TRPM2

Description

The TRPM2 (transient receptor potential cation channel subfamily M member 2) is a protein-coding gene located on chromosome 21.

Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

== Structure == The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the Transient Receptor Potential ion channel super family. The closest relative is the cold and menthol activated TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to cell death. 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 (Manic Depression). The physiological role of TRPM2 is not well understood. It was shown to be involved in insulin secretion.

[Isoform 1]: This isoform acts as a nonselective, voltage-independent cation channel that allows sodium (Na+) and calcium (Ca2+) ions to enter the cell. This influx increases the calcium levels inside the cell. It functions as a ligand-gated ion channel, meaning it opens when specific molecules bind to it. ADP-ribose binds to the Nudix domain in the cytoplasm, causing the channel to change shape. This priming step requires additional binding of calcium ions to trigger channel opening. Calcium ions from outside the cell can pass through the channel, further increasing its activity. This isoform contributes to the release of calcium from intracellular stores in response to ADP-ribose. It plays a key role in various cellular processes involving intracellular calcium signaling. It also facilitates the release of zinc (Zn2+) ions from lysosomes in response to reactive oxygen species, increasing zinc levels in the cell's cytoplasm. This isoform is activated by moderate heat (35 to 40 degrees Celsius), intracellular ADP-ribose, beta-NAD (NAD+), and similar compounds. It can also be activated by oxidative stress caused by reactive oxygen or nitrogen species. The precise physiological activators are still under investigation, with ADP-ribose and ADP-ribose-2'-phosphate considered potential candidates. Activation by ADP-ribose and beta-NAD is strongly enhanced by moderate heat. Reactive oxygen species lower the threshold for activation by moderate heat. This isoform contributes to behavioral and physiological responses to moderate heat, helping regulate body temperature. It plays a role in insulin secretion, which requires elevated cytoplasmic calcium levels. It is essential for normal interferon-gamma (IFNG) and cytokine secretion, as well as innate immune responses to bacterial infections. It is needed for normal phagocytosis and cytokine release by macrophages exposed to zymosan (a yeast cell wall component) in laboratory settings. This isoform is involved in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis (directed movement) through its role in regulating cytoplasmic calcium levels. It plays a role in regulating the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species by increasing cytoplasmic calcium and zinc levels. It makes cells more susceptible to death following oxidative stress.

TRPM2 is also known as EREG1, KNP3, LTRPC2, LTrpC-2, NUDT9H, NUDT9L1, TRPC7.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing