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Database: UniProt
Entry: TRPM2_HUMAN
LinkDB: TRPM2_HUMAN
Original site: TRPM2_HUMAN 
ID   TRPM2_HUMAN             Reviewed;        1503 AA.
AC   O94759; D3DSL6; Q5KTC2; Q6J3P5; Q96KN6; Q96Q93;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-2007, sequence version 2.
DT   25-OCT-2017, entry version 167.
DE   RecName: Full=Transient receptor potential cation channel subfamily M member 2;
DE   AltName: Full=Estrogen-responsive element-associated gene 1 protein {ECO:0000303|Ref.9};
DE   AltName: Full=Long transient receptor potential channel 2 {ECO:0000303|PubMed:11960981};
DE            Short=LTrpC-2;
DE            Short=LTrpC2 {ECO:0000303|PubMed:11960981};
DE   AltName: Full=Transient receptor potential channel 7 {ECO:0000303|PubMed:9806837};
DE            Short=TrpC7 {ECO:0000303|PubMed:9806837};
DE   AltName: Full=Transient receptor potential melastatin 2 {ECO:0000303|PubMed:27383051};
GN   Name=TRPM2;
GN   Synonyms=EREG1 {ECO:0000303|Ref.9}, KNP3,
GN   LTRPC2 {ECO:0000303|PubMed:11960981},
GN   TRPC7 {ECO:0000303|PubMed:9806837};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-1189.
RC   TISSUE=Brain;
RX   PubMed=9806837; DOI=10.1006/geno.1998.5551;
RA   Nagamine K., Kudoh J., Minoshima S., Kawasaki K., Asakawa S., Ito F.,
RA   Shimizu N.;
RT   "Molecular cloning of a novel putative Ca2+ channel protein (TRPC7)
RT   highly expressed in brain.";
RL   Genomics 54:124-131(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-1189, FUNCTION
RP   (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND REGULATION BY OXIDATIVE
RP   STRESS.
RC   TISSUE=Promyelocytic leukemia;
RX   PubMed=11960981; DOI=10.1074/jbc.M112096200;
RA   Wehage E., Eisfeld J., Heiner I., Juengling E., Zitt C., Lueckhoff A.;
RT   "Activation of the cation channel long transient receptor potential
RT   channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a
RT   mode of activation independent of ADP-ribose.";
RL   J. Biol. Chem. 277:23150-23156(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT ARG-1189, FUNCTION
RP   (ISOFORMS 1 AND 3), INTERACTION BETWEEN ISOFORMS 1 AND 3, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Bone marrow;
RX   PubMed=12594222; DOI=10.1074/jbc.M300298200;
RA   Zhang W., Chu X., Tong Q., Cheung J.Y., Conrad K., Masker K.,
RA   Miller B.A.;
RT   "A novel TRPM2 isoform inhibits calcium influx and susceptibility to
RT   cell death.";
RL   J. Biol. Chem. 278:16222-16229(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-1189.
RC   TISSUE=Brain;
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
RT   novel N-terminal truncated protein specifically expressed in human
RT   striatum.";
RL   Biochem. Biophys. Res. Commun. 328:1232-1243(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-1189.
RA   Hayes P.D.;
RT   "Cloning of the human TRPM2.";
RL   Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-52; ILE-166;
RP   MET-385; GLU-543; GLU-780; TRP-1199; GLY-1201; SER-1249; MET-1347;
RP   LYS-1359; MET-1368 AND SER-1438.
RG   NIEHS SNPs program;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T.,
RA   Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA   Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA   Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA   Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA   Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA   Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA   Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA   Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA   Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA   Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA   Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1190-1503.
RA   Hiroi H., Muramatsu M., Inoue S.;
RT   "Molecular cloning of a novel estrogen responsive gene, estrogen
RT   responsive element associated gene 1 (EREG1), which contains MutT like
RT   domain.";
RL   Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   FUNCTION, REGULATION BY ADP-RIBOSE, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND DOMAIN.
RX   PubMed=11385575; DOI=10.1038/35079100;
RA   Perraud A.-L., Fleig A., Dunn C.A., Bagley L.A., Launay P.,
RA   Schmitz C., Stokes A.J., Zhu Q., Bessman M.J., Penner R., Kinet J.-P.,
RA   Scharenberg A.M.;
RT   "ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by
RT   Nudix motif homology.";
RL   Nature 411:595-599(2001).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, REGULATION BY PYRIMIDINE NUCLEOTIDES,
RP   ENZYME REGULATION, AND TISSUE SPECIFICITY.
RX   PubMed=11509734; DOI=10.1126/science.1062473;
RA   Sano Y., Inamura K., Miyake A., Mochizuki S., Yokoi H., Matsushime H.,
RA   Furuichi K.;
RT   "Immunocyte Ca2+ influx system mediated by LTRPC2.";
RL   Science 293:1327-1330(2001).
RN   [12]
RP   FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, AND MUTAGENESIS OF
RP   MET-1397.
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.,
RA   Okada Y., Imoto K., Mori Y.;
RT   "LTRPC2 Ca2+-permeable channel activated by changes in redox status
RT   confers susceptibility to cell death.";
RL   Mol. Cell 9:163-173(2002).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ARG-1404;
RP   1405-ILE--GLN-1408; 1408-GLN-GLU-1409 AND GLN-1408.
RX   PubMed=15561722; DOI=10.1074/jbc.M411446200;
RA   Perraud A.L., Takanishi C.L., Shen B., Kang S., Smith M.K.,
RA   Schmitz C., Knowles H.M., Ferraris D., Li W., Zhang J., Stoddard B.L.,
RA   Scharenberg A.M.;
RT   "Accumulation of free ADP-ribose from mitochondria mediates oxidative
RT   stress-induced gating of TRPM2 cation channels.";
RL   J. Biol. Chem. 280:6138-6148(2005).
RN   [14]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
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
RT   in insulin secretion.";
RL   EMBO J. 25:1804-1815(2006).
RN   [15]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=19171771; DOI=10.1085/jgp.200810109;
RA   Csanady L., Toerocsik B.;
RT   "Four Ca2+ ions activate TRPM2 channels by binding in deep crevices
RT   near the pore but intracellularly of the gate.";
RL   J. Gen. Physiol. 133:189-203(2009).
RN   [16]
RP   FUNCTION.
RX   PubMed=19454650; DOI=10.1126/scisignal.2000278;
RA   Lange I., Yamamoto S., Partida-Sanchez S., Mori Y., Fleig A.,
RA   Penner R.;
RT   "TRPM2 functions as a lysosomal Ca2+-release channel in beta cells.";
RL   Sci. Signal. 2:RA23-RA23(2009).
RN   [17]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=20650899; DOI=10.1074/jbc.M109.066464;
RA   Toth B., Csanady L.;
RT   "Identification of direct and indirect effectors of the transient
RT   receptor potential melastatin 2 (TRPM2) cation channel.";
RL   J. Biol. Chem. 285:30091-30102(2010).
RN   [18]
RP   FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, AND MUTAGENESIS OF
RP   LYS-952; HIS-958; ARG-961; ARG-962; ARG-968; HIS-973; HIS-995;
RP   ASP-1002; LYS-1005 AND LYS-1007.
RX   PubMed=20660597; DOI=10.1074/jbc.M110.139774;
RA   Yang W., Zou J., Xia R., Vaal M.L., Seymour V.A., Luo J., Beech D.J.,
RA   Jiang L.H.;
RT   "State-dependent inhibition of TRPM2 channel by acidic pH.";
RL   J. Biol. Chem. 285:30411-30418(2010).
RN   [19]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF MET-215.
RX   PubMed=22493272; DOI=10.1073/pnas.1114193109;
RA   Kashio M., Sokabe T., Shintaku K., Uematsu T., Fukuta N.,
RA   Kobayashi N., 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   [20]
RP   FUNCTION.
RX   PubMed=25562606; DOI=10.1042/BJ20140747;
RA   Manna P.T., Munsey T.S., Abuarab N., Li F., Asipu A., Howell G.,
RA   Sedo A., Yang W., Naylor J., Beech D.J., Jiang L.H.,
RA   Sivaprasadarao A.;
RT   "TRPM2-mediated intracellular Zn2+ release triggers pancreatic beta-
RT   cell death.";
RL   Biochem. J. 466:537-546(2015).
RN   [21]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=25918360; DOI=10.1085/jgp.201511377;
RA   Toth B., Iordanov I., Csanady L.;
RT   "Ruling out pyridine dinucleotides as true TRPM2 channel activators
RT   reveals novel direct agonist ADP-ribose-2'-phosphate.";
RL   J. Gen. Physiol. 145:419-430(2015).
RN   [22]
RP   LACK OF CATALYTIC ACTIVITY, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=27383051; DOI=10.7554/eLife.17600;
RA   Iordanov I., Mihalyi C., Toth B., Csanady L.;
RT   "The proposed channel-enzyme transient receptor potential melastatin 2
RT   does not possess ADP ribose hydrolase activity.";
RL   Elife 5:0-0(2016).
RN   [23]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=27068538; DOI=10.1242/jcs.179796;
RA   Li F., Abuarab N., Sivaprasadarao A.;
RT   "Reciprocal regulation of actin cytoskeleton remodelling and cell
RT   migration by Ca2+ and Zn2+: role of TRPM2 channels.";
RL   J. Cell Sci. 129:2016-2029(2016).
CC   -!- FUNCTION: Isoform 1: Nonselective, voltage-independent cation
CC       channel that mediates Na(+) and Ca(2+) influx, leading to
CC       increased cytoplasmic Ca(2+) levels (PubMed:11960981,
CC       PubMed:12594222, PubMed:11385575, PubMed:11509734,
CC       PubMed:11804595, PubMed:15561722, PubMed:16601673,
CC       PubMed:19171771, PubMed:20660597, PubMed:27383051,
CC       PubMed:27068538). Extracellular calcium passes through the channel
CC       and increases channel activity by binding to the cytoplasmic
CC       domain and stabilizing the channel in an open conformation
CC       (PubMed:19171771). Also contributes to Ca(2+) release from
CC       intracellular stores in response to ADP-ribose (PubMed:19454650).
CC       Plays a role in numerous processes that involve signaling via
CC       intracellular Ca(2+) levels (Probable). Besides, mediates the
CC       release of lysosomal Zn(2+) stores in response to reactive oxygen
CC       species, leading to increased cytosolic Zn(2+) levels
CC       (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35
CC       to 40 degrees Celsius) (PubMed:16601673). Activated by
CC       intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds,
CC       and by oxidative stress caused by reactive oxygen or nitrogen
CC       species (PubMed:11960981, PubMed:11385575, PubMed:11509734,
CC       PubMed:11804595, PubMed:15561722, PubMed:16601673,
CC       PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise
CC       physiological activators are under debate; the true, physiological
CC       activators may be ADP-ribose and ADP-ribose-2'-phosphate
CC       (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and
CC       beta-NAD is strongly increased by moderate heat (35 to 40 degrees
CC       Celsius) (PubMed:16601673). Likewise, reactive oxygen species
CC       lower the threshold for activation by moderate heat (37 degrees
CC       Celsius) (PubMed:22493272). Plays a role in mediating behavorial
CC       and physiological responses to moderate heat and thereby
CC       contributes to body temperature homeostasis. Plays a role in
CC       insulin secretion, a process that requires increased cytoplasmic
CC       Ca(2+) levels (By similarity). Required for normal IFNG and
CC       cytokine secretion and normal innate immune immunity in response
CC       to bacterial infection. Required for normal phagocytosis and
CC       cytokine release by macrophages exposed to zymosan (in vitro).
CC       Plays a role in dendritic cell differentiation and maturation, and
CC       in dendritic cell chemotaxis via its role in regulating
CC       cytoplasmic Ca(2+) levels (By similarity). Plays a role in the
CC       regulation of the reorganization of the actin cytoskeleton and
CC       filopodia formation in response to reactive oxygen species via its
CC       role in increasing cytoplasmic Ca(2+) and Zn(2+) levels
CC       (PubMed:27068538). Confers susceptibility to cell death following
CC       oxidative stress (PubMed:12594222, PubMed:25562606).
CC       {ECO:0000250|UniProtKB:Q91YD4, ECO:0000269|PubMed:11385575,
CC       ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595,
CC       ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222,
CC       ECO:0000269|PubMed:15561722, ECO:0000269|PubMed:16601673,
CC       ECO:0000269|PubMed:19171771, ECO:0000269|PubMed:19454650,
CC       ECO:0000269|PubMed:20650899, ECO:0000269|PubMed:20660597,
CC       ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:25562606,
CC       ECO:0000269|PubMed:25918360, ECO:0000269|PubMed:27068538,
CC       ECO:0000269|PubMed:27383051, ECO:0000305}.
CC   -!- FUNCTION: Isoform 2: Lacks cation channel activity. Does not
CC       mediate cation transport in response to oxidative stress or ADP-
CC       ribose. {ECO:0000269|PubMed:11960981}.
CC   -!- FUNCTION: Isoform 3: Lacks cation channel activity and negatively
CC       regulates the channel activity of isoform 1. Negatively regulates
CC       susceptibility to cell death in reposponse to oxidative stress.
CC       {ECO:0000269|PubMed:12594222}.
CC   -!- ENZYME REGULATION: Inactivated by exposure to extracellular pH
CC       between 4.0 and 6.5; irreversibly inactivated when open channels
CC       are exposed to extracellular pH between 4.0 and 6.5, while pre-
CC       exposure of closed channels to extracellular pH 5.5 gives rise to
CC       currents that rapidly inactivate, but protects against
CC       irreversible inactivation (PubMed:20660597). Inactivated by
CC       intracellular ATP (PubMed:11509734). Activated by arachidonic acid
CC       (PubMed:11804595). {ECO:0000269|PubMed:11509734,
CC       ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:20660597}.
CC   -!- SUBUNIT: Isoform 1 can interact with isoform 3. This interaction
CC       decreases calcium influx through isoform 1 and suppresses
CC       susceptibility to oxidative stress-induced cell death.
CC       {ECO:0000269|PubMed:12594222}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11385575,
CC       ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595,
CC       ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:15561722,
CC       ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:19171771,
CC       ECO:0000269|PubMed:20650899, ECO:0000269|PubMed:20660597,
CC       ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:25918360,
CC       ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051}; Multi-
CC       pass membrane protein {ECO:0000255}. Perikaryon
CC       {ECO:0000250|UniProtKB:E9PTA2}. Cell projection
CC       {ECO:0000250|UniProtKB:E9PTA2}. Cytoplasmic vesicle
CC       {ECO:0000250|UniProtKB:E9PTA2}. Lysosome
CC       {ECO:0000269|PubMed:27068538}. Note=Detected at the cell membrane
CC       and in intracellular vesicles in cortical neurons. Detected on
CC       neuronal cell bodies and neurites (By similarity). Detected on the
CC       cell membrane in polymorphonuclear neutrophils. Detected on
CC       cytoplasmic vesicles and lysosomes in immature bone marrow
CC       dendritic cells (By similarity). {ECO:0000250|UniProtKB:E9PTA2,
CC       ECO:0000250|UniProtKB:Q91YD4}.
CC   -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane
CC       {ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: Isoform 2: Cell membrane
CC       {ECO:0000269|PubMed:11960981}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: Isoform 3: Cell membrane
CC       {ECO:0000269|PubMed:12594222}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=TRPM2-L;
CC         IsoId=O94759-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O94759-2; Sequence=VSP_006574, VSP_006575;
CC       Name=3; Synonyms=TRPM2-S;
CC         IsoId=O94759-3; Sequence=VSP_013018;
CC   -!- TISSUE SPECIFICITY: Highly expressed in brain and peripheral blood
CC       cells, such as neutrophils. Also detected in bone marrow, spleen,
CC       heart, liver and lung. Isoform 2 is found in neutrophil
CC       granulocytes. {ECO:0000269|PubMed:11385575,
CC       ECO:0000269|PubMed:11509734}.
CC   -!- DOMAIN: The cytosolic nudix box binds ADP-ribose and is required
CC       for channel activation by ADP-ribose (PubMed:15561722,
CC       PubMed:16601673). {ECO:0000269|PubMed:15561722,
CC       ECO:0000269|PubMed:16601673}.
CC   -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC       LTrpC subfamily. TRPM2 sub-subfamily. {ECO:0000305}.
CC   -!- CAUTION: The isolated nudix hydrolase domain was shown to have low
CC       catalytic activity with ADP-ribose upon heterologous expression
CC       (PubMed:11385575). However, a more recent publication demonstrates
CC       that the nudix hydrolase domain lacks enzyme activity and suggests
CC       that spontaneous degradation of the substrate underlies the
CC       previously reported low activity (PubMed:27383051).
CC       {ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:27383051}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB64300.1; Type=Frameshift; Positions=1227, 1237; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/trpm2/";
DR   EMBL; AB001535; BAA34700.1; -; mRNA.
DR   EMBL; AJ417076; CAD01139.1; -; mRNA.
DR   EMBL; AY603182; AAT12288.1; -; mRNA.
DR   EMBL; AB166745; BAD83705.1; -; mRNA.
DR   EMBL; AJ878416; CAI47593.1; -; mRNA.
DR   EMBL; DQ012935; AAY22174.1; -; Genomic_DNA.
DR   EMBL; AP001754; BAA95563.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09426.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09427.1; -; Genomic_DNA.
DR   EMBL; AB017549; BAB64300.1; ALT_FRAME; mRNA.
DR   CCDS; CCDS13710.1; -. [O94759-1]
DR   RefSeq; NP_001307279.1; NM_001320350.1.
DR   RefSeq; NP_001307280.1; NM_001320351.1.
DR   RefSeq; NP_003298.1; NM_003307.3.
DR   RefSeq; XP_005261228.1; XM_005261171.3. [O94759-1]
DR   UniGene; Hs.369759; -.
DR   ProteinModelPortal; O94759; -.
DR   SMR; O94759; -.
DR   IntAct; O94759; 1.
DR   STRING; 9606.ENSP00000300482; -.
DR   BindingDB; O94759; -.
DR   ChEMBL; CHEMBL1250402; -.
DR   GuidetoPHARMACOLOGY; 494; -.
DR   TCDB; 1.A.4.5.5; the transient receptor potential ca(2+) channel (trp-cc) family.
DR   iPTMnet; O94759; -.
DR   PhosphoSitePlus; O94759; -.
DR   BioMuta; TRPM2; -.
DR   EPD; O94759; -.
DR   PaxDb; O94759; -.
DR   PeptideAtlas; O94759; -.
DR   PRIDE; O94759; -.
DR   Ensembl; ENST00000300481; ENSP00000300481; ENSG00000142185. [O94759-2]
DR   Ensembl; ENST00000300482; ENSP00000300482; ENSG00000142185. [O94759-1]
DR   Ensembl; ENST00000397928; ENSP00000381023; ENSG00000142185. [O94759-1]
DR   GeneID; 7226; -.
DR   KEGG; hsa:7226; -.
DR   UCSC; uc002zet.1; human. [O94759-1]
DR   CTD; 7226; -.
DR   DisGeNET; 7226; -.
DR   EuPathDB; HostDB:ENSG00000142185.16; -.
DR   GeneCards; TRPM2; -.
DR   HGNC; HGNC:12339; TRPM2.
DR   HPA; HPA030976; -.
DR   HPA; HPA035260; -.
DR   MIM; 603749; gene.
DR   neXtProt; NX_O94759; -.
DR   OpenTargets; ENSG00000142185; -.
DR   PharmGKB; PA37012; -.
DR   eggNOG; KOG3614; Eukaryota.
DR   eggNOG; KOG4195; Eukaryota.
DR   eggNOG; ENOG410XR5B; LUCA.
DR   GeneTree; ENSGT00760000119127; -.
DR   HOGENOM; HOG000236350; -.
DR   HOVERGEN; HBG055825; -.
DR   InParanoid; O94759; -.
DR   KO; K04977; -.
DR   PhylomeDB; O94759; -.
DR   TreeFam; TF314204; -.
DR   Reactome; R-HSA-3295583; TRP channels.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   GeneWiki; TRPM2; -.
DR   GenomeRNAi; 7226; -.
DR   PRO; PR:O94759; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   Bgee; ENSG00000142185; -.
DR   CleanEx; HS_TRPC7; -.
DR   CleanEx; HS_TRPM2; -.
DR   ExpressionAtlas; O94759; baseline and differential.
DR   Genevisible; O94759; HS.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR   GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR   GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR   GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR   GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR   GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB.
DR   GO; GO:0015278; F:calcium-release channel activity; IMP:UniProtKB.
DR   GO; GO:0005261; F:cation channel activity; IMP:UniProtKB.
DR   GO; GO:0099604; F:ligand-gated calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0005272; F:sodium channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0098703; P:calcium ion import across plasma membrane; ISS:UniProtKB.
DR   GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IMP:UniProtKB.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0006816; P:calcium ion transport; TAS:ProtInc.
DR   GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
DR   GO; GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:UniProtKB.
DR   GO; GO:0071415; P:cellular response to purine-containing compound; ISS:UniProtKB.
DR   GO; GO:0071502; P:cellular response to temperature stimulus; ISS:UniProtKB.
DR   GO; GO:0002407; P:dendritic cell chemotaxis; ISS:UniProtKB.
DR   GO; GO:0097028; P:dendritic cell differentiation; ISS:UniProtKB.
DR   GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR   GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR   GO; GO:0051489; P:regulation of filopodium assembly; IMP:UniProtKB.
DR   GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR   GO; GO:0014074; P:response to purine-containing compound; IMP:UniProtKB.
DR   GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB.
DR   GO; GO:0071577; P:zinc II ion transmembrane transport; IMP:UniProtKB.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR000086; NUDIX_hydrolase_dom.
DR   InterPro; IPR015797; NUDIX_hydrolase_dom-like.
DR   InterPro; IPR029594; TRPM2.
DR   PANTHER; PTHR13800:SF2; PTHR13800:SF2; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   SUPFAM; SSF55811; SSF55811; 1.
DR   PROSITE; PS51462; NUDIX; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW   Cell membrane; Cell projection; Complete proteome;
KW   Cytoplasmic vesicle; Ion channel; Ion transport; Lysosome; Membrane;
KW   Polymorphism; Reference proteome; Sodium; Sodium channel;
KW   Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN         1   1503       Transient receptor potential cation
FT                                channel subfamily M member 2.
FT                                /FTId=PRO_0000215326.
FT   TOPO_DOM      1    752       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    753    773       Helical. {ECO:0000255}.
FT   TOPO_DOM    774    795       Extracellular. {ECO:0000255}.
FT   TRANSMEM    796    816       Helical. {ECO:0000255}.
FT   TOPO_DOM    817    872       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    873    893       Helical. {ECO:0000255}.
FT   TOPO_DOM    894    896       Extracellular. {ECO:0000255}.
FT   TRANSMEM    897    917       Helical. {ECO:0000255}.
FT   TOPO_DOM    918    936       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    937    957       Helical. {ECO:0000255}.
FT   TOPO_DOM    958   1025       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1026   1046       Helical. {ECO:0000255}.
FT   TOPO_DOM   1047   1503       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN     1354   1498       Nudix hydrolase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00794}.
FT   MOTIF      1390   1411       Nudix box. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00794}.
FT   VAR_SEQ     538    557       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:11960981}.
FT                                /FTId=VSP_006574.
FT   VAR_SEQ     847   1503       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:12594222}.
FT                                /FTId=VSP_013018.
FT   VAR_SEQ    1291   1325       DTLEPLSTIQYNVVDGLRDRRSFHGPYTVQAGLPL -> E
FT                                (in isoform 2).
FT                                {ECO:0000303|PubMed:11960981}.
FT                                /FTId=VSP_006575.
FT   VARIANT      52     52       N -> K (in dbSNP:rs45625933).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025216.
FT   VARIANT     166    166       V -> I (in dbSNP:rs45544142).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025217.
FT   VARIANT     385    385       V -> M (in dbSNP:rs45485992).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025218.
FT   VARIANT     543    543       D -> E (in dbSNP:rs1556314).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_020032.
FT   VARIANT     780    780       D -> E (in dbSNP:rs9974927).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025219.
FT   VARIANT    1189   1189       Q -> R (in dbSNP:rs9978351).
FT                                {ECO:0000269|PubMed:11960981,
FT                                ECO:0000269|PubMed:12594222,
FT                                ECO:0000269|PubMed:15708008,
FT                                ECO:0000269|PubMed:9806837,
FT                                ECO:0000269|Ref.5}.
FT                                /FTId=VAR_025220.
FT   VARIANT    1199   1199       R -> W (in dbSNP:rs45611537).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025221.
FT   VARIANT    1201   1201       S -> G (in dbSNP:rs45519835).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025222.
FT   VARIANT    1249   1249       N -> S (in dbSNP:rs45513700).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025223.
FT   VARIANT    1347   1347       T -> M (in dbSNP:rs45589233).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025224.
FT   VARIANT    1359   1359       E -> K (in dbSNP:rs45570639).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025225.
FT   VARIANT    1368   1368       I -> M (in dbSNP:rs45613636).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025226.
FT   VARIANT    1438   1438       A -> S (in dbSNP:rs45578242).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_025227.
FT   MUTAGEN     215    215       M->A: Abolishes lowering of temperature
FT                                threshold for activation in response to
FT                                reactive oxygen species.
FT                                {ECO:0000269|PubMed:22493272}.
FT   MUTAGEN     952    952       K->A: Strongly reduces channel activity
FT                                at ph 7.3. Increased residual channel
FT                                activity after exposure to pH 5.5.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN     958    958       H->A: No effect on channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN     961    961       R->A: Mildly decreases channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN     962    962       R->A: Abolishes channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN     968    968       R->A: Abolishes channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN     973    973       H->A: No effect on channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN     995    995       H->A: Moderately decreases channel
FT                                activity. {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN    1002   1002       D->A: Strongly increased residual channel
FT                                activity after exposure to pH 5.5.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN    1005   1005       K->A: Decreases channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN    1007   1007       K->A: Nearly abolishes channel activity.
FT                                {ECO:0000269|PubMed:20660597}.
FT   MUTAGEN    1397   1397       M->I: Only slight effect on activity.
FT                                {ECO:0000269|PubMed:11804595}.
FT   MUTAGEN    1404   1404       R->Q: Abolishes channel activity.
FT                                {ECO:0000269|PubMed:15561722}.
FT   MUTAGEN    1405   1408       ILRQ->EFRE: Decreased channel activity in
FT                                response to ADP-ribose.
FT                                {ECO:0000269|PubMed:15561722}.
FT   MUTAGEN    1408   1409       QE->KK: Expected to abolish the initially
FT                                proposed hydrolase activity. Does not
FT                                abolish channel activity in response to
FT                                ADP-ribose.
FT                                {ECO:0000269|PubMed:15561722}.
FT   MUTAGEN    1408   1408       Q->E: Decreased channel activity.
FT                                {ECO:0000269|PubMed:15561722}.
FT   CONFLICT   1088   1088       S -> N (in Ref. 2; CAD01139).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1503 AA;  171198 MW;  02338437501ABFAB CRC64;
     MEPSALRKAG SEQEEGFEGL PRRVTDLGMV SNLRRSNSSL FKSWRLQCPF GNNDKQESLS
     SWIPENIKKK ECVYFVESSK LSDAGKVVCQ CGYTHEQHLE EATKPHTFQG TQWDPKKHVQ
     EMPTDAFGDI VFTGLSQKVK KYVRVSQDTP SSVIYHLMTQ HWGLDVPNLL ISVTGGAKNF
     NMKPRLKSIF RRGLVKVAQT TGAWIITGGS HTGVMKQVGE AVRDFSLSSS YKEGELITIG
     VATWGTVHRR EGLIHPTGSF PAEYILDEDG QGNLTCLDSN HSHFILVDDG THGQYGVEIP
     LRTRLEKFIS EQTKERGGVA IKIPIVCVVL EGGPGTLHTI DNATTNGTPC VVVEGSGRVA
     DVIAQVANLP VSDITISLIQ QKLSVFFQEM FETFTESRIV EWTKKIQDIV RRRQLLTVFR
     EGKDGQQDVD VAILQALLKA SRSQDHFGHE NWDHQLKLAV AWNRVDIARS EIFMDEWQWK
     PSDLHPTMTA ALISNKPEFV KLFLENGVQL KEFVTWDTLL YLYENLDPSC LFHSKLQKVL
     VEDPERPACA PAAPRLQMHH VAQVLRELLG DFTQPLYPRP RHNDRLRLLL PVPHVKLNVQ
     GVSLRSLYKR SSGHVTFTMD PIRDLLIWAI VQNRRELAGI IWAQSQDCIA AALACSKILK
     ELSKEEEDTD SSEEMLALAE EYEHRAIGVF TECYRKDEER AQKLLTRVSE AWGKTTCLQL
     ALEAKDMKFV SHGGIQAFLT KVWWGQLSVD NGLWRVTLCM LAFPLLLTGL ISFREKRLQD
     VGTPAARARA FFTAPVVVFH LNILSYFAFL CLFAYVLMVD FQPVPSWCEC AIYLWLFSLV
     CEEMRQLFYD PDECGLMKKA ALYFSDFWNK LDVGAILLFV AGLTCRLIPA TLYPGRVILS
     LDFILFCLRL MHIFTISKTL GPKIIIVKRM MKDVFFFLFL LAVWVVSFGV AKQAILIHNE
     RRVDWLFRGA VYHSYLTIFG QIPGYIDGVN FNPEHCSPNG TDPYKPKCPE SDATQQRPAF
     PEWLTVLLLC LYLLFTNILL LNLLIAMFNY TFQQVQEHTD QIWKFQRHDL IEEYHGRPAA
     PPPFILLSHL QLFIKRVVLK TPAKRHKQLK NKLEKNEEAA LLSWEIYLKE NYLQNRQFQQ
     KQRPEQKIED ISNKVDAMVD LLDLDPLKRS GSMEQRLASL EEQVAQTAQA LHWIVRTLRA
     SGFSSEADVP TLASQKAAEE PDAEPGGRKK TEEPGDSYHV NARHLLYPNC PVTRFPVPNE
     KVPWETEFLI YDPPFYTAER KDAAAMDPMG DTLEPLSTIQ YNVVDGLRDR RSFHGPYTVQ
     AGLPLNPMGR TGLRGRGSLS CFGPNHTLYP MVTRWRRNED GAICRKSIKK MLEVLVVKLP
     LSEHWALPGG SREPGEMLPR KLKRILRQEH WPSFENLLKC GMEVYKGYMD DPRNTDNAWI
     ETVAVSVHFQ DQNDVELNRL NSNLHACDSG ASIRWQVVDR RIPLYANHKT LLQKAAAEFG
     AHY
//
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