Transient receptor potential cation channel subfamily M member 8

NameTransient receptor potential cation channel subfamily M member 8
Synonyms
  • Long transient receptor potential channel 6
  • LTrpC-6
  • LTRPC6
  • Transient receptor potential p8
  • Trp-p8
  • TRPP8
Gene NameTRPM8
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002359|Transient receptor potential cation channel subfamily M member 8
MSFRAARLSMRNRRNDTLDSTRTLYSSASRSTDLSYSESDLVNFIQANFKKRECVFFTKD
SKATENVCKCGYAQSQHMEGTQINQSEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYIRL
SCDTDAEILYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWIL
TGGTHYGLMKYIGEVVRDNTISRSSEENIVAIGIAAWGMVSNRDTLIRNCDAEGYFLAQY
LMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTIQDSNYGGKIP
IVCFAQGGGKETLKAINTSIKNKIPCVVVEGSGQIADVIASLVEVEDALTSSAVKEKLVR
FLPRTVSRLPEEETESWIKWLKEILECSHLLTVIKMEEAGDEIVSNAISYALYKAFSTSE
QDKDNWNGQLKLLLEWNQLDLANDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLEN
GLNLRKFLTHDVLTELFSNHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRGFRKEDR
NGRDEMDIELHDVSPITRHPLQALFIWAILQNKKELSKVIWEQTRGCTLAALGASKLLKT
LAKVKNDINAAGESEELANEYETRAVELFTECYSSDEDLAEQLLVYSCEAWGGSNCLELA
VEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGFVSFRKKPVDKH
KKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHPPELVLYSLVFVLFC
DEVRQWYVNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFT
LRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIF
RSVIYEPYLAMFGQVPSDVDGTTYDFAHCTFTGNESKPLCVELDEHNLPRFPEWITIPLV
CIYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQRYFLVQEYCSRLNIPFPFIVFAY
FYMVVKKCFKCCCKEKNMESSVCCFKNEDNETLAWEGVMKENYLVKINTKANDTSEEMRH
RFRQLDTKLNDLKGLLKEIANKIK
Number of residues1104
Molecular Weight127684.035
Theoretical pI7.25
GO Classification
Functions
  • calcium channel activity
Processes
  • transmembrane transport
  • ion transmembrane transport
  • protein homotetramerization
  • calcium ion transmembrane transport
  • cellular calcium ion homeostasis
  • protein homotrimerization
  • response to cold
  • detection of temperature stimulus
  • thermoception
Components
  • plasma membrane
  • endoplasmic reticulum membrane
  • integral component of membrane
  • external side of plasma membrane
  • membrane raft
General FunctionCalcium channel activity
Specific FunctionReceptor-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.
Pfam Domain Function
Transmembrane Regions692-712 735-755 760-780 795-815 830-850 959-979
GenBank Protein ID20147036
UniProtKB IDQ7Z2W7
UniProtKB Entry NameTRPM8_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0019077|Transient receptor potential cation channel subfamily M member 8 (TRPM8)
ATGTCCTTTCGGGCAGCCAGGCTCAGCATGAGGAACAGAAGGAATGACACTCTGGACAGC
ACCCGGACCCTGTACTCCAGCGCGTCTCGGAGCACAGACTTGTCTTACAGTGAAAGCGAC
TTGGTGAATTTTATTCAAGCAAATTTTAAGAAACGAGAATGTGTCTTCTTTACCAAAGAT
TCCAAGGCCACGGAGAATGTGTGCAAGTGTGGCTATGCCCAGAGCCAGCACATGGAAGGC
ACCCAGATCAACCAAAGTGAGAAATGGAACTACAAGAAACACACCAAGGAATTTCCTACC
GACGCCTTTGGGGATATTCAGTTTGAGACACTGGGGAAGAAAGGGAAGTATATACGTCTG
TCCTGCGACACGGACGCGGAAATCCTTTACGAGCTGCTGACCCAGCACTGGCACCTGAAA
ACACCCAACCTGGTCATTTCTGTGACCGGGGGCGCCAAGAACTTCGCCCTGAAGCCGCGC
ATGCGCAAGATCTTCAGCCGGCTCATCTACATCGCGCAGTCCAAAGGTGCTTGGATTCTC
ACGGGAGGCACCCATTATGGCCTGATGAAGTACATCGGGGAGGTGGTGAGAGATAACACC
ATCAGCAGGAGTTCAGAGGAGAATATTGTGGCCATTGGCATAGCAGCTTGGGGCATGGTC
TCCAACCGGGACACCCTCATCAGGAATTGCGATGCTGAGGGCTATTTTTTAGCCCAGTAC
CTTATGGATGACTTCACAAGAGATCCACTGTATATCCTGGACAACAACCACACACATTTG
CTGCTCGTGGACAATGGCTGTCATGGACATCCCACTGTCGAAGCAAAGCTCCGGAATCAG
CTAGAGAAGTATATCTCTGAGCGCACTATTCAAGATTCCAACTATGGTGGCAAGATCCCC
ATTGTGTGTTTTGCCCAAGGAGGTGGAAAAGAGACTTTGAAAGCCATCAATACCTCCATC
AAAAATAAAATTCCTTGTGTGGTGGTGGAAGGCTCGGGCCAGATCGCTGATGTGATCGCT
AGCCTGGTGGAGGTGGAGGATGCCCTGACATCTTCTGCCGTCAAGGAGAAGCTGGTGCGC
TTTTTACCCCGCACGGTGTCCCGGCTGCCTGAGGAGGAGACTGAGAGTTGGATCAAATGG
CTCAAAGAAATTCTCGAATGTTCTCACCTATTAACAGTTATTAAAATGGAAGAAGCTGGG
GATGAAATTGTGAGCAATGCCATCTCCTACGCTCTATACAAAGCCTTCAGCACCAGTGAG
CAAGACAAGGATAACTGGAATGGGCAGCTGAAGCTTCTGCTGGAGTGGAACCAGCTGGAC
TTAGCCAATGATGAGATTTTCACCAATGACCGCCGATGGGAGTCTGCTGACCTTCAAGAA
GTCATGTTTACGGCTCTCATAAAGGACAGACCCAAGTTTGTCCGCCTCTTTCTGGAGAAT
GGCTTGAACCTACGGAAGTTTCTCACCCATGATGTCCTCACTGAACTCTTCTCCAACCAC
TTCAGCACGCTTGTGTACCGGAATCTGCAGATCGCCAAGAATTCCTATAATGATGCCCTC
CTCACGTTTGTCTGGAAACTGGTTGCGAACTTCCGAAGAGGCTTCCGGAAGGAAGACAGA
AATGGCCGGGACGAGATGGACATAGAACTCCACGACGTGTCTCCTATTACTCGGCACCCC
CTGCAAGCTCTCTTCATCTGGGCCATTCTTCAGAATAAGAAGGAACTCTCCAAAGTCATT
TGGGAGCAGACCAGGGGCTGCACTCTGGCAGCCCTGGGAGCCAGCAAGCTTCTGAAGACT
CTGGCCAAAGTGAAGAACGACATCAATGCTGCTGGGGAGTCCGAGGAGCTGGCTAATGAG
TACGAGACCCGGGCTGTTGAGCTGTTCACTGAGTGTTACAGCAGCGATGAAGACTTGGCA
GAACAGCTGCTGGTCTATTCCTGTGAAGCTTGGGGTGGAAGCAACTGTCTGGAGCTGGCG
GTGGAGGCCACAGACCAGCATTTCATCGCCCAGCCTGGGGTCCAGAATTTTCTTTCTAAG
CAATGGTATGGAGAGATTTCCCGAGACACCAAGAACTGGAAGATTATCCTGTGTCTGTTT
ATTATACCCTTGGTGGGCTGTGGCTTTGTATCATTTAGGAAGAAACCTGTCGACAAGCAC
AAGAAGCTGCTTTGGTACTATGTGGCGTTCTTCACCTCCCCCTTCGTGGTCTTCTCCTGG
AATGTGGTCTTCTACATCGCCTTCCTCCTGCTGTTTGCCTACGTGCTGCTCATGGATTTC
CATTCGGTGCCACACCCCCCCGAGCTGGTCCTGTACTCGCTGGTCTTTGTCCTCTTCTGT
GATGAAGTGAGACAGTGGTACGTAAATGGGGTGAATTATTTTACTGACCTGTGGAATGTG
ATGGACACGCTGGGGCTTTTTTACTTCATAGCAGGAATTGTATTTCGGCTCCACTCTTCT
AATAAAAGCTCTTTGTATTCTGGACGAGTCATTTTCTGTCTGGACTACATTATTTTCACT
CTAAGATTGATCCACATTTTTACTGTAAGCAGAAACTTAGGACCCAAGATTATAATGCTG
CAGAGGATGCTGATCGATGTGTTCTTCTTCCTGTTCCTCTTTGCGGTGTGGATGGTGGCC
TTTGGCGTGGCCAGGCAAGGGATCCTTAGGCAGAATGAGCAGCGCTGGAGGTGGATATTC
CGTTCGGTCATCTACGAGCCCTACCTGGCCATGTTCGGCCAGGTGCCCAGTGACGTGGAT
GGTACCACGTATGACTTTGCCCACTGCACCTTCACTGGGAATGAGTCCAAGCCACTGTGT
GTGGAGCTGGATGAGCACAACCTGCCCCGGTTCCCCGAGTGGATCACCATCCCCCTGGTG
TGCATCTACATGTTATCCACCAACATCCTGCTGGTCAACCTGCTGGTCGCCATGTTTGGC
TACACGGTGGGCACCGTCCAGGAGAACAATGACCAGGTCTGGAAGTTCCAGAGGTACTTC
CTGGTGCAGGAGTACTGCAGCCGCCTCAATATCCCCTTCCCCTTCATCGTCTTCGCTTAC
TTCTACATGGTGGTGAAGAAGTGCTTCAAGTGTTGCTGCAAGGAGAAAAACATGGAGTCT
TCTGTCTGCTGTTTCAAAAATGAAGACAATGAGACTCTGGCATGGGAGGGTGTCATGAAG
GAAAACTACCTTGTCAAGATCAACACAAAAGCCAACGACACCTCAGAGGAAATGAGGCAT
CGATTTAGACAACTGGATACAAAGCTTAATGATCTCAAGGGTCTTCTGAAAGAGATTGCT
AATAAAATCAAATAA
GenBank Gene IDAY090109
GeneCard IDNot Available
GenAtlas IDTRPM8
HGNC IDHGNC:17961
Chromosome Location2
Locus2q37.1
References
  1. Tsavaler L, Shapero MH, Morkowski S, Laus R: 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. Cancer Res. 2001 May 1;61(9):3760-9. 11325849
  2. Thebault S, Lemonnier L, Bidaux G, Flourakis M, Bavencoffe A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y, Skryma R, Prevarskaya N: Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biol Chem. 2005 Nov 25;280(47):39423-35. Epub 2005 Sep 20. 16174775
  3. Bidaux G, Beck B, Zholos A, Gordienko D, Lemonnier L, Flourakis M, Roudbaraki M, Borowiec AS, Fernandez J, Delcourt P, Lepage G, Shuba Y, Skryma R, Prevarskaya N: Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms. J Biol Chem. 2012 Jan 27;287(5):2948-62. doi: 10.1074/jbc.M111.270256. Epub 2011 Nov 28. 22128173
  4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. Kiessling A, Fussel S, Schmitz M, Stevanovic S, Meye A, Weigle B, Klenk U, Wirth MP, Rieber EP: Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein trp-p8. Prostate. 2003 Sep 1;56(4):270-9. 12858355
  7. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B: The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature. 2004 Aug 12;430(7001):748-54. 15306801
  8. Erler I, Al-Ansary DM, Wissenbach U, Wagner TF, Flockerzi V, Niemeyer BA: Trafficking and assembly of the cold-sensitive TRPM8 channel. J Biol Chem. 2006 Dec 15;281(50):38396-404. Epub 2006 Oct 25. 17065148
  9. Gkika D, Lemonnier L, Shapovalov G, Gordienko D, Poux C, Bernardini M, Bokhobza A, Bidaux G, Degerny C, Verreman K, Guarmit B, Benahmed M, de Launoit Y, Bindels RJ, Fiorio Pla A, Prevarskaya N: TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity. J Cell Biol. 2015 Jan 5;208(1):89-107. doi: 10.1083/jcb.201402076. 25559186