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Protein

Transient receptor potential cation channel subfamily M member 8

Gene

Trpm8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Keywordsi

Molecular functionIon channel
Biological processIon transport, Sensory transduction, Transport

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily M member 8
Alternative 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2181435 Trpm8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 691CytoplasmicSequence analysisAdd BLAST691
Transmembranei692 – 712Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini713 – 734ExtracellularSequence analysisAdd BLAST22
Transmembranei735 – 755Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini756 – 759CytoplasmicSequence analysis4
Transmembranei760 – 780Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini781 – 794ExtracellularSequence analysisAdd BLAST14
Transmembranei795 – 815Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini816 – 829CytoplasmicSequence analysisAdd BLAST14
Transmembranei830 – 850Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini851 – 958ExtracellularSequence analysisAdd BLAST108
Transmembranei959 – 979Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini980 – 1104CytoplasmicSequence analysisAdd BLAST125

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi821N → Q: No effect on glycosylation or ability to form functional channels. 1 Publication1
Mutagenesisi929C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication1
Mutagenesisi934N → D: Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli. 3 Publications1
Mutagenesisi934N → K: Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli. 3 Publications1
Mutagenesisi934N → 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 Publications1
Mutagenesisi940C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3108632
GuidetoPHARMACOLOGYi500

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153341 – 1104Transient receptor potential cation channel subfamily M member 8Add BLAST1104

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi934N-linked (GlcNAc...) (complex) asparagine2 Publications1

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

Glycoprotein

Proteomic databases

PaxDbiQ8R4D5
PRIDEiQ8R4D5

PTM databases

iPTMnetiQ8R4D5
PhosphoSitePlusiQ8R4D5
SwissPalmiQ8R4D5

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

BgeeiENSMUSG00000036251 Expressed in 19 organ(s), highest expression level in dorsal root ganglion
GenevisibleiQ8R4D5 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-protein interaction databases

BioGridi228590, 1 interactor
DIPiDIP-61852N
IntActiQ8R4D5, 1 interactor
STRINGi10090.ENSMUSP00000036991

Chemistry databases

BindingDBiQ8R4D5

Structurei

3D structure databases

ProteinModelPortaliQ8R4D5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1069 – 1104Sequence analysisAdd BLAST36

Domaini

The coiled coil region is required for multimerization.By similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410KCTC Eukaryota
ENOG4110YBY LUCA
GeneTreeiENSGT00760000119127
HOGENOMiHOG000236350
HOVERGENiHBG100888
InParanoidiQ8R4D5
KOiK04983
OMAiETLAWEG
OrthoDBiEOG091G035A
PhylomeDBiQ8R4D5
TreeFamiTF314204

Family and domain databases

InterProiView protein in InterPro
IPR029603 TRPM8
PANTHERiPTHR13800:SF9 PTHR13800:SF9, 1 hit

Sequencei

Sequence statusi: Complete.

Q8R4D5-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:1,104
Mass (Da):127,710
Last modified:February 6, 2013 - v3
Checksum:i16B5D6FBED2BE96D
GO

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
CCDSiCCDS48316.1
RefSeqiNP_599013.1, NM_134252.3
XP_006529288.1, XM_006529225.1
XP_006529289.1, XM_006529226.1
UniGeneiMm.218753

Genome annotation databases

EnsembliENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251
ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251
ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251
GeneIDi171382
KEGGimmu:171382
UCSCiuc029qrk.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
CCDSiCCDS48316.1
RefSeqiNP_599013.1, NM_134252.3
XP_006529288.1, XM_006529225.1
XP_006529289.1, XM_006529226.1
UniGeneiMm.218753

3D structure databases

ProteinModelPortaliQ8R4D5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi228590, 1 interactor
DIPiDIP-61852N
IntActiQ8R4D5, 1 interactor
STRINGi10090.ENSMUSP00000036991

Chemistry databases

BindingDBiQ8R4D5
ChEMBLiCHEMBL3108632
GuidetoPHARMACOLOGYi500

PTM databases

iPTMnetiQ8R4D5
PhosphoSitePlusiQ8R4D5
SwissPalmiQ8R4D5

Proteomic databases

PaxDbiQ8R4D5
PRIDEiQ8R4D5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251
ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251
ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251
GeneIDi171382
KEGGimmu:171382
UCSCiuc029qrk.1 mouse

Organism-specific databases

CTDi79054
MGIiMGI:2181435 Trpm8

Phylogenomic databases

eggNOGiENOG410KCTC Eukaryota
ENOG4110YBY LUCA
GeneTreeiENSGT00760000119127
HOGENOMiHOG000236350
HOVERGENiHBG100888
InParanoidiQ8R4D5
KOiK04983
OMAiETLAWEG
OrthoDBiEOG091G035A
PhylomeDBiQ8R4D5
TreeFamiTF314204

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Miscellaneous databases

PROiPR:Q8R4D5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036251 Expressed in 19 organ(s), highest expression level in dorsal root ganglion
GenevisibleiQ8R4D5 MM

Family and domain databases

InterProiView protein in InterPro
IPR029603 TRPM8
PANTHERiPTHR13800:SF9 PTHR13800:SF9, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRPM8_MOUSE
AccessioniPrimary (citable) accession number: Q8R4D5
Secondary accession number(s): E9Q165, Q148W9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: February 6, 2013
Last modified: September 12, 2018
This is version 108 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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