Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transient receptor potential cation channel subfamily M member 8

Gene

TRPM8

Organism
Homo sapiens (Human)
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 agonist 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. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration (PubMed:25559186). Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.4 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Ion transport, Sensory transduction, Transport

Enzyme and pathway databases

ReactomeiR-HSA-3295583. TRP channels.

Protein family/group databases

TCDBi1.A.4.5.7. the transient receptor potential ca(2+) channel (trp-cc) family.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:17961. TRPM8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 691CytoplasmicSequence analysisAdd BLAST691
Transmembranei692 – 712Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini713 – 734ExtracellularSequence analysisAdd BLAST22
Transmembranei735 – 755Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini756 – 759CytoplasmicSequence analysis4
Transmembranei760 – 780Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini781 – 794ExtracellularSequence analysisAdd BLAST14
Transmembranei795 – 815Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini816 – 829CytoplasmicSequence analysisAdd BLAST14
Transmembranei830 – 850Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini851 – 958ExtracellularSequence analysisAdd BLAST108
Transmembranei959 – 979Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini980 – 1104CytoplasmicSequence analysisAdd BLAST125

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi821N → Q: No effect on glycosylation or ability to form functional channels. 1 Publication1
Mutagenesisi934N → Q: Abolishes glycosylation. 1 Publication1
Mutagenesisi946H → N: No effect on glycosylation or channel activity. 1 Publication1
Mutagenesisi1089L → P: Abolishes multimerization and channel activity. Reduces cell surface expression. 1 Publication1

Organism-specific databases

DisGeNETi79054.
OpenTargetsiENSG00000144481.
PharmGKBiPA38270.

Chemistry databases

ChEMBLiCHEMBL1075319.
DrugBankiDB00825. Menthol.
GuidetoPHARMACOLOGYi500.

Polymorphism and mutation databases

BioMutaiTRPM8.
DMDMi143811469.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153331 – 1104Transient receptor potential cation channel subfamily M member 8Add BLAST1104

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi934N-linked (GlcNAc...) (complex)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ7Z2W7.
PRIDEiQ7Z2W7.

PTM databases

iPTMnetiQ7Z2W7.
PhosphoSitePlusiQ7Z2W7.

Expressioni

Tissue specificityi

Expressed in prostate. Also expressed in prostate tumors and in non-prostatic primary tumors such as colon, lung, breast and skin tumors.4 Publications

Gene expression databases

BgeeiENSG00000144481.
CleanExiHS_TRPM8.
ExpressionAtlasiQ7Z2W7. baseline and differential.
GenevisibleiQ7Z2W7. HS.

Interactioni

Subunit structurei

Homotetramer (By similarity). Isoform 2 and isoform 3 interact with the C-terminus of isoform 1 in a thermosensitive manner with decreased interaction at 21 degrees Celsius compared to 37 degrees Celsius. Interacts (via N-terminus and C-terminus domains) with TCAF1; the interaction stimulates TRPM8 channel activity (PubMed:25559186). Interacts (via N-terminus and C-terminus domains) with TCAF2 isoform 2; the interaction inhibits TRPM8 channel activity (PubMed:25559186).By similarity2 Publications

Protein-protein interaction databases

BioGridi122512. 11 interactors.
STRINGi9606.ENSP00000323926.

Chemistry databases

BindingDBiQ7Z2W7.

Structurei

3D structure databases

ProteinModelPortaliQ7Z2W7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni187 – 195Epitope; activates specific cytotoxic T lymphocytes9

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1071 – 1104Sequence analysisAdd BLAST34

Domaini

The coiled coil region is required for multimerization.2 Publications

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410INBX. Eukaryota.
ENOG4110YBY. LUCA.
GeneTreeiENSGT00760000119127.
HOGENOMiHOG000236350.
HOVERGENiHBG100888.
InParanoidiQ7Z2W7.
KOiK04983.
OMAiYIMDDFT.
OrthoDBiEOG091G035A.
PhylomeDBiQ7Z2W7.
TreeFamiTF314204.

Family and domain databases

InterProiIPR005821. Ion_trans_dom.
IPR029603. TRPM8.
[Graphical view]
PANTHERiPTHR13800:SF9. PTHR13800:SF9. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7Z2W7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSFRAARLSM RNRRNDTLDS TRTLYSSASR STDLSYSESD LVNFIQANFK
60 70 80 90 100
KRECVFFTKD SKATENVCKC GYAQSQHMEG TQINQSEKWN YKKHTKEFPT
110 120 130 140 150
DAFGDIQFET LGKKGKYIRL SCDTDAEILY ELLTQHWHLK TPNLVISVTG
160 170 180 190 200
GAKNFALKPR MRKIFSRLIY IAQSKGAWIL TGGTHYGLMK YIGEVVRDNT
210 220 230 240 250
ISRSSEENIV AIGIAAWGMV SNRDTLIRNC DAEGYFLAQY LMDDFTRDPL
260 270 280 290 300
YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTI QDSNYGGKIP
310 320 330 340 350
IVCFAQGGGK ETLKAINTSI KNKIPCVVVE GSGQIADVIA SLVEVEDALT
360 370 380 390 400
SSAVKEKLVR FLPRTVSRLP EEETESWIKW LKEILECSHL LTVIKMEEAG
410 420 430 440 450
DEIVSNAISY ALYKAFSTSE QDKDNWNGQL KLLLEWNQLD LANDEIFTND
460 470 480 490 500
RRWESADLQE VMFTALIKDR PKFVRLFLEN GLNLRKFLTH DVLTELFSNH
510 520 530 540 550
FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRGFRKEDR NGRDEMDIEL
560 570 580 590 600
HDVSPITRHP LQALFIWAIL QNKKELSKVI WEQTRGCTLA ALGASKLLKT
610 620 630 640 650
LAKVKNDINA AGESEELANE YETRAVELFT ECYSSDEDLA EQLLVYSCEA
660 670 680 690 700
WGGSNCLELA VEATDQHFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF
710 720 730 740 750
IIPLVGCGFV SFRKKPVDKH KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL
760 770 780 790 800
LFAYVLLMDF HSVPHPPELV LYSLVFVLFC DEVRQWYVNG 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 GTTYDFAHCT FTGNESKPLC VELDEHNLPR
960 970 980 990 1000
FPEWITIPLV CIYMLSTNIL LVNLLVAMFG YTVGTVQENN DQVWKFQRYF
1010 1020 1030 1040 1050
LVQEYCSRLN IPFPFIVFAY FYMVVKKCFK CCCKEKNMES SVCCFKNEDN
1060 1070 1080 1090 1100
ETLAWEGVMK ENYLVKINTK ANDTSEEMRH RFRQLDTKLN DLKGLLKEIA

NKIK
Length:1,104
Mass (Da):127,685
Last modified:April 3, 2007 - v2
Checksum:i5D88F5081EDFA632
GO
Isoform 2 (identifier: Q7Z2W7-2) [UniParc]FASTAAdd to basket
Also known as: sTRPM8-18, sM8-18

The sequence of this isoform differs from the canonical sequence as follows:
     1-188: Missing.
     234-242: GYFLAQYLM → VPVGQEEVC
     243-1104: Missing.

Show »
Length:54
Mass (Da):5,940
Checksum:i5DB74DAF67EBDCED
GO
Isoform 3 (identifier: Q7Z2W7-3) [UniParc]FASTAAdd to basket
Also known as: sTRPM8-6, sM8-6

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.
     234-242: GYFLAQYLM → VPVGQEEVC
     243-1104: Missing.

Show »
Length:165
Mass (Da):18,655
Checksum:i1EC4CEA05A33B6B6
GO
Isoform 4 (identifier: Q7Z2W7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MS → MQ
     3-314: Missing.
     675-784: Missing.

Note: No experimental confirmation available.
Show »
Length:682
Mass (Da):79,096
Checksum:iADF16E630E91F0EB
GO

Sequence cautioni

The sequence AAH01135 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAS45276 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti58T → I in AAM10446 (PubMed:11325849).Curated1
Sequence conflicti693W → R in BAB86335 (Ref. 7) Curated1
Sequence conflicti795T → A in AAP92167 (PubMed:16174775).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052383247R → T.Corresponds to variant rs13004520dbSNPEnsembl.1
Natural variantiVAR_052384251Y → C.Corresponds to variant rs17868387dbSNPEnsembl.1
Natural variantiVAR_059837419S → N.Corresponds to variant rs7593557dbSNPEnsembl.1
Natural variantiVAR_052385462M → T.Corresponds to variant rs28902173dbSNPEnsembl.1
Natural variantiVAR_052386732T → I.Corresponds to variant rs17862932dbSNPEnsembl.1
Natural variantiVAR_052387821N → S.Corresponds to variant rs28902201dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0532681 – 188Missing in isoform 2. 2 PublicationsAdd BLAST188
Alternative sequenceiVSP_0123301 – 77Missing in isoform 3. 1 PublicationAdd BLAST77
Alternative sequenceiVSP_0545051 – 2MS → MQ in isoform 4. 1 Publication2
Alternative sequenceiVSP_0545063 – 314Missing in isoform 4. 1 PublicationAdd BLAST312
Alternative sequenceiVSP_012332234 – 242GYFLAQYLM → VPVGQEEVC in isoform 2 and isoform 3. 2 Publications9
Alternative sequenceiVSP_012333243 – 1104Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST862
Alternative sequenceiVSP_054507675 – 784Missing in isoform 4. 1 PublicationAdd BLAST110

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY090109 mRNA. Translation: AAM10446.1.
AY328400 mRNA. Translation: AAP92167.1.
DQ139309 mRNA. Translation: AAZ73614.1.
AY532375 mRNA. Translation: AAS45275.1.
AY532376 mRNA. Translation: AAS45276.1. Different initiation.
AC005538 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71068.1.
BC001135 mRNA. Translation: AAH01135.1. Different initiation.
BC126342 mRNA. Translation: AAI26343.1.
AB061779 mRNA. Translation: BAB86335.1.
CCDSiCCDS33407.1. [Q7Z2W7-1]
RefSeqiNP_076985.4. NM_024080.4. [Q7Z2W7-1]
UniGeneiHs.366053.

Genome annotation databases

EnsembliENST00000324695; ENSP00000323926; ENSG00000144481. [Q7Z2W7-1]
ENST00000409625; ENSP00000386771; ENSG00000144481. [Q7Z2W7-3]
GeneIDi79054.
KEGGihsa:79054.
UCSCiuc002vvi.4. human. [Q7Z2W7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY090109 mRNA. Translation: AAM10446.1.
AY328400 mRNA. Translation: AAP92167.1.
DQ139309 mRNA. Translation: AAZ73614.1.
AY532375 mRNA. Translation: AAS45275.1.
AY532376 mRNA. Translation: AAS45276.1. Different initiation.
AC005538 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71068.1.
BC001135 mRNA. Translation: AAH01135.1. Different initiation.
BC126342 mRNA. Translation: AAI26343.1.
AB061779 mRNA. Translation: BAB86335.1.
CCDSiCCDS33407.1. [Q7Z2W7-1]
RefSeqiNP_076985.4. NM_024080.4. [Q7Z2W7-1]
UniGeneiHs.366053.

3D structure databases

ProteinModelPortaliQ7Z2W7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122512. 11 interactors.
STRINGi9606.ENSP00000323926.

Chemistry databases

BindingDBiQ7Z2W7.
ChEMBLiCHEMBL1075319.
DrugBankiDB00825. Menthol.
GuidetoPHARMACOLOGYi500.

Protein family/group databases

TCDBi1.A.4.5.7. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

iPTMnetiQ7Z2W7.
PhosphoSitePlusiQ7Z2W7.

Polymorphism and mutation databases

BioMutaiTRPM8.
DMDMi143811469.

Proteomic databases

PaxDbiQ7Z2W7.
PRIDEiQ7Z2W7.

Protocols and materials databases

DNASUi79054.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324695; ENSP00000323926; ENSG00000144481. [Q7Z2W7-1]
ENST00000409625; ENSP00000386771; ENSG00000144481. [Q7Z2W7-3]
GeneIDi79054.
KEGGihsa:79054.
UCSCiuc002vvi.4. human. [Q7Z2W7-1]

Organism-specific databases

CTDi79054.
DisGeNETi79054.
GeneCardsiTRPM8.
HGNCiHGNC:17961. TRPM8.
MIMi606678. gene.
neXtProtiNX_Q7Z2W7.
OpenTargetsiENSG00000144481.
PharmGKBiPA38270.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INBX. Eukaryota.
ENOG4110YBY. LUCA.
GeneTreeiENSGT00760000119127.
HOGENOMiHOG000236350.
HOVERGENiHBG100888.
InParanoidiQ7Z2W7.
KOiK04983.
OMAiYIMDDFT.
OrthoDBiEOG091G035A.
PhylomeDBiQ7Z2W7.
TreeFamiTF314204.

Enzyme and pathway databases

ReactomeiR-HSA-3295583. TRP channels.

Miscellaneous databases

GeneWikiiTRPM8.
GenomeRNAii79054.
PROiQ7Z2W7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144481.
CleanExiHS_TRPM8.
ExpressionAtlasiQ7Z2W7. baseline and differential.
GenevisibleiQ7Z2W7. HS.

Family and domain databases

InterProiIPR005821. Ion_trans_dom.
IPR029603. TRPM8.
[Graphical view]
PANTHERiPTHR13800:SF9. PTHR13800:SF9. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRPM8_HUMAN
AccessioniPrimary (citable) accession number: Q7Z2W7
Secondary accession number(s): A0AVG2
, Q3YFM7, Q6QNH9, Q8TAC3, Q8TDX8, Q9BVK1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: April 3, 2007
Last modified: November 2, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The sensation of coolness triggered by eucalyptol or menthol may be explained by the fact that menthol and cool temperatures sensations are detected by this protein.
Its expression in most prostate tumors as well as the presence of an immunogenic epitope suggest that it may be suitable for the design of peptide vaccination strategies for prostate cancers.

Caution

The 192-residue sequence submitted as AAS45276 has been confirmed by the authors of PubMed:22128173 to be incorrect as translation starts from a downstream methionine.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.