Trpm8

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
Inferred from direct assayⁱ
ion channel activity
Source: MGI
Inferred from direct assayⁱ
- 15194687
protein homodimerization activity
Source: MGI
Inferred from physical interactionⁱ
- 17015441

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

calcium ion transport
Source: MGI
Inferred from direct assayⁱ
- 17015441
cellular calcium ion homeostasis
Source: MGI
Inferred from direct assayⁱ
- 11893340
detection of temperature stimulus Source: InterPro
positive regulation of cold-induced thermogenesis
Source: YuBioLab
Inferred from mutant phenotypeⁱ
- 22241835
protein homotetramerization
Source: MGI
Inferred from direct assayⁱ
- 17015441
protein homotrimerization
Source: MGI
Inferred from direct assayⁱ
- 17015441
response to cold
Source: MGI
Inferred from direct assayⁱ
- 12654248
- 17015441
response to temperature stimulus
Source: MGI
Inferred from direct assayⁱ
- 11893340
thermoception
Source: MGI
Inferred from direct assayⁱ
- 12654248

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Ion channel
Biological process	Ion transport, Sensory transduction, Transport

Enzyme and pathway databases

Reactomeⁱ	R-MMU-3295583 TRP channels

Reactomeⁱ

R-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
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 1

Organism-specific databases

MGIⁱ	MGI:2181435 Trpm8

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 691	CytoplasmicSequence analysisAdd BLAST	691
Transmembraneⁱ	692 – 712	Helical; Name=1Sequence analysisAdd BLAST	21
Topological domainⁱ	713 – 734	ExtracellularSequence analysisAdd BLAST	22
Transmembraneⁱ	735 – 755	Helical; Name=2Sequence analysisAdd BLAST	21
Topological domainⁱ	756 – 759	CytoplasmicSequence analysis	4
Transmembraneⁱ	760 – 780	Helical; Name=3Sequence analysisAdd BLAST	21
Topological domainⁱ	781 – 794	ExtracellularSequence analysisAdd BLAST	14
Transmembraneⁱ	795 – 815	Helical; Name=4Sequence analysisAdd BLAST	21
Topological domainⁱ	816 – 829	CytoplasmicSequence analysisAdd BLAST	14
Transmembraneⁱ	830 – 850	Helical; Name=5Sequence analysisAdd BLAST	21
Topological domainⁱ	851 – 958	ExtracellularSequence analysisAdd BLAST	108
Transmembraneⁱ	959 – 979	Helical; Name=6Sequence analysisAdd BLAST	21
Topological domainⁱ	980 – 1104	CytoplasmicSequence analysisAdd BLAST	125

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	821	N → Q: No effect on glycosylation or ability to form functional channels. 1 Publication	1
Mutagenesisⁱ	929	C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication	1
Mutagenesisⁱ	934	N → D: Slighty reduced ion channel sensitivity to cold stimuli. No significant effect on ion channel sensitivity to menthol plus cold stimuli. 3 Publications	1
Mutagenesisⁱ	934	N → K: Reduced ion channel sensitivity to cold stimuli or menthol plus cold stimuli. 3 Publications	1
Mutagenesisⁱ	934	N → 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	1
Mutagenesisⁱ	940	C → A: Abolishes ion channel activity. No effect on cell surface expression. Reduced glycosylation. 1 Publication	1

Chemistry databases

ChEMBLⁱ	CHEMBL3108632
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	500

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000215334	1 – 1104	Transient receptor potential cation channel subfamily M member 8Add BLAST		1104

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Glycosylationⁱ	934	N-linked (GlcNAc...) (complex) asparagine2 Publications		1

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

PaxDbⁱ	Q8R4D5
PRIDEⁱ	Q8R4D5

PTM databases

iPTMnetⁱ	Q8R4D5
PhosphoSitePlusⁱ	Q8R4D5
SwissPalmⁱ	Q8R4D5

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

Bgeeⁱ	ENSMUSG00000036251 Expressed in 19 organ(s), highest expression level in dorsal root ganglion
Genevisibleⁱ	Q8R4D5 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
Inferred from physical interactionⁱ
- 17015441

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	228590, 1 interactor
Database of interacting proteins More...DIPⁱ	DIP-61852N
IntActⁱ	Q8R4D5, 1 interactor
STRINGⁱ	10090.ENSMUSP00000036991

Chemistry databases

BindingDBⁱ

Q8R4D5

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q8R4D5
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	1069 – 1104	Sequence analysisAdd BLAST		36

Domainⁱ

The coiled coil region is required for multimerization.By similarity

Sequence similaritiesⁱ

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

Keywords - Domainⁱ

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG410KCTC Eukaryota ENOG4110YBY LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119127
HOGENOMⁱ	HOG000236350
HOVERGENⁱ	HBG100888
InParanoidⁱ	Q8R4D5
KEGG Orthology (KO) More...KOⁱ	K04983
OMAⁱ	ETLAWEG
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G035A
PhylomeDBⁱ	Q8R4D5
TreeFamⁱ	TF314204

Family and domain databases

InterProⁱ	View protein in InterPro IPR029603 TRPM8
PANTHERⁱ	PTHR13800:SF9 PTHR13800:SF9, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q8R4D5-1 [UniParc]FASTA Add 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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS48316.1
NCBI Reference Sequences More...RefSeqⁱ	NP_599013.1, NM_134252.3 XP_006529288.1, XM_006529225.1 XP_006529289.1, XM_006529226.1
UniGeneⁱ	Mm.218753

Genome annotation databases

Ensemblⁱ	ENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251 ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251 ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251
GeneIDⁱ	171382
KEGGⁱ	mmu:171382
UCSC genome browser More...UCSCⁱ	uc029qrk.1 mouse

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q8R4D5	Transient receptor potential cation channel subfamily M member 8		RAT		1104	UniRef90_Q8R4D5
Transient receptor potential cation channel subfamily M member 8		HETGA		1131
Transient receptor potential cation channel subfamily M member 8		AOTNA		1115
Transient receptor potential cation channel subfamily M member 8		CERAT		1115
transient receptor potential cation channel subfamily M member 8		Florida manatee		1112
+59

Protein	Similar proteins		Species	Score	Length	Source
Q8R4D5	Transient receptor potential cation channel subfamily M member 8		RAT		1104	UniRef50_Q8R4D5
Transient receptor potential cation channel subfamily M member 8		HETGA		1131
Transient receptor potential cation channel subfamily M member 8		AOTNA		1115
Transient receptor potential cation channel subfamily M member 8		CERAT		1115
transient receptor potential cation channel subfamily M member 8		Florida manatee		1112
+106

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
CCDSⁱ	CCDS48316.1
RefSeqⁱ	NP_599013.1, NM_134252.3 XP_006529288.1, XM_006529225.1 XP_006529289.1, XM_006529226.1
UniGeneⁱ	Mm.218753

3D structure databases

ProteinModelPortalⁱ	Q8R4D5
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	228590, 1 interactor
DIPⁱ	DIP-61852N
IntActⁱ	Q8R4D5, 1 interactor
STRINGⁱ	10090.ENSMUSP00000036991

Chemistry databases

BindingDBⁱ	Q8R4D5
ChEMBLⁱ	CHEMBL3108632
GuidetoPHARMACOLOGYⁱ	500

PTM databases

iPTMnetⁱ	Q8R4D5
PhosphoSitePlusⁱ	Q8R4D5
SwissPalmⁱ	Q8R4D5

Proteomic databases

PaxDbⁱ	Q8R4D5
PRIDEⁱ	Q8R4D5

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000040210; ENSMUSP00000036991; ENSMUSG00000036251 ENSMUST00000113114; ENSMUSP00000108739; ENSMUSG00000036251 ENSMUST00000171176; ENSMUSP00000131209; ENSMUSG00000036251
GeneIDⁱ	171382
KEGGⁱ	mmu:171382
UCSCⁱ	uc029qrk.1 mouse

Organism-specific databases

CTDⁱ	79054
MGIⁱ	MGI:2181435 Trpm8

Phylogenomic databases

eggNOGⁱ	ENOG410KCTC Eukaryota ENOG4110YBY LUCA
GeneTreeⁱ	ENSGT00760000119127
HOGENOMⁱ	HOG000236350
HOVERGENⁱ	HBG100888
InParanoidⁱ	Q8R4D5
KOⁱ	K04983
OMAⁱ	ETLAWEG
OrthoDBⁱ	EOG091G035A
PhylomeDBⁱ	Q8R4D5
TreeFamⁱ	TF314204

Enzyme and pathway databases

Reactomeⁱ	R-MMU-3295583 TRP channels

Reactomeⁱ

R-MMU-3295583 TRP channels

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q8R4D5
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000036251 Expressed in 19 organ(s), highest expression level in dorsal root ganglion
Genevisibleⁱ	Q8R4D5 MM

Family and domain databases

InterProⁱ	View protein in InterPro IPR029603 TRPM8
PANTHERⁱ	PTHR13800:SF9 PTHR13800:SF9, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TRPM8_MOUSE
Accessionⁱ	Q8R4D5Primary (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:	September 12, 2018
	This is version 108 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Direct protein sequencing, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q8R4D5 (TRPM8_MOUSE)

Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the ‘basket’ to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>

Transient receptor potential cation channel subfamily M member 8

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Other locations

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Coiled coil

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

UniProt is an ELIXIR core data resource

Your basket is currently empty. ⁱ

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ