Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TRPM8 (Q7Z2W7) - Overview - Molecular Target Synopsis

Protein


TRPM8, Transient receptor potential cation channel subfamily M member 8
UniProt Q7Z2W7

Also Known as TRPM8_HUMAN, TRPM8, LTRPC6, TRPP8

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. 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).

Isoforms / Transcripts (Protein Coding)


Drugs


TRPM8 is targeted by Approved Drug Menthol. (see details)
Menthol

Sub-cellular localization


UniProt: TRPM8 is active in the following subcellular-locations: cell membrane, endoplasmic reticulum membrane, membrane raft.
GO terms: TRPM8 is active in the following subcellular-locations: endoplasmic reticulum membrane, external side of plasma membrane, integral component of membrane, membrane raft, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TRPM8 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 1005 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: UACC_62, SR, MDA_N

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: DMS 53, G-402, NCI-H1092

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


At greater than 75% identity similarity to TRPM8 there are:
4 structures (16 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TRPM8 has been screened with 698 compounds (837 bioactivities), 422 compounds have bioactivities that show binding affinity of <= 500nM (443 bioactivities). (see details)