General Information of Target

Target ID LDTP08019
Target Name Transient receptor potential cation channel subfamily M member 8 (TRPM8)
Gene Name TRPM8
Gene ID 79054
Synonyms
LTRPC6; TRPP8; Transient receptor potential cation channel subfamily M member 8; Long transient receptor potential channel 6; LTrpC-6; LTrpC6; Transient receptor potential p8; Trp-p8
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSFRAARLSMRNRRNDTLDSTRTLYSSASRSTDLSYSESDLVNFIQANFKKRECVFFTKD
SKATENVCKCGYAQSQHMEGTQINQSEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYIRL
SCDTDAEILYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWIL
TGGTHYGLMKYIGEVVRDNTISRSSEENIVAIGIAAWGMVSNRDTLIRNCDAEGYFLAQY
LMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTIQDSNYGGKIP
IVCFAQGGGKETLKAINTSIKNKIPCVVVEGSGQIADVIASLVEVEDALTSSAVKEKLVR
FLPRTVSRLPEEETESWIKWLKEILECSHLLTVIKMEEAGDEIVSNAISYALYKAFSTSE
QDKDNWNGQLKLLLEWNQLDLANDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLEN
GLNLRKFLTHDVLTELFSNHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRGFRKEDR
NGRDEMDIELHDVSPITRHPLQALFIWAILQNKKELSKVIWEQTRGCTLAALGASKLLKT
LAKVKNDINAAGESEELANEYETRAVELFTECYSSDEDLAEQLLVYSCEAWGGSNCLELA
VEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGFVSFRKKPVDKH
KKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHPPELVLYSLVFVLFC
DEVRQWYVNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFT
LRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIF
RSVIYEPYLAMFGQVPSDVDGTTYDFAHCTFTGNESKPLCVELDEHNLPRFPEWITIPLV
CIYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQRYFLVQEYCSRLNIPFPFIVFAY
FYMVVKKCFKCCCKEKNMESSVCCFKNEDNETLAWEGVMKENYLVKINTKANDTSEEMRH
RFRQLDTKLNDLKGLLKEIANKIK
Target Type
Successful
Target Bioclass
Transporter and channel
Family
Transient receptor (TC 1.A.4) family, LTrpC subfamily, TRPM8 sub-subfamily
Subcellular location
Cell membrane
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 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. Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.
TTD ID
T41955
Uniprot ID
Q7Z2W7
DrugMap ID
TTXDKTO
Ensemble ID
ENST00000324695.9
HGNC ID
HGNC:17961
ChEMBL ID
CHEMBL1075319

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CAL148 SNV: p.E386K .
CAL62 SNV: p.P958T .
DU145 SNV: p.E53Ter .
HCC1419 SNV: p.V1065I .
HEC1 Deletion: p.L132RfsTer2 .
HEC1B Deletion: p.L132RfsTer2 .
HUCCT1 Deletion: p.E1004GfsTer22 .
JURKAT SNV: p.R160H .
LN229 SNV: p.I290V .
MEWO SNV: p.N279S
Substitution: p.P1012L
.
NCIH1048 SNV: p.V867M .
NCIH2172 SNV: p.N12Y .
NCIH2286 SNV: p.A884S .
NCIH2291 SNV: p.F730L .
NCIH23 SNV: p.L412V .
OZ Substitution: p.E194Ter .
SUPT1 SNV: p.G150R .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info 
K719(3.51)  LDD0277  [1]

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270