TRPM2
TRPM2 forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. TRPM2 is activated by oxidative stress and confers susceptibility to cell death.
Function
Isoform 1
Nonselective, voltage-independent cation channel that mediates Na+ and Ca2+ influx, leading to increased cytoplasmic Ca2+ levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:25620041, PubMed:27383051, PubMed:27068538, PubMed:28775320, PubMed:29745897, PubMed:30467180).
Functions as ligand-gated ion channel (PubMed:19171771, PubMed:25620041, PubMed:28775320, PubMed:30467180).
Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca2+ binding to trigger channel opening (PubMed:19171771, PubMed:25620041, PubMed:28775320, PubMed:29745897, PubMed:30467180).
Extracellular calcium passes through the channel and increases channel activity (PubMed:19171771).
Contributes to Ca2+ release from intracellular stores in response to ADP-ribose (PubMed:19454650).
Plays a role in numerous processes that involve signaling via intracellular Ca2+ levels (Probable). Besides, mediates the release of lysosomal Zn2+ stores in response to reactive oxygen species, leading to increased cytosolic Zn2+ levels (PubMed:25562606, PubMed:27068538).
Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673).
Activated by intracellular ADP-ribose, beta-NAD (NAD+) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:25620041, PubMed:27383051, PubMed:27068538, PubMed:30467180).
The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360).
Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673).
Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272).
Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca2+ levels (By similarity).
Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca2+ levels (By similarity).
Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca2+ and Zn2+ levels (PubMed:27068538).
Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606).
Isoform 2
Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose.
Isoform 3
Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress.
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Datasheet