Reviewed, UniProtKB/Swiss-Prot Q7Z2W7 (TRPM8_HUMAN)

Names and origin

Protein names

Recommended name:
    Transient receptor potential cation channel subfamily M member 8
Alternative name(s):
    Long transient receptor potential channel 6
      Short name(s)=LTrpC6
    Transient receptor potential-p8
      Short name(s)=Trp-p8

Gene names

Name:	TRPM8
Synonyms:	LTRPC6, TRPP8

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1104 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript 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.
Subcellular location	Membrane; Multi-pass membrane proteinProbable.
Tissue specificity	Expressed in prostate. Also expressed in most in prostate tumors. Also expressed in non-prostatic primary tumors such as colon, lung, breast and skin tumors.
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.
Sequence similarities	Belongs to the transient receptor family. LTrpC subfamily.

Ontologies

Keywords
Biological process	Ion transport Sensory transduction Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Molecular function	Ionic channel
Gene Ontology (GO)
None. [Check GOA]

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z2W7-1)

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.

Isoform 2 (identifier: Q7Z2W7-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: MSFRAARLSM...VFFTKDSKAT → MKSFLPVHTIVLIR
     234-242: GYFLAQYLM → VPVGQEEVC
     243-1104: Missing.

Isoform 3 (identifier: Q7Z2W7-3)

Also known as: Alpha;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 1104	1104	Transient receptor potential cation channel subfamily M member 8
Regions
	Topological domain	1 – 691	691	Cytoplasmic Potential
	Transmembrane	692 – 712	21	1 Potential
	Topological domain	713 – 734	22	Extracellular Potential
	Transmembrane	735 – 755	21	2 Potential
	Topological domain	756 – 759	4	Cytoplasmic Potential
	Transmembrane	760 – 780	21	3 Potential
	Topological domain	781 – 794	14	Extracellular Potential
	Transmembrane	795 – 815	21	4 Potential
	Topological domain	816 – 829	14	Cytoplasmic Potential
	Transmembrane	830 – 850	21	5 Potential
	Topological domain	851 – 958	108	Extracellular Potential
	Transmembrane	959 – 979	21	6 Potential
	Topological domain	980 – 1104	125	Cytoplasmic Potential
	Region	187 – 195	9	Epitope; activates specific cytotoxic T lymphocytes
Natural variations
	Alternative sequence	1 – 77	77	Missing in isoform 3.
	Alternative sequence	1 – 64	64	MSFRA…DSKAT → MKSFLPVHTIVLIR in isoform 2.
	Alternative sequence	234 – 242	9	GYFLAQYLM → VPVGQEEVC in isoform 2 and isoform 3.
	Alternative sequence	243 – 1104	862	Missing in isoform 2 and isoform 3.
Experimental info
	Sequence conflict	58	1	T → I in AAM10446. Ref.1
	Sequence conflict	693	1	W → R in BAB86335. Ref.5
	Sequence conflict	795	1	T → A in AAP92167. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 5D88F5081EDFA632	FASTA	1,104	127,685
	10 20 30 40 50 60 MSFRAARLSM RNRRNDTLDS TRTLYSSASR STDLSYSESD LVNFIQANFK KRECVFFTKD 70 80 90 100 110 120 SKATENVCKC GYAQSQHMEG TQINQSEKWN YKKHTKEFPT DAFGDIQFET LGKKGKYIRL 130 140 150 160 170 180 SCDTDAEILY ELLTQHWHLK TPNLVISVTG GAKNFALKPR MRKIFSRLIY IAQSKGAWIL 190 200 210 220 230 240 TGGTHYGLMK YIGEVVRDNT ISRSSEENIV AIGIAAWGMV SNRDTLIRNC DAEGYFLAQY 250 260 270 280 290 300 LMDDFTRDPL YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTI QDSNYGGKIP 310 320 330 340 350 360 IVCFAQGGGK ETLKAINTSI KNKIPCVVVE GSGQIADVIA SLVEVEDALT SSAVKEKLVR 370 380 390 400 410 420 FLPRTVSRLP EEETESWIKW LKEILECSHL LTVIKMEEAG DEIVSNAISY ALYKAFSTSE 430 440 450 460 470 480 QDKDNWNGQL KLLLEWNQLD LANDEIFTND RRWESADLQE VMFTALIKDR PKFVRLFLEN 490 500 510 520 530 540 GLNLRKFLTH DVLTELFSNH FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRGFRKEDR 550 560 570 580 590 600 NGRDEMDIEL HDVSPITRHP LQALFIWAIL QNKKELSKVI WEQTRGCTLA ALGASKLLKT 610 620 630 640 650 660 LAKVKNDINA AGESEELANE YETRAVELFT ECYSSDEDLA EQLLVYSCEA WGGSNCLELA 670 680 690 700 710 720 VEATDQHFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF IIPLVGCGFV SFRKKPVDKH 730 740 750 760 770 780 KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL LFAYVLLMDF HSVPHPPELV LYSLVFVLFC 790 800 810 820 830 840 DEVRQWYVNG 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 GTTYDFAHCT FTGNESKPLC VELDEHNLPR FPEWITIPLV 970 980 990 1000 1010 1020 CIYMLSTNIL LVNLLVAMFG YTVGTVQENN DQVWKFQRYF LVQEYCSRLN IPFPFIVFAY 1030 1040 1050 1060 1070 1080 FYMVVKKCFK CCCKEKNMES SVCCFKNEDN ETLAWEGVMK ENYLVKINTK ANDTSEEMRH 1090 1100 RFRQLDTKLN DLKGLLKEIA NKIK
	Isoform 2 (Beta) [UniParc]. Checksum: 497E80248CF1D45C		192	21,740
	10 20 30 40 50 60 MKSFLPVHTI VLIRENVCKC GYAQSQHMEG TQINQSEKWN YKKHTKEFPT DAFGDIQFET 70 80 90 100 110 120 LGKKGKYIRL SCDTDAEILY ELLTQHWHLK TPNLVISVTG GAKNFALKPR MRKIFSRLIY 130 140 150 160 170 180 IAQSKGAWIL TGGTHYGLMK YIGEVVRDNT ISRSSEENIV AIGIAAWGMV SNRDTLIRNC 190 DAEVPVGQEE VC
	Isoform 3 (Alpha) [UniParc]. Checksum: 1EC4CEA05A33B6B6		165	18,655
	10 20 30 40 50 60 MEGTQINQSE KWNYKKHTKE FPTDAFGDIQ FETLGKKGKY IRLSCDTDAE ILYELLTQHW 70 80 90 100 110 120 HLKTPNLVIS VTGGAKNFAL KPRMRKIFSR LIYIAQSKGA WILTGGTHYG LMKYIGEVVR 130 140 150 160 DNTISRSSEE NIVAIGIAAW GMVSNRDTLI RNCDAEVPVG QEEVC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins." Tsavaler L., Shapero M.H., Morkowski S., Laus R. Cancer Res. 61:3760-3769(2001) [PubMed: 11325849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Prostate.
[2]	"Characterization of heterologous expressed human TRPM8 channel in HEK293 cells." Bidaux G., Vanden Abeele F., Rebrikov D., Panchin Y., Roudbaraki M., Prevarskaya N. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Prostate.
[3]	"Characterization of short TRPM8 splice beta from prostate cancer cell line LNCaP." Bidaux G., Roudbaraki M., Gauthier J., Prevarskaya N. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Skin.
[5]	"Molecular cloning of a novel member of LTRP channel family, LTRPC6." Sano Y., Inamura K., Miyake A., Mochizuki S., Yokoi H., Kitada C., Nozawa K., Matsushime H., Furuichi K. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-1104 (ISOFORM 1).
[6]	"Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein trp-p8." Kiessling A., Fuessel S., Schmitz M., Stevanovic S., Meye A., Weigle B., Klenk U., Wirth M.P., Rieber E.P. Prostate 56:270-279(2003) [PubMed: 12858355] [Abstract] Cited for: TISSUE SPECIFICITY, EPITOPE MAPPING.
[7]	"The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels." Voets T., Droogmans G., Wissenbach U., Janssens A., Flockerzi V., Nilius B. Nature 430:748-754(2004) [PubMed: 15306801] [Abstract] Cited for: FUNCTION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY090109 mRNA. Translation: AAM10446.1. AY328400 mRNA. Translation: AAP92167.1. AY532375 mRNA. Translation: AAS45275.1. AY532376 mRNA. Translation: AAS45276.1. BC001135 mRNA. Translation: AAH01135.1. AB061779 mRNA. Translation: BAB86335.1.
RefSeq	NP_076985.4.
UniGene	Hs.366053
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000144481. Homo sapiens. [Contig view]
GeneID	79054.
KEGG	hsa:79054.
NMPDR	fig|9606.3.peg.19549.
Organism-specific databases
H-InvDB	HIX0002939.
HGNC	HGNC:17961. TRPM8.
MIM	606678. gene.
PharmGKB	PA38270.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOGENOM	Q7Z2W7.
HOVERGEN	Q7Z2W7.
Gene expression databases
ArrayExpress	Q7Z2W7.
CleanEx	HS_TRPM8.
GermOnline	ENSG00000144481. Homo sapiens.
Family and domain databases
InterPro	IPR005821. Ion_trans. [Graphical view]
Pfam	PF00520. Ion_trans. 1 hit. [Graphical view]
ProDom	Q7Z2W7. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
DrugBank	DB00825. Menthol.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

TRPM8_HUMAN

Accession

Primary (citable) accession number: Q7Z2W7
Secondary accession number(s): Q6QNH9 , Q8TAC3, Q8TDX8, Q9BVK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 21, 2004
Last sequence update:	April 3, 2007
Last modified:	July 22, 2008
This is version 45 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)