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 03-AUG-2022, entry version 195.
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}, TRPC7 {ECO:0000303|PubMed:9806837};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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) highly
RT 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 channel
RT 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of
RT 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 SUBCELLULAR
RP 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., Miller B.A.;
RT "A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell
RT 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 novel
RT N-terminal truncated protein specifically expressed in human 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; MET-385;
RP GLU-543; GLU-780; TRP-1199; GLY-1201; SER-1249; MET-1347; LYS-1359;
RP 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., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 responsive
RT element associated gene 1 (EREG1), which contains MutT like 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., Schmitz C.,
RA 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 ACTIVITY 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, ACTIVITY 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., 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 [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., Schmitz C.,
RA 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 in
RT 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 near
RT 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., 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 receptor
RT potential melastatin 2 (TRPM2) cation channel.";
RL J. Biol. Chem. 285:30091-30102(2010).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP LYS-952; HIS-958; ARG-961; ARG-962; ARG-968; HIS-973; HIS-995; ASP-1002;
RP 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., 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 [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., 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 [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 reveals
RT novel direct agonist ADP-ribose-2'-phosphate.";
RL J. Gen. Physiol. 145:419-430(2015).
RN [22]
RP FUNCTION, AND MUTAGENESIS OF ARG-1400 AND ARG-1407.
RX PubMed=25620041; DOI=10.1038/srep08032;
RA Kuehn F.J., Kuehn C., Lueckhoff A.;
RT "Functional characterisation of a TRPM2 orthologue from the sea anemone
RT Nematostella vectensis in human cells.";
RL Sci. Rep. 5:8032-8032(2015).
RN [23]
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 does
RT not possess ADP ribose hydrolase activity.";
RL Elife 5:0-0(2016).
RN [24]
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 migration
RT by Ca2+ and Zn2+: role of TRPM2 channels.";
RL J. Cell Sci. 129:2016-2029(2016).
RN [25]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=28775320; DOI=10.1038/s41598-017-07652-4;
RA Kuehn F.J.P., Mathis W., Cornelia K., Hoffmann D.C., Lueckhoff A.;
RT "Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of
RT an archetypal TRPM channel from Nematostella vectensis.";
RL Sci. Rep. 7:7245-7245(2017).
RN [26]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF 984-GLY-TYR-985.
RX PubMed=29745897; DOI=10.7554/elife.36409;
RA Zhang Z., Toth B., Szollosi A., Chen J., Csanady L.;
RT "Structure of a TRPM2 channel in complex with Ca2+ explains unique gating
RT regulation.";
RL Elife 7:0-0(2018).
RN [27]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF APOPROTEIN AND IN
RP COMPLEX WITH ADP-RIBOSE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, DOMAIN,
RP AND MUTAGENESIS OF ARG-302; ARG-358 AND 1228-ARG--TYR-1503.
RX PubMed=30467180; DOI=10.1126/science.aav4809;
RA Wang L., Fu T.M., Zhou Y., Xia S., Greka A., Wu H.;
RT "Structures and gating mechanism of human TRPM2.";
RL Science 362:0-0(2018).
CC -!- FUNCTION: [Isoform 1]: Nonselective, voltage-independent cation channel
CC that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic
CC Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575,
CC PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673,
CC PubMed:19171771, PubMed:20660597, PubMed:25620041, PubMed:27383051,
CC PubMed:27068538, PubMed:28775320, PubMed:29745897, PubMed:30467180).
CC Functions as ligand-gated ion channel (PubMed:19171771,
CC PubMed:25620041, PubMed:28775320, PubMed:30467180). Binding of ADP-
CC ribose to the cytoplasmic Nudix domain causes a conformation change;
CC the channel is primed but still requires Ca(2+) binding to trigger
CC channel opening (PubMed:19171771, PubMed:25620041, PubMed:28775320,
CC PubMed:29745897, PubMed:30467180). Extracellular calcium passes through
CC the channel and increases channel activity (PubMed:19171771).
CC Contributes to Ca(2+) release from intracellular stores in response to
CC ADP-ribose (PubMed:19454650). Plays a role in numerous processes that
CC involve signaling via intracellular Ca(2+) levels (Probable). Besides,
CC mediates the release of lysosomal Zn(2+) stores in response to reactive
CC oxygen species, leading to increased cytosolic Zn(2+) levels
CC (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to
CC 40 degrees Celsius) (PubMed:16601673). 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:11960981,
CC PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722,
CC PubMed:16601673, PubMed:19171771, PubMed:25620041, PubMed:27383051,
CC PubMed:27068538, PubMed:30467180). The precise physiological activators
CC are under debate; the true, physiological activators may be ADP-ribose
CC and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360).
CC Activation by ADP-ribose and beta-NAD is strongly increased by moderate
CC heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive
CC oxygen species lower the threshold for activation by moderate heat (37
CC degrees Celsius) (PubMed:22493272). Plays a role in mediating
CC behavorial and physiological responses to moderate heat and thereby
CC contributes to body temperature homeostasis. Plays a role in insulin
CC secretion, a process that requires increased cytoplasmic Ca(2+) levels
CC (By similarity). Required for normal IFNG and cytokine secretion and
CC normal innate immune immunity in response to bacterial infection.
CC Required for normal phagocytosis and cytokine release by macrophages
CC exposed to zymosan (in vitro). 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 (By similarity). Plays
CC 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 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:25620041, ECO:0000269|PubMed:25918360,
CC ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051,
CC ECO:0000269|PubMed:28775320, ECO:0000269|PubMed:29745897,
CC ECO:0000269|PubMed:30467180, ECO:0000305}.
CC -!- FUNCTION: [Isoform 2]: Lacks cation channel activity. Does not mediate
CC cation transport in response to oxidative stress or ADP-ribose.
CC {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 -!- ACTIVITY REGULATION: Inactivated by exposure to extracellular pH
CC between 4.0 and 6.5; irreversibly inactivated when open channels are
CC exposed to extracellular pH between 4.0 and 6.5, while pre-exposure of
CC closed channels to extracellular pH 5.5 gives rise to currents that
CC rapidly inactivate, but protects against irreversible inactivation
CC (PubMed:20660597). Inactivated by intracellular ATP (PubMed:11509734).
CC Activated by arachidonic acid (PubMed:11804595). Inhibited by 2-
CC aminoethyl diphenylborinate (2-APB) (PubMed:28775320).
CC {ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595,
CC ECO:0000269|PubMed:20660597, ECO:0000269|PubMed:28775320}.
CC -!- SUBUNIT: Homotetramer (PubMed:30467180). Isoform 1 can interact with
CC isoform 3. This interaction decreases calcium influx through isoform 1
CC and suppresses susceptibility to oxidative stress-induced cell death.
CC {ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:30467180}.
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,
CC ECO:0000269|PubMed:30467180}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:30467180}. Perikaryon
CC {ECO:0000250|UniProtKB:E9PTA2}. Cell projection
CC {ECO:0000250|UniProtKB:E9PTA2}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:E9PTA2}. Lysosome {ECO:0000269|PubMed:27068538}.
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. Detected on cytoplasmic vesicles and lysosomes in immature
CC bone marrow dendritic cells (By similarity).
CC {ECO:0000250|UniProtKB:E9PTA2, ECO:0000250|UniProtKB:Q91YD4}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222}; Multi-pass
CC 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 granulocytes.
CC {ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:11509734}.
CC -!- DOMAIN: The cytosolic nudix box binds ADP-ribose and is required for
CC channel activation by ADP-ribose (PubMed:15561722, PubMed:16601673,
CC PubMed:30467180). {ECO:0000269|PubMed:15561722,
CC ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:30467180}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC 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 that
CC the nudix hydrolase domain lacks enzyme activity and suggests that
CC spontaneous degradation of the substrate underlies the previously
CC reported low activity (PubMed:27383051). {ECO:0000269|PubMed:11385575,
CC ECO:0000269|PubMed:27383051}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB64300.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/trpm2/";
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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. [O94759-1]
DR RefSeq; XP_005261228.1; XM_005261171.3. [O94759-1]
DR PDB; 6MIX; EM; 3.60 A; A/B/C/D=1-1503.
DR PDB; 6MIZ; EM; 6.10 A; A/B/C/D=1-1503.
DR PDB; 6MJ2; EM; 6.36 A; A/B/C/D=1-1503.
DR PDB; 6PUO; EM; 3.30 A; A/B/C/D=1-1503.
DR PDB; 6PUR; EM; 4.40 A; A/B/C/D=1-1503.
DR PDB; 6PUS; EM; 3.70 A; A/B/C/D=1-1503.
DR PDB; 6PUU; EM; 3.70 A; A/B/C/D=1-1503.
DR PDB; 7VQ1; EM; 3.76 A; A/B/C/D=1-1503.
DR PDB; 7VQ2; EM; 3.68 A; A/B/C/D=745-1098.
DR PDBsum; 6MIX; -.
DR PDBsum; 6MIZ; -.
DR PDBsum; 6MJ2; -.
DR PDBsum; 6PUO; -.
DR PDBsum; 6PUR; -.
DR PDBsum; 6PUS; -.
DR PDBsum; 6PUU; -.
DR PDBsum; 7VQ1; -.
DR PDBsum; 7VQ2; -.
DR AlphaFoldDB; O94759; -.
DR SMR; O94759; -.
DR BioGRID; 113077; 4.
DR IntAct; O94759; 1.
DR STRING; 9606.ENSP00000381023; -.
DR BindingDB; O94759; -.
DR ChEMBL; CHEMBL1250402; -.
DR DrugCentral; O94759; -.
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 jPOST; O94759; -.
DR MassIVE; O94759; -.
DR PaxDb; O94759; -.
DR PeptideAtlas; O94759; -.
DR PRIDE; O94759; -.
DR ProteomicsDB; 50419; -. [O94759-1]
DR ProteomicsDB; 50420; -. [O94759-2]
DR ProteomicsDB; 50421; -. [O94759-3]
DR Antibodypedia; 10236; 311 antibodies from 32 providers.
DR DNASU; 7226; -.
DR Ensembl; ENST00000300481.13; ENSP00000300481.9; ENSG00000142185.18. [O94759-2]
DR Ensembl; ENST00000300482.9; ENSP00000300482.5; ENSG00000142185.18. [O94759-1]
DR Ensembl; ENST00000397928.6; ENSP00000381023.1; ENSG00000142185.18. [O94759-1]
DR GeneID; 7226; -.
DR KEGG; hsa:7226; -.
DR MANE-Select; ENST00000397928.6; ENSP00000381023.1; NM_003307.4; NP_003298.2.
DR UCSC; uc002zet.1; human. [O94759-1]
DR CTD; 7226; -.
DR DisGeNET; 7226; -.
DR GeneCards; TRPM2; -.
DR HGNC; HGNC:12339; TRPM2.
DR HPA; ENSG00000142185; Tissue enhanced (bone marrow, brain, lymphoid tissue).
DR MIM; 603749; gene.
DR neXtProt; NX_O94759; -.
DR OpenTargets; ENSG00000142185; -.
DR PharmGKB; PA37012; -.
DR VEuPathDB; HostDB:ENSG00000142185; -.
DR eggNOG; KOG3614; Eukaryota.
DR eggNOG; KOG4195; Eukaryota.
DR GeneTree; ENSGT00940000156404; -.
DR HOGENOM; CLU_001390_0_2_1; -.
DR InParanoid; O94759; -.
DR OMA; DGTHGHY; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; O94759; -.
DR TreeFam; TF314204; -.
DR PathwayCommons; O94759; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SABIO-RK; O94759; -.
DR SignaLink; O94759; -.
DR BioGRID-ORCS; 7226; 15 hits in 1061 CRISPR screens.
DR ChiTaRS; TRPM2; human.
DR GeneWiki; TRPM2; -.
DR GenomeRNAi; 7226; -.
DR Pharos; O94759; Tchem.
DR PRO; PR:O94759; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; O94759; protein.
DR Bgee; ENSG00000142185; Expressed in right frontal lobe and 112 other tissues.
DR ExpressionAtlas; O94759; baseline and differential.
DR Genevisible; O94759; HS.
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; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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; IDA: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:0005384; F:manganese ion transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0072571; F:mono-ADP-D-ribose binding; 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; IDA:UniProtKB.
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:0098655; P:cation transmembrane transport; IBA:GO_Central.
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:0044849; P:estrous cycle; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
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:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0033194; P:response to hydroperoxide; IEA:Ensembl.
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 ion transmembrane transport; IMP: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 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Disulfide bond; Ion channel; Ion transport; Lysosome; Membrane;
KW Metal-binding; Reference proteome; Sodium; Sodium channel;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1503
FT /note="Transient receptor potential cation channel
FT subfamily M member 2"
FT /id="PRO_0000215326"
FT TOPO_DOM 1..752
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 753..769
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 770..795
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 796..816
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 817..827
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 828..848
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 849..867
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 868..888
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 889..896
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 897..917
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 918..929
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 930..950
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 951..970
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 971..985
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 986..1022
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1023..1044
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 1045..1079
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 1080..1098
FT /evidence="ECO:0000269|PubMed:30467180"
FT TOPO_DOM 1099..1503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 1354..1498
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1206..1237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1390..1411
FT /note="Nudix box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT COMPBIAS 1221..1237
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 843
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30467180"
FT BINDING 846
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30467180"
FT BINDING 869
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30467180"
FT BINDING 1073
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:30467180"
FT DISULFID 996..1008
FT /evidence="ECO:0000250|UniProtKB:A0A0R4IMY7"
FT VAR_SEQ 538..557
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11960981"
FT /id="VSP_006574"
FT VAR_SEQ 847..1503
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12594222"
FT /id="VSP_013018"
FT VAR_SEQ 1291..1325
FT /note="DTLEPLSTIQYNVVDGLRDRRSFHGPYTVQAGLPL -> E (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:11960981"
FT /id="VSP_006575"
FT VARIANT 52
FT /note="N -> K (in dbSNP:rs45625933)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025216"
FT VARIANT 166
FT /note="V -> I (in dbSNP:rs45544142)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025217"
FT VARIANT 385
FT /note="V -> M (in dbSNP:rs45485992)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025218"
FT VARIANT 543
FT /note="D -> E (in dbSNP:rs1556314)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020032"
FT VARIANT 780
FT /note="D -> E (in dbSNP:rs9974927)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025219"
FT VARIANT 1189
FT /note="Q -> R (in dbSNP:rs9978351)"
FT /evidence="ECO:0000269|PubMed:11960981,
FT ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:15708008,
FT ECO:0000269|PubMed:9806837, ECO:0000269|Ref.5"
FT /id="VAR_025220"
FT VARIANT 1199
FT /note="R -> W (in dbSNP:rs45611537)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025221"
FT VARIANT 1201
FT /note="S -> G (in dbSNP:rs45519835)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025222"
FT VARIANT 1249
FT /note="N -> S (in dbSNP:rs45513700)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025223"
FT VARIANT 1347
FT /note="T -> M (in dbSNP:rs45589233)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025224"
FT VARIANT 1359
FT /note="E -> K (in dbSNP:rs45570639)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025225"
FT VARIANT 1368
FT /note="I -> M (in dbSNP:rs45613636)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025226"
FT VARIANT 1438
FT /note="A -> S (in dbSNP:rs45578242)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_025227"
FT MUTAGEN 215
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 MUTAGEN 302
FT /note="R->A: No significant effect on channel activity;
FT when associated with A-358."
FT /evidence="ECO:0000269|PubMed:30467180"
FT MUTAGEN 358
FT /note="R->A: No significant effect on channel activity;
FT when associated with A-302."
FT /evidence="ECO:0000269|PubMed:30467180"
FT MUTAGEN 952
FT /note="K->A: Strongly reduces channel activity at ph 7.3.
FT Increased residual channel activity after exposure to pH
FT 5.5."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 958
FT /note="H->A: No effect on channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 961
FT /note="R->A: Mildly decreases channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 962
FT /note="R->A: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 968
FT /note="R->A: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 973
FT /note="H->A: No effect on channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 984..985
FT /note="GY->LDE: Prevents fast inactivation of the channel."
FT /evidence="ECO:0000269|PubMed:29745897"
FT MUTAGEN 995
FT /note="H->A: Moderately decreases channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 1002
FT /note="D->A: Strongly increased residual channel activity
FT after exposure to pH 5.5."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 1005
FT /note="K->A: Decreases channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 1007
FT /note="K->A: Nearly abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:20660597"
FT MUTAGEN 1228..1503
FT /note="Missing: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:30467180"
FT MUTAGEN 1397
FT /note="M->I: Only slight effect on activity."
FT /evidence="ECO:0000269|PubMed:11804595"
FT MUTAGEN 1400
FT /note="R->Q: No effect on channel activity; when associated
FT with G-1407."
FT /evidence="ECO:0000269|PubMed:25620041"
FT MUTAGEN 1404
FT /note="R->Q: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:15561722"
FT MUTAGEN 1405..1408
FT /note="ILRQ->EFRE: Decreased channel activity in response
FT to ADP-ribose."
FT /evidence="ECO:0000269|PubMed:15561722"
FT MUTAGEN 1407
FT /note="R->G: No effect on channel activity; when associated
FT with Q-1400."
FT /evidence="ECO:0000269|PubMed:25620041"
FT MUTAGEN 1408..1409
FT /note="QE->KK: Expected to abolish the initially proposed
FT hydrolase activity. Does not abolish channel activity in
FT response to ADP-ribose."
FT /evidence="ECO:0000269|PubMed:15561722"
FT MUTAGEN 1408
FT /note="Q->E: Decreased channel activity."
FT /evidence="ECO:0000269|PubMed:15561722"
FT CONFLICT 1088
FT /note="S -> N (in Ref. 2; CAD01139)"
FT /evidence="ECO:0000305"
FT HELIX 57..66
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 151..160
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 168..174
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 184..201
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 214..228
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 334..345
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 360..366
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 376..386
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 399..411
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 421..423
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 430..442
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 450..461
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 466..470
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 481..484
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 485..493
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 497..505
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 510..513
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 516..522
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 531..541
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 545..549
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 558..569
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 621..630
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 631..633
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 635..641
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 642..644
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 648..662
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 669..696
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 699..702
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 703..705
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 707..709
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 710..713
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 714..716
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 717..723
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 727..730
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 734..744
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 753..761
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 764..769
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 777..780
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 784..793
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 795..818
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 827..847
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 856..864
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 867..887
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 889..891
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 892..907
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 908..915
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 918..920
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 921..955
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 963..965
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 966..979
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1021..1035
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1036..1038
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1039..1055
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1056..1058
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1059..1076
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1082..1085
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1086..1097
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1107..1109
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1115..1141
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1144..1164
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1240..1242
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1259..1261
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1275..1277
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1279..1281
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1282..1286
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1289..1291
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1301..1303
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1334..1337
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1339..1343
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1346..1355
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1359..1361
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1367..1370
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1372..1378
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1380..1382
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1383..1386
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1393..1397
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1398..1403
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1404..1407
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1410..1418
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1422..1429
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1436..1438
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1440..1449
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1452..1454
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1456..1462
FT /evidence="ECO:0007829|PDB:6PUO"
FT STRAND 1471..1477
FT /evidence="ECO:0007829|PDB:6PUO"
FT HELIX 1488..1495
FT /evidence="ECO:0007829|PDB:6PUO"
FT TURN 1496..1500
FT /evidence="ECO:0007829|PDB:6PUO"
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
