TRPM8_RAT
ID TRPM8_RAT Reviewed; 1104 AA.
AC Q8R455;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 4.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 8;
DE AltName: Full=Cold menthol receptor 1;
GN Name=Trpm8; Synonyms=Cmr1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Trigeminal ganglion;
RX PubMed=11882888; DOI=10.1038/nature719;
RA McKemy D.D., Neuhausser W.M., Julius D.;
RT "Identification of a cold receptor reveals a general role for TRP channels
RT in thermosensation.";
RL Nature 416:52-58(2002).
RN [2]
RP SEQUENCE REVISION TO 449.
RC TISSUE=Trigeminal ganglion;
RA McKemy D.D., Neuhausser W.M., Julius D.;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=12634279; DOI=10.1152/jn.00843.2002;
RA Nealen M.L., Gold M.S., Thut P.D., Caterina M.J.;
RT "TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons
RT from rat.";
RL J. Neurophysiol. 90:515-520(2003).
RN [4]
RP SUBCELLULAR LOCATION.
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 [5]
RP SUBUNIT.
RX PubMed=20214891; DOI=10.1016/j.bbrc.2010.03.027;
RA Stewart A.P., Egressy K., Lim A., Edwardson J.M.;
RT "AFM imaging reveals the tetrameric structure of the TRPM8 channel.";
RL Biochem. Biophys. Res. Commun. 394:383-386(2010).
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:11882888}.
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:20214891}.
CC -!- INTERACTION:
CC Q8R455; P50148: GNAQ; Xeno; NbExp=4; IntAct=EBI-15993527, EBI-3909604;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Membrane raft {ECO:0000269|PubMed:19176480}.
CC Note=Localizes to membrane rafts but is also located in the cell
CC membrane outside of these regions where channel response to cold is
CC enhanced compared to membrane rafts. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in dorsal root and trigeminal ganglia.
CC Specifically expressed in a subset of sensory neurons, including cold-
CC sensitive neurons in trigeminal neurons. {ECO:0000269|PubMed:11882888,
CC ECO:0000269|PubMed:12634279}.
CC -!- DOMAIN: The coiled coil region is required for multimerization.
CC {ECO:0000250}.
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; AY072788; AAL68394.2; -; mRNA.
DR RefSeq; NP_599198.2; NM_134371.2.
DR AlphaFoldDB; Q8R455; -.
DR SMR; Q8R455; -.
DR DIP; DIP-61851N; -.
DR IntAct; Q8R455; 1.
DR STRING; 10116.ENSRNOP00000025879; -.
DR BindingDB; Q8R455; -.
DR ChEMBL; CHEMBL5011; -.
DR DrugCentral; Q8R455; -.
DR GuidetoPHARMACOLOGY; 500; -.
DR PhosphoSitePlus; Q8R455; -.
DR PaxDb; Q8R455; -.
DR Ensembl; ENSRNOT00000025879; ENSRNOP00000025879; ENSRNOG00000019035.
DR GeneID; 171384; -.
DR KEGG; rno:171384; -.
DR CTD; 79054; -.
DR RGD; 620762; Trpm8.
DR eggNOG; KOG3614; Eukaryota.
DR GeneTree; ENSGT00940000160270; -.
DR HOGENOM; CLU_001390_0_0_1; -.
DR InParanoid; Q8R455; -.
DR OMA; SFWKEER; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q8R455; -.
DR TreeFam; TF314204; -.
DR Reactome; R-RNO-3295583; TRP channels.
DR PRO; PR:Q8R455; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000019035; Expressed in ovary and 2 other tissues.
DR Genevisible; Q8R455; RN.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005262; F:calcium channel activity; ISO:RGD.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005216; F:ion channel activity; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0016048; P:detection of temperature stimulus; IEA:InterPro.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0009409; P:response to cold; IDA:RGD.
DR GO; GO:0009266; P:response to temperature stimulus; ISO:RGD.
DR GO; GO:0050955; P:thermoception; ISO:RGD.
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; Ion channel; Ion transport; Membrane;
KW Reference proteome; Sensory transduction; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1104
FT /note="Transient receptor potential cation channel
FT subfamily M member 8"
FT /id="PRO_0000215335"
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..793
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 794..814
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 815..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 COILED 1067..1104
FT /evidence="ECO:0000255"
SQ SEQUENCE 1104 AA; 127629 MW; D07BFF14EB23970A CRC64;
MSFEGARLSM RSRRNGTLGS TRTLYSSVSR STDVSYSESD LVNFIQANFK KRECVFFTRD
SKAMESICKC GYAQSQHIEG TQINQNEKWN YKKHTKEFPT DAFGDIQFET LGKKGKYLRL
SCDTDSETLY ELLTQHWHLK TPNLVISVTG GAKNFALKPR MRKIFSRLIY IAQSKGAWIL
TGGTHYGLMK YIGEVVRDNT ISRNSEENIV AIGIAAWGMV SNRDTLIRNC DDEGHFSAQY
IMDDFMRDPL YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTS QDSNYGGKIP
IVCFAQGGGR ETLKAINTSV KSKIPCVVVE GSGQIADVIA SLVEVEDVLT SSMVKEKLVR
FLPRTVSRLP EEEIESWIKW LKEILESPHL LTVIKMEEAG DEVVSSAISY ALYKAFSTNE
QDKDNWNGQL KLLLEWNQLD LASDEIFTND RRWESADLQE VMFTALIKDR PKFVRLFLEN
GLNLQKFLTN EVLTELFSTH FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRSFWKEDR
SSREDLDVEL HDASLTTRHP LQALFIWAIL QNKKELSKVI WEQTKGCTLA ALGASKLLKT
LAKVKNDINA AGESEELANE YETRAVELFT ECYSSDEDLA 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 VELDEYNLPR FPEWITIPLV
CIYMLSTNIL LVNLLVAMFG YTVGIVQENN DQVWKFQRYF LVQEYCNRLN IPFPFVVFAY
FYMVVKKCFK CCCKEKNTES SACCFRNEDN ETLAWEGVMK ENYLVKINTK ANDNAEEMRH
RFRQLDTKLN DLKGLLKEIA NKIK
