM23261.1 AC087780 Genomic DNA No translation available. AC102505 Genomic DNA No translation available. CH466520 Genomic DNA Translation: EDL40112.1 BC117934 mRNA Translation: AAI17935.1 |
CCDSi | CCDS48316.1 |
RefSeqi | NP_599013.1, NM_134252.3 XP_006529288.1, XM_006529225.1 XP_006529289.1, XM_006529226.1 |
UniGenei | Mm.218753 |
3D structure databases
ProteinModelPortali | Q8R4D5 |
SMRi | Q8R4D5 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 228590, 1 interactor |
DIPi | DIP-61852N |
IntActi | Q8R4D5, 1 interactor |
STRINGi | 10090.ENSMUSP00000036991 |
Chemistry databases
BindingDBi | Q8R4D5 |
ChEMBLi | CHEMBL3108632 |
GuidetoPHARMACOLOGYi | 500 |
PTM databases
iPTMneti | Q8R4D5 |
PhosphoSitePlusi | Q8R4D5 |
SwissPalmi | Q8R4D5 |
Proteomic databases
PaxDbi | Q8R4D5 |
PRIDEi | Q8R4D5 |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251 ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251 ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251 |
GeneIDi | 171382 |
KEGGi | mmu:171382 |
UCSCi | uc029qrk.1 mouse |
Organism-specific databases
CTDi | 79054 |
MGIi | MGI:2181435 Trpm8 |
Phylogenomic databases
eggNOGi | ENOG410KCTC Eukaryota ENOG4110YBY LUCA |
GeneTreei | ENSGT00940000160270 |
HOGENOMi | HOG000236350 |
HOVERGENi | HBG100888 |
InParanoidi | Q8R4D5 |
KOi | K04983 |
OMAi | YIMDDFT |
OrthoDBi | 738147at2759 |
PhylomeDBi | Q8R4D5 |
TreeFami | TF314204 |
Enzyme and pathway databases
Reactomei | R-MMU-3295583 TRP channels |
Miscellaneous databases
PROi | PR:Q8R4D5 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000036251 Expressed in 19 organ(s), highest expression level in dorsal root ganglion |
Genevisiblei | Q8R4D5 MM |
Family and domain databases
InterProi | View protein in InterPro IPR029603 TRPM8 |
PANTHERi | PTHR13800:SF9 PTHR13800:SF9, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | TRPM8_MOUSE | |
Accessioni | Q8R4D5Primary (citable) accession number: Q8R4D5 Secondary accession number(s): E9Q165, Q148W9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 21, 2004 |
Last sequence update: | February 6, 2013 | |
Last modified: | February 13, 2019 | |
This is version 112 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot