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Protein

Transient receptor potential cation channel subfamily M member 8

Gene

Trpm8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • calcium ion transmembrane transport Source: GOC
  • calcium ion transport Source: MGI
  • cellular calcium ion homeostasis Source: MGI
  • detection of temperature stimulus Source: InterPro
  • ion transmembrane transport Source: GOC
  • protein homotetramerization Source: MGI
  • protein homotrimerization Source: MGI
  • response to cold Source: MGI
  • response to temperature stimulus Source: MGI
  • thermoception Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Ion 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2181435. Trpm8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 691691CytoplasmicSequence analysisAdd
BLAST
Transmembranei692 – 71221Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini713 – 73422ExtracellularSequence analysisAdd
BLAST
Transmembranei735 – 75521Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini756 – 7594CytoplasmicSequence analysis
Transmembranei760 – 78021Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini781 – 79414ExtracellularSequence analysisAdd
BLAST
Transmembranei795 – 81521Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini816 – 82914CytoplasmicSequence analysisAdd
BLAST
Transmembranei830 – 85021Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini851 – 958108ExtracellularSequence analysisAdd
BLAST
Transmembranei959 – 97921Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini980 – 1104125CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • external side of plasma membrane Source: MGI
  • integral component of membrane Source: MGI
  • membrane Source: MGI
  • membrane raft Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi821 – 8211N → Q: No effect on glycosylation or ability to form functional channels. 1 Publication
Mutagenesisi929 – 9291C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication
Mutagenesisi934 – 9341N → D: Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli. 3 Publications
Mutagenesisi934 – 9341N → K: Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli. 3 Publications
Mutagenesisi934 – 9341N → 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
Mutagenesisi940 – 9401C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication

Chemistry

ChEMBLiCHEMBL3108632.
GuidetoPHARMACOLOGYi500.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11041104Transient receptor potential cation channel subfamily M member 8PRO_0000215334Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi934 – 9341N-linked (GlcNAc...) (complex)2 Publications

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.
PhosphoSiteiQ8R4D5.
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

BgeeiQ8R4D5.
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 homodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi228590. 1 interaction.
MINTiMINT-4997805.
STRINGi10090.ENSMUSP00000036991.

Chemistry

BindingDBiQ8R4D5.

Structurei

3D structure databases

ProteinModelPortaliQ8R4D5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1069 – 110436Sequence analysisAdd
BLAST

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.
OMAiYIMDDFT.
OrthoDBiEOG725DH1.
PhylomeDBiQ8R4D5.
TreeFamiTF314204.

Family and domain databases

InterProiIPR029603. TRPM8.
[Graphical view]
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.

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 interaction.
MINTiMINT-4997805.
STRINGi10090.ENSMUSP00000036991.

Chemistry

BindingDBiQ8R4D5.
ChEMBLiCHEMBL3108632.
GuidetoPHARMACOLOGYi500.

PTM databases

iPTMnetiQ8R4D5.
PhosphoSiteiQ8R4D5.
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.
OMAiYIMDDFT.
OrthoDBiEOG725DH1.
PhylomeDBiQ8R4D5.
TreeFamiTF314204.

Enzyme and pathway databases

ReactomeiR-MMU-3295583. TRP channels.

Miscellaneous databases

PROiQ8R4D5.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R4D5.
GenevisibleiQ8R4D5. MM.

Family and domain databases

InterProiIPR029603. TRPM8.
[Graphical view]
PANTHERiPTHR13800:SF9. PTHR13800:SF9. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PROBABLE SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: C57BL/6J.
    Tissue: Spinal ganglion.
  2. "The murine homologue of TRPM8(Trpp8) gene: cloning, sequencing and tissue distribution."
    Tsavaler L., Laus R.
    Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (JAN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 168-175, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: OF1.
    Tissue: Hippocampus.
  7. "ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures."
    Story G.M., Peier A.M., Reeve A.J., Eid S.R., Mosbacher J., Hricik T.R., Earley T.J., Hergarden A.C., Anderson D.A., Hwang S.W., McIntyre P., Jegla T., Bevan S., Patapoutian A.
    Cell 112:819-829(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH."
    Andersson D.A., Chase H.W., Bevan S.
    J. Neurosci. 24:5364-5369(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The cold and menthol receptor TRPM8 contains a functionally important double cysteine motif."
    Dragoni I., Guida E., McIntyre P.
    J. Biol. Chem. 281:37353-37360(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-934, MUTAGENESIS OF ASN-821; CYS-929; ASN-934 AND CYS-940.
  10. Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-934, MUTAGENESIS OF ASN-934.
  11. "N-glycosylation of TRPM8 ion channels modulates temperature sensitivity of cold thermoreceptor neurons."
    Pertusa M., Madrid R., Morenilla-Palao C., Belmonte C., Viana F.
    J. Biol. Chem. 287:18218-18229(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE OF GLYCOSYLATION IN CHANNEL ACTIVITY, MUTAGENESIS OF ASN-934.

Entry informationi

Entry nameiTRPM8_MOUSE
AccessioniPrimary (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: June 8, 2016
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.