Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''TRPM2''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Structure

The protein encoded by this gene is a non-selective calcium-permeable

cation channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

and is part of the

Transient Receptor Potential Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TR ...

ion channel super family. The closest relative is the cold and menthol activated

TRPM8 Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular ...

ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular

ADP-ribose Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ...

in synergy with free intracellular

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as d ...

. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Function

The ''TRPM2'' gene is highly expressed in the brain and was implicated by both genetic linkage studies in families and then by case control or trio allelic association studies in the genetic aetiology of

bipolar affective disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

(Manic Depression). The physiological role of TRPM2 is not well understood. It was shown to be involved in insulin secretion. In the

immune cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

it mediates parts of the responses to

TNF-alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

. A role has been suggested for TRPM2 in activation of

NLRP3 NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1. NLRP3 is ...

inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes. In the brain it is involved in the toxicity of amyloid beta, a protein associated with Alzheimer's disease. In 2016, TRPM2 channel was strongly implicated in the detection of non-painful warm stimuli. Chun-Hsiang Tan and Peter McNaughton studied the responses of actual sensory neurons to thermal stimuli, then used an RNA-sequencing strategy to identify TRPM2 as genetically required for warmth detection in the non-noxious range of 33–38 °C.

Clinical significance

TRPM2 expression and function help preserve cancer cell viability. TRPM2 channels are highly expressed in many cancers, notably

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in th ...

References

External links

* {{Transient receptor potential channel modulators Ion channels Biology of bipolar disorder Nudix hydrolases

Structure

Function

Clinical significance

See also

References

Further reading

External links