TRPM2_MOUSE
ID TRPM2_MOUSE Reviewed; 1506 AA.
AC Q91YD4; Q5KTC0;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 2;
DE AltName: Full=Long transient receptor potential channel 2;
DE Short=LTrpC-2;
DE Short=LTrpC2;
DE AltName: Full=Transient receptor potential channel 7;
DE Short=TrpC7;
GN Name=Trpm2; Synonyms=Ltrpc2, Trpc7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Kashuba V.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:BAD83707.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:BAD83707.1};
RC TISSUE=Brain {ECO:0000312|EMBL:BAD83707.1};
RX PubMed=15708008; DOI=10.1016/j.bbrc.2005.01.086;
RA Uemura T., Kudoh J., Noda S., Kanba S., Shimizu N.;
RT "Characterization of human and mouse TRPM2 genes: identification of a novel
RT N-terminal truncated protein specifically expressed in human striatum.";
RL Biochem. Biophys. Res. Commun. 328:1232-1243(2005).
RN [3] {ECO:0000312|EMBL:CAI47592.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:CAI47592.1};
RX PubMed=16260005; DOI=10.1016/j.neuropharm.2005.08.021;
RA Hill K., Tigue N.J., Kelsell R.E., Benham C.D., McNulty S., Schaefer M.,
RA Randall A.D.;
RT "Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in
RT cultured rat striatal neurones.";
RL Neuropharmacology 50:89-97(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI41392.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11804595; DOI=10.1016/s1097-2765(01)00438-5;
RA Hara Y., Wakamori M., Ishii M., Maeno E., Nishida M., Yoshida T.,
RA Yamada H., Shimizu S., Mori E., Kudoh J., Shimizu N., Kurose H., Okada Y.,
RA Imoto K., Mori Y.;
RT "LTRPC2 Ca2+-permeable channel activated by changes in redox status confers
RT susceptibility to cell death.";
RL Mol. Cell 9:163-173(2002).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=16601673; DOI=10.1038/sj.emboj.7601083;
RA Togashi K., Hara Y., Tominaga T., Higashi T., Konishi Y., Mori Y.,
RA Tominaga M.;
RT "TRPM2 activation by cyclic ADP-ribose at body temperature is involved in
RT insulin secretion.";
RL EMBO J. 25:1804-1815(2006).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19454650; DOI=10.1126/scisignal.2000278;
RA Lange I., Yamamoto S., Partida-Sanchez S., Mori Y., Fleig A., Penner R.;
RT "TRPM2 functions as a lysosomal Ca2+-release channel in beta cells.";
RL Sci. Signal. 2:RA23-RA23(2009).
RN [10]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=20921208; DOI=10.2337/db10-0276;
RA Uchida K., Dezaki K., Damdindorj B., Inada H., Shiuchi T., Mori Y.,
RA Yada T., Minokoshi Y., Tominaga M.;
RT "Lack of TRPM2 impaired insulin secretion and glucose metabolisms in
RT mice.";
RL Diabetes 60:119-126(2011).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21753080; DOI=10.1096/fj.10-178483;
RA Sumoza-Toledo A., Lange I., Cortado H., Bhagat H., Mori Y., Fleig A.,
RA Penner R., Partida-Sanchez S.;
RT "Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated
RT lysosomal Ca2+ release.";
RL FASEB J. 25:3529-3542(2011).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21709234; DOI=10.1073/pnas.1010678108;
RA Knowles H., Heizer J.W., Li Y., Chapman K., Ogden C.A., Andreasen K.,
RA Shapland E., Kucera G., Mogan J., Humann J., Lenz L.L., Morrison A.D.,
RA Perraud A.L.;
RT "Transient receptor potential melastatin 2 (TRPM2) ion channel is required
RT for innate immunity against Listeria monocytogenes.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11578-11583(2011).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF MET-214.
RX PubMed=22493272; DOI=10.1073/pnas.1114193109;
RA Kashio M., Sokabe T., Shintaku K., Uematsu T., Fukuta N., Kobayashi N.,
RA Mori Y., Tominaga M.;
RT "Redox signal-mediated sensitization of transient receptor potential
RT melastatin 2 (TRPM2) to temperature affects macrophage functions.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:6745-6750(2012).
RN [14]
RP FUNCTION.
RX PubMed=25562606; DOI=10.1042/bj20140747;
RA Manna P.T., Munsey T.S., Abuarab N., Li F., Asipu A., Howell G., Sedo A.,
RA Yang W., Naylor J., Beech D.J., Jiang L.H., Sivaprasadarao A.;
RT "TRPM2-mediated intracellular Zn2+ release triggers pancreatic beta-cell
RT death.";
RL Biochem. J. 466:537-546(2015).
RN [15]
RP FUNCTION.
RX PubMed=25817999; DOI=10.1074/jbc.m115.649913;
RA Kashio M., Tominaga M.;
RT "Redox signal-mediated enhancement of the temperature sensitivity of
RT transient receptor potential melastatin 2 (TRPM2) elevates glucose-induced
RT insulin secretion from pancreatic islets.";
RL J. Biol. Chem. 290:12435-12442(2015).
RN [16]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=27533035; DOI=10.1038/nature19074;
RA Tan C.H., McNaughton P.A.;
RT "The TRPM2 ion channel is required for sensitivity to warmth.";
RL Nature 536:460-463(2016).
RN [17]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27562954; DOI=10.1126/science.aaf7537;
RA Song K., Wang H., Kamm G.B., Pohle J., de Castro Reis F., Heppenstall P.,
RA Wende H., Siemens J.;
RT "The TRPM2 channel is a hypothalamic heat sensor that limits fever and can
RT drive hypothermia.";
RL Science 353:1393-1398(2016).
CC -!- FUNCTION: Nonselective, voltage-independent cation channel that
CC mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic
CC Ca(2+) levels (PubMed:11804595, PubMed:19454650, PubMed:21753080,
CC PubMed:22493272). Functions as ligand-gated ion channel. Binding of
CC ADP-ribose to the cytoplasmic Nudix domain causes a conformation
CC change; the channel is primed but still requires Ca(2+) binding to
CC trigger channel opening. Extracellular calcium passes through the
CC channel and increases channel activity (By similarity). Also
CC contributes to Ca(2+) release from intracellular stores in response to
CC ADP-ribose (PubMed:21753080). Plays a role in numerous processes that
CC involve signaling via intracellular Ca(2+) levels (PubMed:21753080).
CC Besides, mediates the release of lysosomal Zn(2+) stores in response to
CC reactive oxygen species, leading to increased cytosolic Zn(2+) levels
CC (By similarity). Activated by moderate heat (35 to 40 degrees Celsius)
CC (PubMed:27533035, PubMed:27562954). Activated by intracellular ADP-
CC ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative
CC stress caused by reactive oxygen or nitrogen species (PubMed:19454650,
CC PubMed:21753080, PubMed:22493272). The precise physiological activators
CC are under debate; the true, physiological activators may be ADP-ribose
CC and ADP-ribose-2'-phosphate. Activation by ADP-ribose and beta-NAD is
CC strongly increased by moderate heat (35 to 40 degrees Celsius) (By
CC similarity). Likewise, reactive oxygen species lower the threshold for
CC activation by moderate heat (37 degrees Celsius) (PubMed:22493272,
CC PubMed:25817999). Plays a role in mediating behavorial and
CC physiological responses to moderate heat and thereby contributes to
CC body temperature homeostasis (PubMed:27533035, PubMed:27562954). Plays
CC a role in insulin secretion, a process that requires increased
CC cytoplasmic Ca(2+) levels (PubMed:20921208, PubMed:25817999). Required
CC for normal IFNG and cytokine secretion and normal innate immune
CC immunity in response to bacterial infection (PubMed:21709234). Required
CC for normal phagocytosis and cytokine release by macrophages exposed to
CC zymosan (in vitro) (PubMed:22493272). Plays a role in dendritic cell
CC differentiation and maturation, and in dendritic cell chemotaxis via
CC its role in regulating cytoplasmic Ca(2+) levels (PubMed:21753080).
CC Plays a role in the regulation of the reorganization of the actin
CC cytoskeleton and filopodia formation in response to reactive oxygen
CC species via its function in increasing cytoplasmic Ca(2+) and Zn(2+)
CC levels (By similarity). Confers susceptibility to cell death following
CC oxidative stress (PubMed:25562606). {ECO:0000250|UniProtKB:O94759,
CC ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:19454650,
CC ECO:0000269|PubMed:21753080, ECO:0000269|PubMed:22493272,
CC ECO:0000269|PubMed:25562606, ECO:0000269|PubMed:25817999,
CC ECO:0000269|PubMed:27533035, ECO:0000269|PubMed:27562954}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:O94759}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11804595,
CC ECO:0000269|PubMed:19454650, ECO:0000269|PubMed:21753080,
CC ECO:0000269|PubMed:22493272}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O94759}. Perikaryon
CC {ECO:0000250|UniProtKB:E9PTA2}. Cell projection
CC {ECO:0000250|UniProtKB:E9PTA2}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:21753080}. Lysosome {ECO:0000269|PubMed:21753080}.
CC Note=Detected at the cell membrane and in intracellular vesicles in
CC cortical neurons. Detected on neuronal cell bodies and neurites (By
CC similarity). Detected on the cell membrane in polymorphonuclear
CC neutrophils (PubMed:21753080). Detected on cytoplasmic vesicles and
CC lysosomes in immature bone marrow dendritic cells (PubMed:21753080).
CC {ECO:0000250|UniProtKB:E9PTA2, ECO:0000269|PubMed:21753080}.
CC -!- TISSUE SPECIFICITY: Detected in the preoptic area of the hypothalamus,
CC a brain area involved in body temperature control (PubMed:27562954).
CC Detected in beta-cells in pancreas islets (at protein level)
CC (PubMed:16601673, PubMed:20921208). Detected in brain cortex, striatum,
CC hippocampus CA1, CA2 and CA3 layers, and in the Purkinje cell layer in
CC cerebellum (PubMed:15708008). Widely expressed, with highest levels in
CC lung, spleen, eye and brain (PubMed:11804595). Detected in dendritic
CC cells and in polymorphonuclear neutrophils (PubMed:21753080).
CC {ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:15708008,
CC ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:20921208,
CC ECO:0000269|PubMed:21753080, ECO:0000269|PubMed:27562954}.
CC -!- DOMAIN: The cytosolic nudix box binds ADP-ribose and is required for
CC channel activation by ADP-ribose. {ECO:0000250|UniProtKB:O94759}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice display no obvious phenotype, but
CC display increased blood glucose levels when fed ad libitum
CC (PubMed:20921208). After oral or intraperitoneal glucose
CC administration, they display increased blood glucose and lower plasma
CC insulin levels; basal fasting glucose and insulin levels are not
CC altered (PubMed:20921208). Ca(2+) influx into beta-cells is unchanged
CC under basal conditions or upon stimulation with glucose up to 8.3 mM;
CC Ca(2+) influx is decreased upon stimulation with high glucose levels
CC (16.7 mM) (PubMed:20921208). Likewise, insulin secretion is decreased
CC only upon stimulation with 11.2 or 16.7 mM glucose, but not in response
CC to more moderate glucose levels (PubMed:20921208). Mutant mice have a
CC reduced number of neurons that are activated by warm temperature (34 to
CC 43 degrees Celsius) in their dorsal root ganglia and superior cervical
CC ganglia (PubMed:27533035). Mutant mice show altered behavorial
CC responses to environmental temperature; contrary to wild-type they show
CC no preference for a cooler environment when exposed to 38 degrees
CC Celsius (PubMed:27533035). Besides, they spend less time than wild-type
CC in a cooler environment (23 degrees Celsius) (PubMed:27533035). Mutant
CC mice develop higher fever in response to prostaglandin E2 injection
CC into the preoptic area of the hypothalamus, a brain area involved in
CC body temperature control (PubMed:27562954). Mutant mice display a
CC defective innate immune response and are highly susceptible to
CC infection by L.monocytogenes (PubMed:21709234). They are unable to
CC contain the bacterial infection; contrary to wild-type, they die within
CC a few days after infection (PubMed:21709234). The defective immune
CC response is due to impaired secretion of Il12b and IFNG; mice are
CC rescued by treatment with recombinant IFNG (PubMed:21709234).
CC {ECO:0000269|PubMed:20921208, ECO:0000269|PubMed:21709234,
CC ECO:0000269|PubMed:27533035}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC subfamily. TRPM2 sub-subfamily. {ECO:0000305}.
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DR EMBL; AJ344343; CAC69081.1; -; mRNA.
DR EMBL; AB166747; BAD83707.1; -; mRNA.
DR EMBL; AJ878415; CAI47592.1; -; mRNA.
DR EMBL; AC153507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC158612; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466553; EDL31768.1; -; Genomic_DNA.
DR EMBL; BC141391; AAI41392.1; -; mRNA.
DR CCDS; CCDS48611.1; -.
DR RefSeq; NP_612174.2; NM_138301.2.
DR AlphaFoldDB; Q91YD4; -.
DR SMR; Q91YD4; -.
DR STRING; 10090.ENSMUSP00000101040; -.
DR iPTMnet; Q91YD4; -.
DR PhosphoSitePlus; Q91YD4; -.
DR EPD; Q91YD4; -.
DR MaxQB; Q91YD4; -.
DR PaxDb; Q91YD4; -.
DR PRIDE; Q91YD4; -.
DR ProteomicsDB; 298138; -.
DR Antibodypedia; 10236; 311 antibodies from 32 providers.
DR DNASU; 28240; -.
DR Ensembl; ENSMUST00000105401; ENSMUSP00000101040; ENSMUSG00000009292.
DR GeneID; 28240; -.
DR KEGG; mmu:28240; -.
DR UCSC; uc007fwl.2; mouse.
DR CTD; 7226; -.
DR MGI; MGI:1351901; Trpm2.
DR VEuPathDB; HostDB:ENSMUSG00000009292; -.
DR eggNOG; KOG3614; Eukaryota.
DR eggNOG; KOG4195; Eukaryota.
DR GeneTree; ENSGT00940000156404; -.
DR InParanoid; Q91YD4; -.
DR OMA; DGTHGHY; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q91YD4; -.
DR TreeFam; TF314204; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 28240; 5 hits in 77 CRISPR screens.
DR PRO; PR:Q91YD4; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q91YD4; protein.
DR Bgee; ENSMUSG00000009292; Expressed in granulocyte and 126 other tissues.
DR ExpressionAtlas; Q91YD4; baseline and differential.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; ISS:UniProtKB.
DR GO; GO:0099604; F:ligand-gated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IDA:MGI.
DR GO; GO:0072571; F:mono-ADP-D-ribose binding; ISS:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; IEA:UniProtKB-KW.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IMP:UniProtKB.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP:UniProtKB.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:0071415; P:cellular response to purine-containing compound; IMP:UniProtKB.
DR GO; GO:0071502; P:cellular response to temperature stimulus; IMP:UniProtKB.
DR GO; GO:0002407; P:dendritic cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0097028; P:dendritic cell differentiation; IMP:UniProtKB.
DR GO; GO:0044849; P:estrous cycle; IEA:Ensembl.
DR GO; GO:0006828; P:manganese ion transport; IDA:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
DR GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0009408; P:response to heat; IMP:UniProtKB.
DR GO; GO:0033194; P:response to hydroperoxide; IDA:MGI.
DR GO; GO:0014074; P:response to purine-containing compound; ISO:MGI.
DR GO; GO:0001659; P:temperature homeostasis; IMP:UniProtKB.
DR GO; GO:0071577; P:zinc ion transmembrane transport; ISS:UniProtKB.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR029594; TRPM2.
DR InterPro; IPR041491; TRPM_SLOG.
DR PANTHER; PTHR13800:SF2; PTHR13800:SF2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF18139; LSDAT_euk; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane;
KW Cell projection; Cytoplasmic vesicle; Disulfide bond; Ion channel;
KW Ion transport; Lysosome; Membrane; Metal-binding; Reference proteome;
KW Sodium; Sodium channel; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1506
FT /note="Transient receptor potential cation channel
FT subfamily M member 2"
FT /id="PRO_0000215327"
FT TOPO_DOM 1..750
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 751..767
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 768..792
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 793..813
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 814..824
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 825..845
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 846..864
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 865..885
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 886..893
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 894..914
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 915..926
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 927..947
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 948..967
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 968..982
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 983..1019
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1020..1041
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 1042..1076
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 1077..1095
FT /evidence="ECO:0000250|UniProtKB:O94759"
FT TOPO_DOM 1096..1506
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 1350..1501
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1386..1407
FT /note="Nudix box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT BINDING 840
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IMY7"
FT BINDING 843
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IMY7"
FT BINDING 866
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IMY7"
FT BINDING 1070
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IMY7"
FT DISULFID 993..1005
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IMY7"
FT MUTAGEN 214
FT /note="M->A: Abolishes lowering of temperature threshold
FT for activation in response to reactive oxygen species."
FT /evidence="ECO:0000269|PubMed:22493272"
FT CONFLICT 843
FT /note="Q -> QY (in Ref. 1; CAC69081)"
SQ SEQUENCE 1506 AA; 172202 MW; E340C2F4DED121F4 CRC64;
MESLDRRRTG SEQEEGFGVQ SRRATDLGMV PNLRRSNSSL CKSRRFLCSF SSEKQENLSS
WIPENIKKKE CVYFVESSKL SDAGKVVCAC GYTHEQHLEV AIKPHTFQGK EWDPKKHVQE
MPTDAFGDIV FTDLSQKVGK YVRVSQDTPS SVIYQLMTQH WGLDVPNLLI SVTGGAKNFN
MKLRLKSIFR RGLVKVAQTT GAWIITGGSH TGVMKQVGEA VRDFSLSSSC KEGEVITIGV
ATWGTIHNRE GLIHPMGGFP AEYMLDEEGQ GNLTCLDSNH SHFILVDDGT HGQYGVEIPL
RTKLEKFISE QTKERGGVAI KIPIVCVVLE GGPGTLHTIY NAINNGTPCV IVEGSGRVAD
VIAQVATLPV SEITISLIQQ KLSIFFQEMF ETFTENQIVE WTKKIQDIVR RRQLLTIFRE
GKDGQQDVDV AILQALLKAS RSQDHFGHEN WDHQLKLAVA WNRVDIARSE IFTDEWQWKP
ADLHPMMTAA LISNKPEFVR LFLENGVRLK EFVTWDTLLC LYENLEPSCL FHSKLQKVLA
EEQRLAYASA TPRLHMHHVA QVLRELLGDS TQLLYPRPRY TDRPRLSMTV PHIKLNVQGV
SLRSLYKRST GHVTFTIDPV RDLLIWAVIQ NHRELAGIIW AQSQDCTAAA LACSKILKEL
SKEEEDTDSS EEMLALADEF EHRAIGVFTE CYRKDEERAQ KLLVRVSEAW GKTTCLQLAL
EAKDMKFVSH GGIQAFLTKV WWGQLCVDNG LWRIILCMLA FPLLFTGFIS FREKRLQALC
RPARVRAFFN APVVIFHMNI LSYFAFLCLF AYVLMVDFQP SPSWCEYLIY LWLFSLVCEE
TRQLFYDPDG CGLMKMASLY FSDFWNKLDV GAILLFIVGL TCRLIPATLY PGRIILSLDF
IMFCLRLMHI FTISKTLGPK IIIVKRMMKD VFFFLFLLAV WVVSFGVAKQ AILIHNESRV
DWIFRGVVYH SYLTIFGQIP TYIDGVNFSM DQCSPNGTDP YKPKCPESDW TGQAPAFPEW
LTVTLLCLYL LFANILLLNL LIAMFNYTFQ EVQEHTDQIW KFQRHDLIEE YHGRPPAPPP
LILLSHLQLL IKRIVLKIPA KRHKQLKNKL EKNEETALLS WELYLKENYL QNQQYQQKQR
PEQKIQDISE KVDTMVDLLD MDQVKRSGST EQRLASLEEQ VTQVTRALHW IVTTLKDSGF
GSGAGALTLA PQRAFDEPDA ELSIRRKVEE PGDGYHVSAR HLLYPNARIM RFPVPNEKVP
WAAEFLIYDP PFYTAEKDVA LTDPVGDTAE PLSKISYNVV DGPTDRRSFH GVYVVEYGFP
LNPMGRTGLR GRGSLSWFGP NHTLQPVVTR WKRNQGGAIC RKSVRKMLEV LVMKLPRSEH
WALPGGSREP GEMLPRKLKR VLRQEFWVAF ETLLMQGTEV YKGYVDDPRN TDNAWIETVA
VSIHFQDQND MELKRLEENL HTHDPKELTR DLKLSTEWQV VDRRIPLYAN HKTILQKVAS
LFGAHF
