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.

Transient Receptor Potential Cation Channel Subfamily M Member 2

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.

Biological Process calcium ion import across plasma membrane Source:UniProtKB
Biological Process calcium ion transmembrane import into cytosol Source:UniProtKB2 Publications
Biological Process calcium ion transmembrane transport Source:UniProtKB5 Publications
Biological Process calcium ion transport Source:ProtInc1 Publication
Biological Process calcium-mediated signaling using intracellular calcium Source Source:UniProtKB
Biological Process cation transmembrane transport Source:GO_Central1 Publication
Biological Process cellular response to calcium ion Source:UniProtKB1 Publication
Biological Process cellular response to hydrogen peroxide Source:UniProtKB1 Publication
Biological Process cellular response to purine-containing compound Source:UniProtKB
Biological Process cellular response to temperature stimulus Source:UniProtKB
Biological Process dendritic cell chemotaxis Source:UniProtKB
Biological Process dendritic cell differentiation Source:UniProtKB
Biological Process estrous cycle Source:Ensembl
Biological Process positive regulation of insulin secretion Source:Ensembl
Biological Process positive regulation of oxidative stress-induced neuron death Source:Ensembl
Biological Process protein homotetramerization Source:UniProtKB1 Publication
Biological Process regulation of actin cytoskeleton reorganization Source:UniProtKB1 Publication
Biological Process regulation of filopodium assembly Source:UniProtKB1 Publication
Biological Process release of sequestered calcium ion into cytosol Source:UniProtKB1 Publication
Biological Process response to heat Source:Ensembl
Biological Process response to hydroperoxide Source:Ensembl
Biological Process response to purine-containing compound Source:UniProtKB1 Publication
Biological Process temperature homeostasis Source:UniProtKB
Biological Process zinc ion transmembrane transport Source:UniProtKB1 Publication

Cell membrane
Perikaryon
Cell projection
Cytoplasmic vesicle
Lysosome
Detected at the cell membrane and in intracellular vesicles in cortical neurons. Detected on neuronal cell bodies and neurites (By similarity).
Detected on the cell membrane in polymorphonuclear neutrophils. Detected on cytoplasmic vesicles and lysosomes in immature bone marrow dendritic cells (By similarity).
Isoform 1
Cell membrane
Isoform 2
Cell membrane
Isoform 3
Cell membrane

Cytoplasmic: 1-752
Helical: 753-769
Cytoplasmic: 770-795
Helical: 796-816
Extracellular: 817-827
Helical: 828-848
Cytoplasmic: 849-867
Helical: 868-888
Extracellular: 889-896
Helical: 897-917
Cytoplasmic: 918-929
Helical: 930-950
Extracellular: 951-970
Helical: 897-917
Cytoplasmic: 918-929
Helical: 930-950
Extracellular: 951-970
Pore-forming: 971-985
Extracellular: 986-1022
Helical: 1023-1044
Cytoplasmic: 1045-1079
Helical: 1080-1098
Cytoplasmic: 1099-1503