TRPM8_MOUSE
ID TRPM8_MOUSE Reviewed; 1104 AA.
AC Q8R4D5; E9Q165; Q148W9;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 3.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 8;
DE AltName: Full=Long transient receptor potential channel 6;
DE Short=LTrpC-6;
DE Short=LTrpC6;
DE AltName: Full=Transient receptor potential p8;
DE Short=Trp-p8;
GN Name=Trpm8; Synonyms=Ltrpc6, Trpp8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PROBABLE SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Spinal ganglion;
RX PubMed=11893340; DOI=10.1016/s0092-8674(02)00652-9;
RA Peier A.M., Moqrich A., Hergarden A.C., Reeve A.J., Andersson D.A.,
RA Story G.M., Earley T.J., Dragoni I., McIntyre P., Bevan S., Patapoutian A.;
RT "A TRP channel that senses cold stimuli and menthol.";
RL Cell 108:705-715(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Tsavaler L., Laus R.;
RT "The murine homologue of TRPM8(Trpp8) gene: cloning, sequencing and tissue
RT distribution.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 168-175, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=12654248; DOI=10.1016/s0092-8674(03)00158-2;
RA Story G.M., Peier A.M., Reeve A.J., Eid S.R., Mosbacher J., Hricik T.R.,
RA Earley T.J., Hergarden A.C., Anderson D.A., Hwang S.W., McIntyre P.,
RA Jegla T., Bevan S., Patapoutian A.;
RT "ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated
RT by cold temperatures.";
RL Cell 112:819-829(2003).
RN [8]
RP FUNCTION.
RX PubMed=15190109; DOI=10.1523/jneurosci.0890-04.2004;
RA Andersson D.A., Chase H.W., Bevan S.;
RT "TRPM8 activation by menthol, icilin, and cold is differentially modulated
RT by intracellular pH.";
RL J. Neurosci. 24:5364-5369(2004).
RN [9]
RP SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-934, AND MUTAGENESIS OF
RP ASN-821; CYS-929; ASN-934 AND CYS-940.
RX PubMed=17015441; DOI=10.1074/jbc.m607227200;
RA Dragoni I., Guida E., McIntyre P.;
RT "The cold and menthol receptor TRPM8 contains a functionally important
RT double cysteine motif.";
RL J. Biol. Chem. 281:37353-37360(2006).
RN [10]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-934, AND MUTAGENESIS OF ASN-934.
RX PubMed=19176480; DOI=10.1074/jbc.m807228200;
RA Morenilla-Palao C., Pertusa M., Meseguer V., Cabedo H., Viana F.;
RT "Lipid raft segregation modulates TRPM8 channel activity.";
RL J. Biol. Chem. 284:9215-9224(2009).
RN [11]
RP ROLE OF GLYCOSYLATION IN CHANNEL ACTIVITY, AND MUTAGENESIS OF ASN-934.
RX PubMed=22493431; DOI=10.1074/jbc.m111.312645;
RA Pertusa M., Madrid R., Morenilla-Palao C., Belmonte C., Viana F.;
RT "N-glycosylation of TRPM8 ion channels modulates temperature sensitivity of
RT cold thermoreceptor neurons.";
RL J. Biol. Chem. 287:18218-18229(2012).
CC -!- FUNCTION: Receptor-activated non-selective cation channel involved in
CC detection of sensations such as coolness, by being activated by cold
CC temperature below 25 degrees Celsius. Activated by icilin, eucalyptol,
CC menthol, cold and modulation of intracellular pH. Involved in menthol
CC sensation. Permeable for monovalent cations sodium, potassium, and
CC cesium and divalent cation calcium. Temperature sensing is tightly
CC linked to voltage-dependent gating. Activated upon depolarization,
CC changes in temperature resulting in graded shifts of its voltage-
CC dependent activation curves. The chemical agonists menthol functions as
CC a gating modifier, shifting activation curves towards physiological
CC membrane potentials. Temperature sensitivity arises from a tenfold
CC difference in the activation energies associated with voltage-dependent
CC opening and closing. {ECO:0000269|PubMed:11893340,
CC ECO:0000269|PubMed:15190109}.
CC -!- SUBUNIT: Interacts (via N-terminus and C-terminus domains) with TCAF1;
CC the interaction stimulates TRPM8 channel activity. Interacts (via N-
CC terminus and C-terminus domains) with TCAF2; the interaction inhibits
CC TRPM8 channel activity (By similarity). Homotetramer.
CC {ECO:0000250|UniProtKB:Q7Z2W7, ECO:0000269|PubMed:17015441}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Membrane raft. Note=Localizes to membrane rafts but is also located in
CC the cell membrane outside of these regions where channel response to
CC cold is enhanced compared to membrane rafts.
CC -!- TISSUE SPECIFICITY: Expressed in dorsal root and trigeminal ganglia.
CC Specifically expressed in a subset of pain- and temperature-sensing
CC neurons. Not expressed in heavily myelinated neurons. Not expressed in
CC neurons expressing TRPA1 or TRPV1. {ECO:0000269|PubMed:11893340,
CC ECO:0000269|PubMed:12654248}.
CC -!- DOMAIN: The coiled coil region is required for multimerization.
CC {ECO:0000250}.
CC -!- PTM: N-glycosylation is not essential for but facilitates cell surface
CC expression, multimerization, association with lipid rafts and ion
CC channel activity. {ECO:0000269|PubMed:17015441,
CC ECO:0000269|PubMed:19176480}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC subfamily. TRPM8 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF481480; AAL79553.1; -; mRNA.
DR EMBL; AY095352; AAM23261.1; -; mRNA.
DR EMBL; AC087780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC102505; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466520; EDL40112.1; -; Genomic_DNA.
DR EMBL; BC117934; AAI17935.1; -; mRNA.
DR CCDS; CCDS48316.1; -.
DR RefSeq; NP_599013.1; NM_134252.3.
DR RefSeq; XP_006529288.1; XM_006529225.1.
DR RefSeq; XP_006529289.1; XM_006529226.1.
DR AlphaFoldDB; Q8R4D5; -.
DR SMR; Q8R4D5; -.
DR BioGRID; 228590; 1.
DR DIP; DIP-61852N; -.
DR IntAct; Q8R4D5; 1.
DR STRING; 10090.ENSMUSP00000036991; -.
DR BindingDB; Q8R4D5; -.
DR ChEMBL; CHEMBL3108632; -.
DR DrugCentral; Q8R4D5; -.
DR GuidetoPHARMACOLOGY; 500; -.
DR GlyGen; Q8R4D5; 1 site.
DR iPTMnet; Q8R4D5; -.
DR PhosphoSitePlus; Q8R4D5; -.
DR SwissPalm; Q8R4D5; -.
DR PaxDb; Q8R4D5; -.
DR PRIDE; Q8R4D5; -.
DR Antibodypedia; 20244; 502 antibodies from 37 providers.
DR DNASU; 171382; -.
DR Ensembl; ENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251.
DR Ensembl; ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251.
DR Ensembl; ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251.
DR GeneID; 171382; -.
DR KEGG; mmu:171382; -.
DR UCSC; uc029qrk.1; mouse.
DR CTD; 79054; -.
DR MGI; MGI:2181435; Trpm8.
DR VEuPathDB; HostDB:ENSMUSG00000036251; -.
DR eggNOG; KOG3614; Eukaryota.
DR GeneTree; ENSGT00940000160270; -.
DR HOGENOM; CLU_001390_0_0_1; -.
DR InParanoid; Q8R4D5; -.
DR OMA; SFWKEER; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q8R4D5; -.
DR TreeFam; TF314204; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR BioGRID-ORCS; 171382; 0 hits in 74 CRISPR screens.
DR PRO; PR:Q8R4D5; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8R4D5; protein.
DR Bgee; ENSMUSG00000036251; Expressed in seminiferous tubule of testis and 5 other tissues.
DR Genevisible; Q8R4D5; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005262; F:calcium channel activity; IDA:MGI.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0005216; F:ion channel activity; IDA:MGI.
DR GO; GO:0099604; F:ligand-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:MGI.
DR GO; GO:0016048; P:detection of temperature stimulus; IEA:InterPro.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0009409; P:response to cold; IDA:MGI.
DR GO; GO:0009266; P:response to temperature stimulus; IDA:MGI.
DR GO; GO:0050955; P:thermoception; IDA:MGI.
DR InterPro; IPR029603; TRPM8.
DR InterPro; IPR041491; TRPM_SLOG.
DR PANTHER; PTHR13800:SF9; PTHR13800:SF9; 1.
DR Pfam; PF18139; LSDAT_euk; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Direct protein sequencing; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Reference proteome;
KW Sensory transduction; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1104
FT /note="Transient receptor potential cation channel
FT subfamily M member 8"
FT /id="PRO_0000215334"
FT TOPO_DOM 1..691
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 692..712
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 713..734
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 735..755
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 756..759
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 760..780
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..794
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 795..815
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 816..829
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 830..850
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 851..958
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 959..979
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 980..1104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1069..1104
FT /evidence="ECO:0000255"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:17015441,
FT ECO:0000269|PubMed:19176480"
FT MUTAGEN 821
FT /note="N->Q: No effect on glycosylation or ability to form
FT functional channels."
FT /evidence="ECO:0000269|PubMed:17015441"
FT MUTAGEN 929
FT /note="C->A: Abolishes ion channel activity. No effect on
FT cell surface expression. Reduced glycosylation."
FT /evidence="ECO:0000269|PubMed:17015441"
FT MUTAGEN 934
FT /note="N->D: Slighty reduced ion channel sensitivity to
FT cold stimuli. No significant effect on ion channel
FT sensitivity to menthol plus cold stimuli."
FT /evidence="ECO:0000269|PubMed:17015441,
FT ECO:0000269|PubMed:19176480, ECO:0000269|PubMed:22493431"
FT MUTAGEN 934
FT /note="N->K: Reduced ion channel sensitivity to cold
FT stimuli or menthol plus cold stimuli."
FT /evidence="ECO:0000269|PubMed:17015441,
FT ECO:0000269|PubMed:19176480, ECO:0000269|PubMed:22493431"
FT MUTAGEN 934
FT /note="N->Q: Abolishes glycosylation. Shifts threshold of
FT temperature activation from 26.5 to 24 degrees Celsius.
FT Reduced cell surface expression, association with lipid
FT rafts and response to cold."
FT /evidence="ECO:0000269|PubMed:17015441,
FT ECO:0000269|PubMed:19176480, ECO:0000269|PubMed:22493431"
FT MUTAGEN 940
FT /note="C->A: Abolishes ion channel activity. No effect on
FT cell surface expression. Reduced glycosylation."
FT /evidence="ECO:0000269|PubMed:17015441"
SQ SEQUENCE 1104 AA; 127710 MW; 16B5D6FBED2BE96D CRC64;
MSFEGARLSM RSRRNGTMGS TRTLYSSVSR STDVSYSDSD LVNFIQANFK KRECVFFTRD
SKAMENICKC GYAQSQHIEG TQINQNEKWN YKKHTKEFPT DAFGDIQFET LGKKGKYLRL
SCDTDSETLY ELLTQHWHLK TPNLVISVTG GAKNFALKPR MRKIFSRLIY IAQSKGAWIL
TGGTHYGLMK YIGEVVRDNT ISRNSEENIV AIGIAAWGMV SNRDTLIRSC DDEGHFSAQY
IMDDFTRDPL YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTS QDSNYGGKIP
IVCFAQGGGR ETLKAINTSV KSKIPCVVVE GSGQIADVIA SLVEVEDVLT SSMVKEKLVR
FLPRTVSRLP EEEIESWIKW LKEILESSHL LTVIKMEEAG DEIVSNAISY ALYKAFSTNE
QDKDNWNGQL KLLLEWNQLD LASDEIFTND RRWESADLQE VMFTALIKDR PKFVRLFLEN
GLNLQKFLTN EVLTELFSTH FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRSFWKEDR
SSREDLDVEL HDASLTTRHP LQALFIWAIL QNKKELSKVI WEQTKGCTLA ALGASKLLKT
LAKVKNDINA AGESEELANE YETRAVELFT ECYSNDEDLA EQLLVYSCEA WGGSNCLELA
VEATDQHFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF IIPLVGCGLV SFRKKPIDKH
KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL LFAYVLLMDF HSVPHTPELI LYALVFVLFC
DEVRQWYMNG VNYFTDLWNV MDTLGLFYFI AGIVFRLHSS NKSSLYSGRV IFCLDYIIFT
LRLIHIFTVS RNLGPKIIML QRMLIDVFFF LFLFAVWMVA FGVARQGILR QNEQRWRWIF
RSVIYEPYLA MFGQVPSDVD STTYDFSHCT FSGNESKPLC VELDEHNLPR FPEWITIPLV
CIYMLSTNIL LVNLLVAMFG YTVGIVQENN DQVWKFQRYF LVQEYCNRLN IPFPFVVFAY
FYMVVKKCFK CCCKEKNMES NACCFRNEDN ETLAWEGVMK ENYLVKINTK ANDNSEEMRH
RFRQLDSKLN DLKSLLKEIA NNIK
