TRPM2
entrez
7226
canonical
uniprot
O94759
canonical
ensembl
ENSG00000142185
resolver
ensp
ENSP00000300481
resolver
ensp
ENSP00000300482
resolver
ensp
ENSP00000381023
resolver
ensp
ENSP00000381026
resolver
ensp
ENSP00000573516
resolver
enst
ENST00000397932
resolver
genesymbol
TRPM2
resolver
genesymbol_syn
EREG1
resolver
genesymbol_syn
KNP3
resolver
genesymbol_syn
LTRPC2
resolver
genesymbol_syn
TRPC7
resolver
hgnc
HGNC:12339
resolver
uniprot
B4DVI8
resolver
uniprot
D3DSL6
resolver
uniprot
E9PGK7
resolver
uniprot
Q14DR2
resolver
uniprot
Q5KTC2
resolver
uniprot
Q6J3P5
resolver
uniprot
Q96KN6
resolver
uniprot
Q96Q93
resolver
uniprot_entry
B4DVI8_HUMAN
resolver
uniprot_entry
E9PGK7_HUMAN
resolver
uniprot_entry
Q14DR2_HUMAN
resolver
uniprot_entry
TRPM2_HUMAN
resolver
uniprot_sec
D3DSL6
resolver
uniprot_sec
Q5KTC2
resolver
uniprot_sec
Q6J3P5
resolver
uniprot_sec
Q96KN6
resolver
uniprot_sec
Q96Q93
resolver
activity_regulation
ACTIVITY REGULATION: Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:11960981, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:25620041, PubMed:27068538, PubMed:27383051, PubMed:30467180). Ca(2+) and PI(4,5)P2 are required for channel opening by ADP-ribose (PubMed:11385575, PubMed:33924946). 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). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Inactivated by exposure to extracellular pH between 4.0 and 6.5; irreversibly inactivated when open channels are exposed to extracellular pH between 4.0 and 6.5, while pre-exposure of closed channels to extracellular pH 5.5 gives rise to currents that rapidly inactivate, but protects against irreversible inactivation (PubMed:20660597). Inactivated by intracellular ATP (PubMed:11509734). Activated by arachidonic acid (PubMed:11804595). Inhibited by 2-aminoethyl diphenylborinate (2-APB) (PubMed:28775320). {ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:15561722, ECO:0000269|PubMed:20660597, ECO:0000269|PubMed:25620041, ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051, ECO:0000269|PubMed:28775320, ECO:0000269|PubMed:30467180, ECO:0000269|PubMed:33924946}.
uniprot
proteins
amino_acid_sequence
MEPSALRKAGSEQEEGFEGLPRRVTDLGMVSNLRRSNSSLFKSWRLQCPFGNNDKQESLSSWIPENIKKKECVYFVESSKLSDAGKVVCQCGYTHEQHLEEATKPHTFQGTQWDPKKHVQEMPTDAFGDIVFTGLSQKVKKYVRVSQDTPSSVIYHLMTQHWGLDVPNLLISVTGGAKNFNMKPRLKSIFRRGLVKVAQTTGAWIITGGSHTGVMKQVGEAVRDFSLSSSYKEGELITIGVATWGTVHRREGLIHPTGSFPAEYILDEDGQGNLTCLDSNHSHFILVDDGTHGQYGVEIPLRTRLEKFISEQTKERGGVAIKIPIVCVVLEGGPGTLHTIDNATTNGTPCVVVEGSGRVADVIAQVANLPVSDITISLIQQKLSVFFQEMFETFTESRIVEWTKKIQDIVRRRQLLTVFREGKDGQQDVDVAILQALLKASRSQDHFGHENWDHQLKLAVAWNRVDIARSEIFMDEWQWKPSDLHPTMTAALISNKPEFVKLFLENGVQLKEFVTWDTLLYLYENLDPSCLFHSKLQKVLVEDPERPACAPAAPRLQMHHVAQVLRELLGDFTQPLYPRPRHNDRLRLLLPVPHVKLNVQGVSLRSLYKRSSGHVTFTMDPIRDLLIWAIVQNRRELAGIIWAQSQDCIAAALACSKILKELSKEEEDTDSSEEMLALAEEYEHRAIGVFTECYRKDEERAQKLLTRVSEAWGKTTCLQLALEAKDMKFVSHGGIQAFLTKVWWGQLSVDNGLWRVTLCMLAFPLLLTGLISFREKRLQDVGTPAARARAFFTAPVVVFHLNILSYFAFLCLFAYVLMVDFQPVPSWCECAIYLWLFSLVCEEMRQLFYDPDECGLMKKAALYFSDFWNKLDVGAILLFVAGLTCRLIPATLYPGRVILSLDFILFCLRLMHIFTISKTLGPKIIIVKRMMKDVFFFLFLLAVWVVSFGVAKQAILIHNERRVDWLFRGAVYHSYLTIFGQIPGYIDGVNFNPEHCSPNGTDPYKPKCPESDATQQRPAFPEWLTVLLLCLYLLFTNILLLNLLIAMFNYTFQQVQEHTDQIWKFQRHDLIEEYHGRPAAPPPFILLSHLQLFIKRVVLKTPAKRHKQLKNKLEKNEEAALLSWEIYLKENYLQNRQFQQKQRPEQKIEDISNKVDAMVDLLDLDPLKRSGSMEQRLASLEEQVAQTAQALHWIVRTLRASGFSSEADVPTLASQKAAEEPDAEPGGRKKTEEPGDSYHVNARHLLYPNCPVTRFPVPNEKVPWETEFLIYDPPFYTAERKDAAAMDPMGDTLEPLSTIQYNVVDGLRDRRSFHGPYTVQAGLPLNPMGRTGLRGRGSLSCFGPNHTLYPMVTRWRRNEDGAICRKSIKKMLEVLVVKLPLSEHWALPGGSREPGEMLPRKLKRILRQEHWPSFENLLKCGMEVYKGYMDDPRNTDNAWIETVAVSVHFQDQNDVELNRLNSNLHACDSGASIRWQVVDRRIPLYANHKTLLQKAAAEFGAHY
uniprot
proteins
function
FUNCTION: [Isoform 1]: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:12594222, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:25620041, PubMed:27068538, PubMed:27383051, PubMed:28775320, PubMed:29745897, PubMed:30467180, PubMed:31513012, PubMed:34788616). Functions as a ligand-gated ion channel, gated by intracellular adenosine diphosphate ribose (ADP-ribose), Ca(2+), warm temperature, and oxidative stress (PubMed:19171771, PubMed:25620041, PubMed:28775320, 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). Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening (PubMed:19171771, PubMed:25620041, PubMed:28775320, PubMed:29745897, PubMed:30467180). Extracellular Ca(2+) passes through the channel and increases channel activity (PubMed:19171771). Contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). 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 Ca(2+) 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) (PubMed:22493272). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) 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 Ca(2+) and Zn(2+) levels (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606). {ECO:0000250|UniProtKB:Q91YD4, ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:15561722, ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:19171771, ECO:0000269|PubMed:19454650, ECO:0000269|PubMed:20650899, ECO:0000269|PubMed:20660597, ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:25562606, ECO:0000269|PubMed:25620041, ECO:0000269|PubMed:25918360, ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051, ECO:0000269|PubMed:28775320, ECO:0000269|PubMed:29745897, ECO:0000269|PubMed:30467180, ECO:0000269|PubMed:31513012, ECO:0000269|PubMed:34788616}.; FUNCTION: [Isoform 2]: Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose. {ECO:0000269|PubMed:11960981}.; FUNCTION: [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. {ECO:0000269|PubMed:12594222}.
uniprot
proteins
mass_dalton
171198
uniprot
proteins
mutagenesis
MUTAGEN 215; /note="M->A: Abolishes lowering of temperature threshold for activation in response to reactive oxygen species. Abolishes channel activation in response to ADPR/Ca(2+)."; /evidence="ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:31513012"; MUTAGEN 295; /note="Y->A: Abolishes channel activation in response to ADP-ribose/Ca(2+)."; /evidence="ECO:0000269|PubMed:31513012"; MUTAGEN 302; /note="R->A: No significant effect on channel activity; when associated with A-358. Abolishes channel activation in response to ADP-ribose/Ca(2+)."; /evidence="ECO:0000269|PubMed:30467180, ECO:0000269|PubMed:31513012"; MUTAGEN 358; /note="R->A: No significant effect on channel activity; when associated with A-302."; /evidence="ECO:0000269|PubMed:30467180, ECO:0000269|PubMed:31513012"; MUTAGEN 918; /note="K->A: Decreases in sensitivity to PIP2."; /evidence="ECO:0000269|PubMed:33924946"; MUTAGEN 952; /note="K->A: Strongly reduces channel activity at ph 7.3. Increased residual channel activity after exposure to pH 5.5."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 958; /note="H->A: No effect on channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 961; /note="R->A: Mildly decreases channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 962; /note="R->A: Abolishes channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 968; /note="R->A: Abolishes channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 973; /note="H->A: No effect on channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 980; /note="G->A,C,S: Decreases permeability of Ca(2+) over Na(+)."; /evidence="ECO:0000269|PubMed:34788616"; MUTAGEN 981; /note="Q->A,E,N: Increases the permeability of Ca(2+) over Na(+)."; /evidence="ECO:0000269|PubMed:34788616"; MUTAGEN 982; /note="I->A,E,S: Alters the reversal potential. Increases the permeability of Ca(2+) over Na(+)."; /evidence="ECO:0000269|PubMed:34788616"; MUTAGEN 982; /note="I->L,F: No change in the reversal potential. No change in the ion selectivity to Ca(2+) over Na(+)."; /evidence="ECO:0000269|PubMed:34788616"; MUTAGEN 984..985; /note="GY->LDE: Prevents fast inactivation of the channel."; /evidence="ECO:0000269|PubMed:29745897"; MUTAGEN 984; /note="G->A: No change in the reversal potential. No change in the ion selectivity to Ca(2+) over Na(+)."; /evidence="ECO:0000269|PubMed:34788616"; MUTAGEN 985; /note="Y->A: No change in the reversal potential. No change in the ion selectivity to Ca(2+) over Na(+)."; /evidence="ECO:0000269|PubMed:34788616"; MUTAGEN 995; /note="H->A: Moderately decreases channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 1002; /note="D->A: Strongly increased residual channel activity after exposure to pH 5.5."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 1005; /note="K->A: Decreases channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 1007; /note="K->A: Nearly abolishes channel activity."; /evidence="ECO:0000269|PubMed:20660597"; MUTAGEN 1077; /note="R->A: Decreases in sensitivity to PIP2."; /evidence="ECO:0000269|PubMed:33924946"; MUTAGEN 1228..1503; /note="Missing: Loss of channel activity."; /evidence="ECO:0000269|PubMed:30467180"; MUTAGEN 1397; /note="M->I: Only slight effect on activity."; /evidence="ECO:0000269|PubMed:11804595"; MUTAGEN 1400; /note="R->Q: No effect on channel activity; when associated with G-1407."; /evidence="ECO:0000269|PubMed:25620041"; MUTAGEN 1404; /note="R->Q: Abolishes channel activity."; /evidence="ECO:0000269|PubMed:15561722"; MUTAGEN 1405..1408; /note="ILRQ->EFRE: Decreased channel activity in response to ADP-ribose."; /evidence="ECO:0000269|PubMed:15561722"; MUTAGEN 1407; /note="R->G: No effect on channel activity; when associated with Q-1400."; /evidence="ECO:0000269|PubMed:25620041"; MUTAGEN 1408..1409; /note="QE->KK: Expected to abolish the initially proposed hydrolase activity. Does not abolish channel activity in response to ADP-ribose."; /evidence="ECO:0000269|PubMed:15561722"; MUTAGEN 1408; /note="Q->E: Decreased channel activity."; /evidence="ECO:0000269|PubMed:15561722"; MUTAGEN 1433; /note="R->A: Abolishes channel activation in response to ADP-ribose/Ca(2+)."; /evidence="ECO:0000269|PubMed:31513012
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of TRPM2 at Thr-740 by protein kinase C (PKC) counteracts the effect of cytosolic Ca(2+) and elevates the temperature threshold. {ECO:0000250|UniProtKB:Q91YD4}.
uniprot
proteins
protein_family
LTrpC subfamily
uniprot
proteins
protein_family
TRPM2 sub-subfamily
uniprot
proteins
protein_family
Transient receptor (TC 1.A.4) family
uniprot
proteins
pubmed
10830953
uniprot
proteins
pubmed
11385575
uniprot
proteins
pubmed
11509734
uniprot
proteins
pubmed
11804595
uniprot
proteins
pubmed
11960981
uniprot
proteins
pubmed
12594222
uniprot
proteins
pubmed
15561722
uniprot
proteins
pubmed
15708008
uniprot
proteins
pubmed
16601673
uniprot
proteins
pubmed
19171771
uniprot
proteins
pubmed
19454650
uniprot
proteins
pubmed
20650899
uniprot
proteins
pubmed
20660597
uniprot
proteins
pubmed
22493272
uniprot
proteins
pubmed
25562606
uniprot
proteins
pubmed
25620041
uniprot
proteins
pubmed
25918360
uniprot
proteins
pubmed
27068538
uniprot
proteins
pubmed
27383051
uniprot
proteins
pubmed
28775320
uniprot
proteins
pubmed
29745897
uniprot
proteins
pubmed
30467180
uniprot
proteins
pubmed
31513012
uniprot
proteins
pubmed
33924946
uniprot
proteins
pubmed
34788616
uniprot
proteins
pubmed
9806837
uniprot
proteins
sequence_length
1503
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:15561722, ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:19171771, ECO:0000269|PubMed:20650899, ECO:0000269|PubMed:20660597, ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:25918360, ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051, ECO:0000269|PubMed:30467180}; Multi-pass membrane protein {ECO:0000269|PubMed:30467180}. Perikaryon {ECO:0000250|UniProtKB:E9PTA2}. Cell projection {ECO:0000250|UniProtKB:E9PTA2}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:E9PTA2}. Lysosome {ECO:0000269|PubMed:27068538}. Note=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). {ECO:0000250|UniProtKB:E9PTA2, ECO:0000250|UniProtKB:Q91YD4}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:11960981}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000269|PubMed:12594222}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 796..816; /note="Helical"; /evidence="ECO:0000269|PubMed:30467180"; TRANSMEM 828..848; /note="Helical"; /evidence="ECO:0000269|PubMed:30467180"; TRANSMEM 868..888; /note="Helical"; /evidence="ECO:0000269|PubMed:30467180"; TRANSMEM 897..917; /note="Helical"; /evidence="ECO:0000269|PubMed:30467180"; TRANSMEM 930..950; /note="Helical"; /evidence="ECO:0000269|PubMed:30467180"; TRANSMEM 1023..1044; /note="Helical"; /evidence="ECO:0000269|PubMed:30467180
uniprot
proteins