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Q8R4D5 (TRPM8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Trpm8
Synonyms:Ltrpc6, Trpp8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length1104 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.8

Subunit structure

Homotetramer. Ref.9

Subcellular location

Cell membrane; Multi-pass membrane protein. Membrane raft. 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. Ref.1 Ref.9 Ref.10

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. Ref.1 Ref.7

Domain

The coiled coil region is required for multimerization By similarity.

Post-translational modification

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

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM8 sub-subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11041104Transient receptor potential cation channel subfamily M member 8
PRO_0000215334

Regions

Topological domain1 – 691691Cytoplasmic Potential
Transmembrane692 – 71221Helical; Name=1; Potential
Topological domain713 – 73422Extracellular Potential
Transmembrane735 – 75521Helical; Name=2; Potential
Topological domain756 – 7594Cytoplasmic Potential
Transmembrane760 – 78021Helical; Name=3; Potential
Topological domain781 – 79414Extracellular Potential
Transmembrane795 – 81521Helical; Name=4; Potential
Topological domain816 – 82914Cytoplasmic Potential
Transmembrane830 – 85021Helical; Name=5; Potential
Topological domain851 – 958108Extracellular Potential
Transmembrane959 – 97921Helical; Name=6; Potential
Topological domain980 – 1104125Cytoplasmic Potential
Coiled coil1069 – 110436 Potential

Amino acid modifications

Glycosylation9341N-linked (GlcNAc...) (complex) Ref.9 Ref.10

Experimental info

Mutagenesis8211N → Q: No effect on glycosylation or ability to form functional channels. Ref.9
Mutagenesis9291C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. Ref.9
Mutagenesis9341N → D: Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli. Ref.9 Ref.10 Ref.11
Mutagenesis9341N → K: Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli. Ref.9 Ref.10 Ref.11
Mutagenesis9341N → 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. Ref.9 Ref.10 Ref.11
Mutagenesis9401C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q8R4D5 [UniParc].

Last modified February 6, 2013. Version 3.
Checksum: 16B5D6FBED2BE96D

FASTA1,104127,710
        10         20         30         40         50         60 
MSFEGARLSM RSRRNGTMGS TRTLYSSVSR STDVSYSDSD LVNFIQANFK KRECVFFTRD 

        70         80         90        100        110        120 
SKAMENICKC GYAQSQHIEG TQINQNEKWN YKKHTKEFPT DAFGDIQFET LGKKGKYLRL 

       130        140        150        160        170        180 
SCDTDSETLY ELLTQHWHLK TPNLVISVTG GAKNFALKPR MRKIFSRLIY IAQSKGAWIL 

       190        200        210        220        230        240 
TGGTHYGLMK YIGEVVRDNT ISRNSEENIV AIGIAAWGMV SNRDTLIRSC DDEGHFSAQY 

       250        260        270        280        290        300 
IMDDFTRDPL YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTS QDSNYGGKIP 

       310        320        330        340        350        360 
IVCFAQGGGR ETLKAINTSV KSKIPCVVVE GSGQIADVIA SLVEVEDVLT SSMVKEKLVR 

       370        380        390        400        410        420 
FLPRTVSRLP EEEIESWIKW LKEILESSHL LTVIKMEEAG DEIVSNAISY ALYKAFSTNE 

       430        440        450        460        470        480 
QDKDNWNGQL KLLLEWNQLD LASDEIFTND RRWESADLQE VMFTALIKDR PKFVRLFLEN 

       490        500        510        520        530        540 
GLNLQKFLTN EVLTELFSTH FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRSFWKEDR 

       550        560        570        580        590        600 
SSREDLDVEL HDASLTTRHP LQALFIWAIL QNKKELSKVI WEQTKGCTLA ALGASKLLKT 

       610        620        630        640        650        660 
LAKVKNDINA AGESEELANE YETRAVELFT ECYSNDEDLA EQLLVYSCEA WGGSNCLELA 

       670        680        690        700        710        720 
VEATDQHFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF IIPLVGCGLV SFRKKPIDKH 

       730        740        750        760        770        780 
KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL LFAYVLLMDF HSVPHTPELI LYALVFVLFC 

       790        800        810        820        830        840 
DEVRQWYMNG VNYFTDLWNV MDTLGLFYFI AGIVFRLHSS NKSSLYSGRV IFCLDYIIFT 

       850        860        870        880        890        900 
LRLIHIFTVS RNLGPKIIML QRMLIDVFFF LFLFAVWMVA FGVARQGILR QNEQRWRWIF 

       910        920        930        940        950        960 
RSVIYEPYLA MFGQVPSDVD STTYDFSHCT FSGNESKPLC VELDEHNLPR FPEWITIPLV 

       970        980        990       1000       1010       1020 
CIYMLSTNIL LVNLLVAMFG YTVGIVQENN DQVWKFQRYF LVQEYCNRLN IPFPFVVFAY 

      1030       1040       1050       1060       1070       1080 
FYMVVKKCFK CCCKEKNMES NACCFRNEDN ETLAWEGVMK ENYLVKINTK ANDNSEEMRH 

      1090       1100 
RFRQLDSKLN DLKSLLKEIA NNIK

« Hide

References

« Hide 'large scale' references
[1]"A TRP channel that senses cold stimuli and menthol."
Peier A.M., Moqrich A., Hergarden A.C., Reeve A.J., Andersson D.A., Story G.M., Earley T.J., Dragoni I., McIntyre P., Bevan S., Patapoutian A.
Cell 108:705-715(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PROBABLE SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: C57BL/6.
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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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, 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]"Lipid raft segregation modulates TRPM8 channel activity."
Morenilla-Palao C., Pertusa M., Meseguer V., Cabedo H., Viana F.
J. Biol. Chem. 284:9215-9224(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00153878.
RefSeqNP_599013.1. NM_134252.3.
UniGeneMm.218753.

3D structure databases

ProteinModelPortalQ8R4D5.
ModBaseSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000108739.

PTM databases

PhosphoSiteQ8R4D5.

Proteomic databases

PRIDEQ8R4D5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251.
ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251.
ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251.
GeneID171382.
KEGGmmu:171382.

Organism-specific databases

CTD79054.
MGIMGI:2181435. Trpm8.

Phylogenomic databases

eggNOGNOG253824.
GeneTreeENSGT00650000093200.
HOGENOMHOG000236350.
HOVERGENHBG100888.
InParanoidQ8R4D5.
KOK04983.
OMADFAHCTF.
OrthoDBEOG4SJ5D0.

Gene expression databases

ArrayExpressQ8R4D5.
BgeeQ8R4D5.
GenevestigatorQ8R4D5.
GermOnlineENSMUSG00000036251. Mus musculus.

Family and domain databases

InterProIPR005821. Ion_trans_dom.
[Graphical view]
PfamPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio370973.
SOURCESearch...

Entry information

Entry nameTRPM8_MOUSE
AccessionPrimary (citable) accession number: Q8R4D5
Secondary accession number(s): E9Q165, Q148W9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: February 6, 2013
Last modified: May 1, 2013
This is version 74 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents