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 24-JAN-2024, entry version 203. 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, LTRPC2 GN {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 a 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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 EMDB; EMD-20478; -. DR EMDB; EMD-20479; -. DR EMDB; EMD-20480; -. DR EMDB; EMD-20482; -. DR EMDB; EMD-32082; -. DR EMDB; EMD-32083; -. DR EMDB; EMD-9132; -. DR EMDB; EMD-9133; -. DR EMDB; EMD-9134; -. DR SMR; O94759; -. DR BioGRID; 113077; 7. DR IntAct; O94759; 1. DR STRING; 9606.ENSP00000381026; -. DR BindingDB; O94759; -. DR ChEMBL; CHEMBL1250402; -. DR DrugCentral; O94759; -. DR GuidetoPHARMACOLOGY; 494; -. DR TCDB; 1.A.4.5.5; the transient receptor potential ca2+/cation channel (trp-cc) family. DR iPTMnet; O94759; -. DR PhosphoSitePlus; O94759; -. DR BioMuta; TRPM2; -. DR jPOST; O94759; -. DR MassIVE; O94759; -. DR PaxDb; 9606-ENSP00000381023; -. DR PeptideAtlas; O94759; -. DR ProteomicsDB; 50419; -. [O94759-1] DR ProteomicsDB; 50420; -. [O94759-2] DR ProteomicsDB; 50421; -. [O94759-3] DR Antibodypedia; 10236; 351 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 AGR; HGNC:12339; -. DR CTD; 7226; -. DR DisGeNET; 7226; -. DR GeneCards; TRPM2; -. DR HGNC; HGNC:12339; TRPM2. DR HPA; ENSG00000142185; Tissue enhanced (bone). 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; EFLIYEP; -. DR OrthoDB; 201873at2759; -. 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 1141 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 113 other cell types or tissues. DR ExpressionAtlas; O94759; baseline and differential. 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: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; 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: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:0005261; F:monoatomic cation channel activity; IMP: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: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:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; 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 CDD; cd03670; ADPRase_NUDT9; 1. DR Gene3D; 3.40.50.450; -; 1. DR Gene3D; 3.90.79.10; Nucleoside Triphosphate Pyrophosphohydrolase; 1. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf. DR InterPro; IPR000086; NUDIX_hydrolase_dom. DR InterPro; IPR041491; TRPM_SLOG. DR PANTHER; PTHR13800:SF2; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY M MEMBER 2; 1. DR PANTHER; PTHR13800; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 6; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF18139; LSDAT_euk; 1. DR SUPFAM; SSF55811; Nudix; 1. DR PROSITE; PS51462; NUDIX; 1. DR Genevisible; O94759; HS. 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 //