ID AT2A2_HUMAN Reviewed; 1042 AA. AC P16615; A6NDN7; B4DF05; P16614; Q86VJ2; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 27-MAR-2024, entry version 253. DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 {ECO:0000305}; DE Short=SERCA2; DE Short=SR Ca(2+)-ATPase 2; DE EC=7.2.2.10 {ECO:0000269|PubMed:28890335}; DE AltName: Full=Calcium pump 2; DE AltName: Full=Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform; DE AltName: Full=Endoplasmic reticulum class 1/2 Ca(2+) ATPase; GN Name=ATP2A2 {ECO:0000312|HGNC:HGNC:812}; Synonyms=ATP2B; 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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Kidney; RX PubMed=2844796; DOI=10.1016/s0021-9258(18)68141-4; RA Lytton J., Maclennan D.H.; RT "Molecular cloning of cDNAs from human kidney coding for two alternatively RT spliced products of the cardiac Ca2+-ATPase gene."; RL J. Biol. Chem. 263:15024-15031(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-1042 (ISOFORM 4). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 954-1042 (ISOFORM 3), AND TISSUE SPECIFICITY. RX PubMed=12659872; DOI=10.1016/s0006-291x(03)00405-4; RA Gelebart P., Martin V., Enouf J., Papp B.; RT "Identification of a new SERCA2 splice variant regulated during monocytic RT differentiation."; RL Biochem. Biophys. Res. Commun. 303:676-684(2003). RN [6] RP INTERACTION WITH S100A1, AND SUBCELLULAR LOCATION. RX PubMed=12804600; DOI=10.1016/s0006-291x(03)00987-2; RA Kiewitz R., Acklin C., Schaefer B.W., Maco B., Uhrik B., Wuytack F., RA Erne P., Heizmann C.W.; RT "Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+ RT -ATPase2a and phospholamban in the human heart."; RL Biochem. Biophys. Res. Commun. 306:550-557(2003). RN [7] RP INTERACTION WITH TRAM2. RX PubMed=14749390; DOI=10.1128/mcb.24.4.1758-1768.2004; RA Stefanovic B., Stefanovic L., Schnabl B., Bataller R., Brenner D.A.; RT "TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and RT is necessary for collagen type I synthesis."; RL Mol. Cell. Biol. 24:1758-1768(2004). RN [8] RP NITRATION AT TYR-294 AND TYR-295. RX PubMed=16399855; DOI=10.1152/ajpheart.01293.2005; RA Xu S., Ying J., Jiang B., Guo W., Adachi T., Sharov V., Lazar H., RA Menzoian J., Knyushko T.V., Bigelow D., Schoeneich C., Cohen R.A.; RT "Detection of sequence-specific tyrosine nitration of manganese SOD and RT SERCA in cardiovascular disease and aging."; RL Am. J. Physiol. 290:H2220-H2227(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP INTERACTION WITH HAX1. RX PubMed=18971376; DOI=10.1091/mbc.e08-06-0587; RA Vafiadaki E., Arvanitis D.A., Pagakis S.N., Papalouka V., Sanoudou D., RA Kontrogianni-Konstantopoulos A., Kranias E.G.; RT "The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its RT protein levels to promote cell survival."; RL Mol. Biol. Cell 20:306-318(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP INTERACTION WITH SLC35G1 AND STIM1. RX PubMed=22084111; DOI=10.1073/pnas.1117231108; RA Krapivinsky G., Krapivinsky L., Stotz S.C., Manasian Y., Clapham D.E.; RT "POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to RT multiple transporters."; RL Proc. Natl. Acad. Sci. U.S.A. 108:19234-19239(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-580 AND SER-663, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP INTERACTION WITH TMEM203. RX PubMed=25996873; DOI=10.1371/journal.pone.0127480; RA Shambharkar P.B., Bittinger M., Latario B., Xiong Z., Bandyopadhyay S., RA Davis V., Lin V., Yang Y., Valdez R., Labow M.A.; RT "TMEM203 is a novel regulator of intracellular calcium homeostasis and is RT required for spermatogenesis."; RL PLoS ONE 10:E0127480-E0127480(2015). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [20] RP INTERACTION WITH TMX1. RX PubMed=27502484; DOI=10.1083/jcb.201512077; RA Raturi A., Gutierrez T., Ortiz-Sandoval C., Ruangkittisakul A., RA Herrera-Cruz M.S., Rockley J.P., Gesson K., Ourdev D., Lou P.H., RA Lucchinetti E., Tahbaz N., Zaugg M., Baksh S., Ballanyi K., Simmen T.; RT "TMX1 determines cancer cell metabolism as a thiol-based modulator of ER- RT mitochondria Ca2+ flux."; RL J. Cell Biol. 214:433-444(2016). RN [21] RP VARIANTS DD. RX PubMed=10441323; DOI=10.1093/hmg/8.9.1611; RA Sakuntabhai A., Burge S., Monk S., Hovnanian A.; RT "Spectrum of novel ATP2A2 mutations in patients with Darier's disease."; RL Hum. Mol. Genet. 8:1611-1619(1999). RN [22] RP VARIANTS DD, AND TISSUE SPECIFICITY. RX PubMed=10441324; DOI=10.1093/hmg/8.9.1621; RA Ruiz-Perez V.L., Carter S.A., Healy E., Todd C., Rees J.L., Steijlen P.M., RA Carmichael A.J., Lewis H.M., Hohl D., Itin P., Vahlquist A., Gobello T., RA Mazzanti C., Reggazini R., Nagy G., Munro C.S., Strachan T.; RT "ATP2A2 mutations in Darier's disease: variant cutaneous phenotypes are RT associated with missense mutations, but neuropsychiatric features are RT independent of mutation class."; RL Hum. Mol. Genet. 8:1621-1630(1999). RN [23] RP VARIANTS DD THR-39; ARG-560 AND LEU-765. RX PubMed=10441325; DOI=10.1093/hmg/8.9.1631; RA Jacobsen N.J.O., Lyons I., Hoogendoorn B., Burge S., Kwok P.-Y., RA O'Donovan M.C., Craddock N., Owen M.J.; RT "ATP2A2 mutations in Darier's disease and their relationship to RT neuropsychiatric phenotypes."; RL Hum. Mol. Genet. 8:1631-1636(1999). RN [24] RP VARIANTS DD GLU-23; LYS-357; PHE-495 AND ARG-749. RX PubMed=10080178; DOI=10.1038/6784; RA Sakuntabhai A., Ruiz-Perez V., Carter S., Jacobsen N., Burge S., Monk S., RA Smith M., Munro C.S., O'Donovan M.C., Craddock N., Kucherlapati R., RA Rees J.L., Owen M.J., Lathrop G.M., Monaco A.P., Strachan T., Hovnanian A.; RT "Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease."; RL Nat. Genet. 21:271-277(1999). RN [25] RP VARIANT AKV LEU-602, CHARACTERIZATION OF VARIANT AKV LEU-602, AND FUNCTION. RX PubMed=12542527; DOI=10.1046/j.1523-1747.2003.t01-1-12045.x; RA Dhitavat J., Macfarlane S., Dode L., Leslie N., Sakuntabhai A., RA MacSween R., Saihan E., Hovnanian A.; RT "Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: RT evidence that it is allelic to Darier's disease."; RL J. Invest. Dermatol. 120:229-232(2003). RN [26] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=16402920; DOI=10.1042/bj20051427; RA Dally S., Bredoux R., Corvazier E., Andersen J.P., Clausen J.D., Dode L., RA Fanchaouy M., Gelebart P., Monceau V., Del Monte F., Gwathmey J.K., RA Hajjar R., Chaabane C., Bobe R., Raies A., Enouf J.; RT "Ca2+-ATPases in non-failing and failing heart: evidence for a novel RT cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c)."; RL Biochem. J. 395:249-258(2006). RN [27] RP FUNCTION, INTERACTION WITH SLN; PLN; VMP1 AND ULK1, CATALYTIC ACTIVITY, RP MUTAGENESIS OF PHE-256, AND ACTIVITY REGULATION. RX PubMed=28890335; DOI=10.1016/j.molcel.2017.08.005; RA Zhao Y.G., Chen Y., Miao G., Zhao H., Qu W., Li D., Wang Z., Liu N., Li L., RA Chen S., Liu P., Feng D., Zhang H.; RT "The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity RT to Control ER-Isolation Membrane Contacts for Autophagosome Formation."; RL Mol. Cell 67:974.e6-989.e6(2017). RN [28] RP INTERACTION WITH TMX2. RX PubMed=31735293; DOI=10.1016/j.ajhg.2019.10.009; RA Vandervore L.V., Schot R., Milanese C., Smits D.J., Kasteleijn E., RA Fry A.E., Pilz D.T., Brock S., Boerklue-Yuecel E., Post M., RA Bahi-Buisson N., Sanchez-Soler M.J., van Slegtenhorst M., Keren B., RA Afenjar A., Coury S.A., Tan W.H., Oegema R., de Vries L.S., Fawcett K.A., RA Nikkels P.G.J., Bertoli-Avella A., Al Hashem A., Alwabel A.A., RA Tlili-Graiess K., Efthymiou S., Zafar F., Rana N., Bibi F., Houlden H., RA Maroofian R., Person R.E., Crunk A., Savatt J.M., Turner L., Doosti M., RA Karimiani E.G., Saadi N.W., Akhondian J., Lequin M.H., Kayserili H., RA van der Spek P.J., Jansen A.C., Kros J.M., Verdijk R.M., Milosevic N.J., RA Fornerod M., Mastroberardino P.G., Mancini G.M.S.; RT "TMX2 is a crucial regulator of cellular redox state, and its dysfunction RT causes severe brain developmental abnormalities."; RL Am. J. Hum. Genet. 105:1126-1147(2019). RN [29] RP VARIANT DD LEU-41 DEL. RX PubMed=19995371; DOI=10.1111/j.1365-2133.2009.09580.x; RA Tsuruta D., Akiyama M., Ishida-Yamamoto A., Imanishi H., Mizuno N., RA Sowa J., Kobayashi H., Ishii M., Kurokawa I., Shimizu H.; RT "Three-base deletion mutation c.120_122delGTT in ATP2A2 leads to the unique RT phenotype of comedonal Darier disease."; RL Br. J. Dermatol. 162:687-689(2010). RN [30] RP VARIANTS DD 74-VAL--GLN-108 DEL; SER-101; GLN-131; 194-VAL--PRO-197 DEL; RP PRO-590; ALA-625; GLU-626; 666-ARG--SER-1042 DEL; PRO-672; PRO-691; RP TRP-750; TRP-765; GLY-849 INS; PRO-900 AND ARG-943. RX PubMed=28035777; DOI=10.1002/humu.23164; RG European Professional Contributors; RA Nellen R.G., Steijlen P.M., van Steensel M.A., Vreeburg M., Frank J., RA van Geel M.; RT "Mendelian Disorders of Cornification Caused by Defects in Intracellular RT Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and RT ATP2C1 associated with Darier disease and Hailey-Hailey disease."; RL Hum. Mutat. 38:343-356(2017). CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of CC ATP coupled with the translocation of calcium from the cytosol to the CC sarcoplasmic reticulum lumen (PubMed:16402920, PubMed:12542527). CC Involved in autophagy in response to starvation. Upon interaction with CC VMP1 and activation, controls ER-isolation membrane contacts for CC autophagosome formation (PubMed:28890335). Also modulates ER contacts CC with lipid droplets, mitochondria and endosomes (PubMed:28890335). In CC coordination with FLVCR2 mediates heme-stimulated switching from CC mitochondrial ATP synthesis to thermogenesis (By similarity). CC {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, CC ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}. CC -!- FUNCTION: [Isoform 2]: Involved in the regulation of the CC contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated CC Ca(2+) signaling pathways via its interaction with TMEM64 which is CC critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS CC generation necessary for proper osteoclast generation. Association CC between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking CC for activation of NFATC1 and production of mitochondrial ROS, thereby CC triggering Ca(2+) signaling cascades that promote osteoclast CC differentiation and activation. {ECO:0000250|UniProtKB:O55143}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate; CC Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:456216; EC=7.2.2.10; CC Evidence={ECO:0000269|PubMed:28890335}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; CC Evidence={ECO:0000269|PubMed:28890335}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P11607}; CC -!- ACTIVITY REGULATION: Has different conformational states with CC differential Ca2+ affinity. The E1 conformational state (active form) CC shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) CC affinity. Reversibly inhibited by phospholamban (PLN) at low calcium CC concentrations. Inhibited by sarcolipin (SLN) and myoregulin (MRLN). CC The inhibition is blocked by VMP1 (PubMed:28890335). Enhanced by DWORF; CC DWORF increases activity by displacing sarcolipin (SLN), phospholamban CC (PLN) and myoregulin (MRLN) (By similarity). Stabilizes SERCA2 in its CC E2 state (PubMed:28890335). {ECO:0000250|UniProtKB:O55143, CC ECO:0000250|UniProtKB:P04191, ECO:0000250|UniProtKB:Q8R429, CC ECO:0000269|PubMed:28890335}. CC -!- SUBUNIT: Interacts with sarcolipin (SLN); the interaction inhibits CC ATP2A2 Ca(2+) affinity (PubMed:28890335). Interacts with phospholamban CC (PLN); the interaction inhibits ATP2A2 Ca(2+) affinity CC (PubMed:28890335). Interacts with myoregulin (MRLN) (By similarity). CC Interacts with DWORF (By similarity). Interacts with HAX1 CC (PubMed:18971376). Interacts with S100A8 and S100A9 (By similarity). CC Interacts with SLC35G1 and STIM1 (PubMed:22084111). Interacts with CC TMEM203 (PubMed:25996873). Interacts with TMEM64 and PDIA3 (By CC similarity). Interacts with TMX1 (PubMed:27502484). Interacts with TMX2 CC (PubMed:31735293). Interacts with VMP1; VMP1 competes with PLN and SLN CC to prevent them from forming an inhibitory complex with ATP2A2 CC (PubMed:28890335). Interacts with ULK1 (PubMed:28890335). Interacts CC with S100A1 in a Ca(2+)-dependent manner (PubMed:12804600). Interacts CC with TUNAR (By similarity). Interacts with FLVCR2; this interaction CC occurs in the absence of heme and promotes ATP2A2 proteasomal CC degradation; this complex is dissociated upon heme binding (By CC similarity). Interacts with FNIP1 (By similarity). CC {ECO:0000250|UniProtKB:O55143, ECO:0000250|UniProtKB:P04191, CC ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:12804600, CC ECO:0000269|PubMed:14749390, ECO:0000269|PubMed:18971376, CC ECO:0000269|PubMed:22084111, ECO:0000269|PubMed:25996873, CC ECO:0000269|PubMed:27502484, ECO:0000269|PubMed:28890335, CC ECO:0000269|PubMed:31735293}. CC -!- SUBUNIT: [Isoform 1]: Interacts with TRAM2 (via C-terminus). CC {ECO:0000269|PubMed:14749390}. CC -!- INTERACTION: CC P16615; P55085: F2RL1; NbExp=2; IntAct=EBI-358933, EBI-4303189; CC P16615; P41143: OPRD1; NbExp=3; IntAct=EBI-358933, EBI-2624456; CC P16615; O76024: WFS1; NbExp=3; IntAct=EBI-358933, EBI-720609; CC P16615-1; P13569: CFTR; NbExp=6; IntAct=EBI-11613988, EBI-349854; CC P16615-1; E2JF22: Piezo1; Xeno; NbExp=2; IntAct=EBI-11613988, EBI-9837938; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:O55143}; Multi-pass membrane protein CC {ECO:0000255}. Sarcoplasmic reticulum membrane CC {ECO:0000269|PubMed:12804600}; Multi-pass membrane protein CC {ECO:0000255}. Note=Colocalizes with FLVCR2 at the mitochondrial-ER CC contact junction. {ECO:0000250|UniProtKB:O55143}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=SERCA2 transcripts differ only in their 3'-UTR region and are CC expressed in a tissue-specific manner.; CC Name=1; Synonyms=ATP2A2B, Class 2-4, HK1, SERCA2b; CC IsoId=P16615-1; Sequence=Displayed; CC Name=2; Synonyms=ATP2A2A, Class 1, HK2, SERCA2a; CC IsoId=P16615-2; Sequence=VSP_000358; CC Name=3; Synonyms=SERCA2C; CC IsoId=P16615-3; Sequence=VSP_039393; CC Name=4; CC IsoId=P16615-4; Sequence=VSP_039392; CC Name=5; CC IsoId=P16615-5; Sequence=VSP_039394; CC -!- TISSUE SPECIFICITY: Isoform 1 is widely expressed in smooth muscle and CC nonmuscle tissues such as in adult skin epidermis, with highest CC expression in liver, pancreas and lung, and intermediate expression in CC brain, kidney and placenta. Also expressed at lower levels in heart and CC skeletal muscle. Isoforms 2 and 3 are highly expressed in the heart and CC slow twitch skeletal muscle. Expression of isoform 3 is predominantly CC restricted to cardiomyocytes and in close proximity to the sarcolemma. CC Both isoforms are mildly expressed in lung, kidney, liver, pancreas and CC placenta. Expression of isoform 3 is amplified during monocytic CC differentiation and also observed in the fetal heart. CC {ECO:0000269|PubMed:10441324, ECO:0000269|PubMed:12659872, CC ECO:0000269|PubMed:16402920}. CC -!- DOMAIN: Ca(2+) and ATP binding cause major rearrangements of the CC cytoplasmic and transmembrane domains. According to the E1-E2 model, CC Ca(2+) binding to the cytosolic domain of the pump in the high-affinity CC E1 conformation is followed by the ATP-dependent phosphorylation of the CC active site Asp, giving rise to E1P. A conformational change of the CC phosphoenzyme gives rise to the low-affinity E2P state that exposes the CC Ca(2+) ions to the lumenal side and promotes Ca(2+) release. CC Dephosphorylation of the active site Asp mediates the subsequent return CC to the E1 conformation. {ECO:0000250|UniProtKB:P04191}. CC -!- DOMAIN: PLN and SLN both have a single transmembrane helix; both occupy CC a similar binding site that is situated between the ATP2A2 CC transmembrane helices. {ECO:0000250|UniProtKB:P04191}. CC -!- PTM: Nitrated under oxidative stress. Nitration on the two tyrosine CC residues inhibits catalytic activity. {ECO:0000269|PubMed:16399855}. CC -!- PTM: Serotonylated on Gln residues by TGM2 in response to hypoxia, CC leading to its inactivation. {ECO:0000250|UniProtKB:O55143}. CC -!- DISEASE: Acrokeratosis verruciformis (AKV) [MIM:101900]: A localized CC disorder of keratinization, which is inherited as an autosomal dominant CC trait. Its onset is early in life with multiple flat-topped, flesh- CC colored papules on the hands and feet, punctate keratoses on the palms CC and soles, with varying degrees of nail involvement. The histopathology CC shows a distinctive pattern of epidermal features with hyperkeratosis, CC hypergranulosis and acanthosis together with papillomatosis. These CC changes are frequently associated with circumscribed elevations of the CC epidermis that are said to resemble church spires. There are no CC features of dyskeratosis or acantholysis, the typical findings in CC lesions of Darier disease. {ECO:0000269|PubMed:12542527}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Darier disease (DD) [MIM:124200]: A skin disorder CC characterized by warty papules and plaques in seborrheic areas (central CC trunk, flexures, scalp and forehead), palmoplantar pits and distinctive CC nail abnormalities. It is due to loss of adhesion between epidermal CC cells (acantholysis) and abnormal keratinization. Patients with mild CC disease may have no more than a few scattered keratotic papules or CC subtle nail changes, whereas those with severe disease are handicapped CC by widespread malodorous keratotic plaques. Some patients present with CC hemorrhage into acantholytic vesicles on the palms and dorsal aspects CC of the fingers which gives rise to black macules. In a few families CC affected by Darier disease, neuropsychiatric abnormalities such as mild CC intellectual disability, schizophrenia, bipolar disorder and epilepsy CC have been reported. Stress, UV exposure, heat, sweat, friction and oral CC contraception exacerbate disease symptoms. Clinical variants of Darier CC disease include hypertrophic, vesicobullous, hypopigmented, cornifying, CC zosteriform or linear, acute and comedonal subtypes. Comedonal Darier CC disease is characterized by the coexistence of acne-like comedonal CC lesions with typical Darier hyperkeratotic papules on light-exposed CC areas. At histopathologic level, comedonal Darier disease differs from CC classic Darier disease in the prominent follicular involvement and the CC presence of greatly elongated dermal villi. CC {ECO:0000269|PubMed:10080178, ECO:0000269|PubMed:10441323, CC ECO:0000269|PubMed:10441324, ECO:0000269|PubMed:10441325, CC ECO:0000269|PubMed:19995371, ECO:0000269|PubMed:28035777}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 1]: Ubiquitous housekeeping isoform. CC -!- MISCELLANEOUS: [Isoform 2]: Cardiac/slow twitch, muscle specific CC isoform. Has a lower affinity for calcium and a higher catalytic CC turnover rate. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: May be due to intron retention. Shows a CC lower apparent affinity for cytosolic calcium than isoform 2 and a CC catalytic turnover rate similar to isoform 1. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IIA subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG57266.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; M23114; AAA53193.1; -; mRNA. DR EMBL; M23116; AAA52757.1; -; Genomic_DNA. DR EMBL; M23115; AAA53194.1; -; mRNA. DR EMBL; M23278; AAA52758.1; -; Genomic_DNA. DR EMBL; M23116; AAA52758.1; JOINED; Genomic_DNA. DR EMBL; AC006088; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035588; AAH35588.1; -; mRNA. DR EMBL; AK293877; BAG57266.1; ALT_INIT; mRNA. DR EMBL; AY186578; AAO47398.1; -; mRNA. DR CCDS; CCDS9143.1; -. [P16615-2] DR CCDS; CCDS9144.1; -. [P16615-1] DR PIR; A31981; A31981. DR PIR; B31981; B31981. DR RefSeq; NP_001672.1; NM_001681.3. [P16615-2] DR RefSeq; NP_733765.1; NM_170665.3. [P16615-1] DR RefSeq; XP_005253945.1; XM_005253888.2. DR RefSeq; XP_011536704.1; XM_011538402.2. [P16615-3] DR PDB; 5ZTF; X-ray; 3.45 A; A=1-1042. DR PDB; 6JJU; X-ray; 3.20 A; A=1-993. DR PDB; 6LLE; EM; 2.90 A; A=1-1042. DR PDB; 6LLY; EM; 2.80 A; A=1-1042. DR PDB; 6LN5; EM; 2.80 A; A=1-1031. DR PDB; 6LN6; EM; 2.90 A; A=1-1031. DR PDB; 6LN7; EM; 2.80 A; A=1-1031. DR PDB; 6LN8; EM; 3.10 A; A=1-1031. DR PDB; 6LN9; EM; 3.40 A; A=1-1031. DR PDB; 7BT2; X-ray; 3.00 A; A=1-993. DR PDB; 7E7S; EM; 3.30 A; A=1-1042. DR PDB; 7W7T; EM; 3.40 A; A=1-1042. DR PDB; 7W7U; EM; 3.00 A; A=1-1042. DR PDB; 7W7V; EM; 3.00 A; A=1-1042. DR PDB; 7W7W; EM; 3.20 A; A=1-1042. DR PDBsum; 5ZTF; -. DR PDBsum; 6JJU; -. DR PDBsum; 6LLE; -. DR PDBsum; 6LLY; -. DR PDBsum; 6LN5; -. DR PDBsum; 6LN6; -. DR PDBsum; 6LN7; -. DR PDBsum; 6LN8; -. DR PDBsum; 6LN9; -. DR PDBsum; 7BT2; -. DR PDBsum; 7E7S; -. DR PDBsum; 7W7T; -. DR PDBsum; 7W7U; -. DR PDBsum; 7W7V; -. DR PDBsum; 7W7W; -. DR AlphaFoldDB; P16615; -. DR BMRB; P16615; -. DR EMDB; EMD-0912; -. DR EMDB; EMD-0915; -. DR EMDB; EMD-0924; -. DR EMDB; EMD-0925; -. DR EMDB; EMD-0926; -. DR EMDB; EMD-0927; -. DR EMDB; EMD-0928; -. DR EMDB; EMD-31003; -. DR EMDB; EMD-32347; -. DR EMDB; EMD-32348; -. DR EMDB; EMD-32349; -. DR EMDB; EMD-32350; -. DR EMDB; EMD-33711; -. DR EMDB; EMD-33712; -. DR EMDB; EMD-33713; -. DR EMDB; EMD-33714; -. DR EMDB; EMD-33717; -. DR SMR; P16615; -. DR BioGRID; 106978; 338. DR CORUM; P16615; -. DR DIP; DIP-33868N; -. DR IntAct; P16615; 158. DR MINT; P16615; -. DR STRING; 9606.ENSP00000440045; -. DR BindingDB; P16615; -. DR ChEMBL; CHEMBL3901; -. DR DrugBank; DB01189; Desflurane. DR DrugBank; DB06157; Istaroxime. DR DrugBank; DB00867; Ritodrine. DR DrugBank; DB01236; Sevoflurane. DR TCDB; 3.A.3.2.7; the p-type atpase (p-atpase) superfamily. DR GlyGen; P16615; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P16615; -. DR MetOSite; P16615; -. DR PhosphoSitePlus; P16615; -. DR SwissPalm; P16615; -. DR BioMuta; ATP2A2; -. DR DMDM; 114312; -. DR EPD; P16615; -. DR jPOST; P16615; -. DR MassIVE; P16615; -. DR MaxQB; P16615; -. DR PaxDb; 9606-ENSP00000440045; -. DR PeptideAtlas; P16615; -. DR ProteomicsDB; 53385; -. [P16615-1] DR ProteomicsDB; 53386; -. [P16615-2] DR ProteomicsDB; 53387; -. [P16615-3] DR ProteomicsDB; 53388; -. [P16615-4] DR ProteomicsDB; 53389; -. [P16615-5] DR Pumba; P16615; -. DR Antibodypedia; 18505; 500 antibodies from 40 providers. DR DNASU; 488; -. DR Ensembl; ENST00000308664.10; ENSP00000311186.6; ENSG00000174437.18. [P16615-2] DR Ensembl; ENST00000539276.7; ENSP00000440045.2; ENSG00000174437.18. [P16615-1] DR GeneID; 488; -. DR KEGG; hsa:488; -. DR MANE-Select; ENST00000539276.7; ENSP00000440045.2; NM_170665.4; NP_733765.1. DR UCSC; uc001tqk.5; human. [P16615-1] DR AGR; HGNC:812; -. DR CTD; 488; -. DR DisGeNET; 488; -. DR GeneCards; ATP2A2; -. DR HGNC; HGNC:812; ATP2A2. DR HPA; ENSG00000174437; Group enriched (heart muscle, skeletal muscle, tongue). DR MalaCards; ATP2A2; -. DR MIM; 101900; phenotype. DR MIM; 108740; gene. DR MIM; 124200; phenotype. DR neXtProt; NX_P16615; -. DR OpenTargets; ENSG00000174437; -. DR Orphanet; 79151; Acrokeratosis verruciformis of Hopf. DR Orphanet; 218; Darier disease. DR PharmGKB; PA71; -. DR VEuPathDB; HostDB:ENSG00000174437; -. DR eggNOG; KOG0202; Eukaryota. DR GeneTree; ENSGT00940000159986; -. DR InParanoid; P16615; -. DR OMA; PLWNNMM; -. DR OrthoDB; 203629at2759; -. DR PhylomeDB; P16615; -. DR TreeFam; TF300651; -. DR PathwayCommons; P16615; -. DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi. DR Reactome; R-HSA-418359; Reduction of cytosolic Ca++ levels. DR Reactome; R-HSA-5578775; Ion homeostasis. DR Reactome; R-HSA-936837; Ion transport by P-type ATPases. DR SignaLink; P16615; -. DR SIGNOR; P16615; -. DR BioGRID-ORCS; 488; 820 hits in 1166 CRISPR screens. DR ChiTaRS; ATP2A2; human. DR GenomeRNAi; 488; -. DR Pharos; P16615; Tchem. DR PRO; PR:P16615; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P16615; Protein. DR Bgee; ENSG00000174437; Expressed in skeletal muscle tissue of biceps brachii and 212 other cell types or tissues. DR ExpressionAtlas; P16615; baseline and differential. DR GO; GO:0090534; C:calcium ion-transporting ATPase complex; IDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0014801; C:longitudinal sarcoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0031095; C:platelet dense tubular network membrane; TAS:Reactome. DR GO; GO:0097470; C:ribbon synapse; IEA:Ensembl. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0005509; F:calcium ion binding; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0106222; F:lncRNA binding; IEA:Ensembl. DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:BHF-UCL. DR GO; GO:0086039; F:P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential; IDA:BHF-UCL. DR GO; GO:0044548; F:S100 protein binding; IPI:UniProtKB. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:ARUK-UCL. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB. DR GO; GO:0016240; P:autophagosome membrane docking; IDA:UniProtKB. DR GO; GO:1990036; P:calcium ion import into sarcoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:1903515; P:calcium ion transport from cytosol to endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IDA:BHF-UCL. DR GO; GO:0008544; P:epidermis development; TAS:ProtInc. DR GO; GO:0006984; P:ER-nucleus signaling pathway; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:BHF-UCL. DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; IDA:UniProtKB. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome. DR GO; GO:0045822; P:negative regulation of heart contraction; IEA:Ensembl. DR GO; GO:1900121; P:negative regulation of receptor binding; IMP:ARUK-UCL. DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl. DR GO; GO:0140056; P:organelle localization by membrane tethering; IDA:UniProtKB. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0032470; P:positive regulation of endoplasmic reticulum calcium ion concentration; IDA:BHF-UCL. DR GO; GO:0010460; P:positive regulation of heart rate; TAS:BHF-UCL. DR GO; GO:1903233; P:regulation of calcium ion-dependent exocytosis of neurotransmitter; IEA:Ensembl. DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome. DR GO; GO:0098909; P:regulation of cardiac muscle cell action potential involved in regulation of contraction; ISS:BHF-UCL. DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; IDA:BHF-UCL. DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IDA:BHF-UCL. DR GO; GO:0002026; P:regulation of the force of heart contraction; IEA:Ensembl. DR GO; GO:0055119; P:relaxation of cardiac muscle; IDA:BHF-UCL. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:ParkinsonsUK-UCL. DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; TAS:BHF-UCL. DR GO; GO:0033292; P:T-tubule organization; IEA:Ensembl. DR GO; GO:0014883; P:transition between fast and slow fiber; IEA:Ensembl. DR CDD; cd02083; P-type_ATPase_SERCA; 1. DR Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1. DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C. DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N. DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N. DR InterPro; IPR018303; ATPase_P-typ_P_site. DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf. DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf. DR InterPro; IPR036412; HAD-like_sf. DR InterPro; IPR023214; HAD_sf. DR InterPro; IPR005782; P-type_ATPase_IIA. DR InterPro; IPR001757; P_typ_ATPase. DR InterPro; IPR044492; P_typ_ATPase_HD_dom. DR NCBIfam; TIGR01116; ATPase-IIA1_Ca; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 2. DR PANTHER; PTHR42861; CALCIUM-TRANSPORTING ATPASE; 1. DR PANTHER; PTHR42861:SF18; SARCOPLASMIC_ENDOPLASMIC RETICULUM CALCIUM ATPASE 2; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF00689; Cation_ATPase_C; 1. DR Pfam; PF00690; Cation_ATPase_N; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR Pfam; PF00702; Hydrolase; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00120; HATPASE. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SMART; SM00831; Cation_ATPase_N; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1. DR PROSITE; PS00154; ATPASE_E1_E2; 1. DR Genevisible; P16615; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Calcium; KW Calcium transport; Disease variant; Disulfide bond; Endoplasmic reticulum; KW Epilepsy; Ion transport; Magnesium; Membrane; Metal-binding; Nitration; KW Nucleotide-binding; Phosphoprotein; Reference proteome; KW Sarcoplasmic reticulum; Translocase; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..1042 FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 2" FT /id="PRO_0000046196" FT TOPO_DOM 1..48 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 49..69 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 70..89 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 90..110 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 111..253 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 254..273 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 274..295 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 296..313 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 314..756 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 757..776 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 777..786 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 787..807 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 808..827 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 828..850 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 851..896 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 897..916 FT /note="Helical; Name=8" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 917..929 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 930..948 FT /note="Helical; Name=9" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 949..963 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 964..984 FT /note="Helical; Name=10" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 985..1042 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 575..594 FT /note="Interaction with HAX1" FT /evidence="ECO:0000269|PubMed:18971376" FT REGION 787..807 FT /note="Interaction with PLN" FT /evidence="ECO:0000250|UniProtKB:P04191" FT REGION 788..1042 FT /note="Interaction with TMEM64 and PDIA3" FT /evidence="ECO:0000250|UniProtKB:O55143" FT REGION 931..942 FT /note="Interaction with PLN" FT /evidence="ECO:0000250|UniProtKB:P04191" FT ACT_SITE 351 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 304 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 305 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 307 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 309 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 351 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 353 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 353 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 442 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 489 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 514 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 559 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 624 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 625 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 626 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 677 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 683 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 702 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 705 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 767 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 770 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 795 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 798 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 799 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 799 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11607" FT BINDING 907 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT MOD_RES 38 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O55143" FT MOD_RES 294 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000269|PubMed:16399855" FT MOD_RES 295 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000269|PubMed:16399855" FT MOD_RES 441 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q64578" FT MOD_RES 531 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O55143" FT MOD_RES 580 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 663 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT DISULFID 875..887 FT /evidence="ECO:0000250|UniProtKB:P11607" FT VAR_SEQ 155..181 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039392" FT VAR_SEQ 994..1042 FT /note="GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS -> FT AILE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:2844796" FT /id="VSP_000358" FT VAR_SEQ 994..1042 FT /note="GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS -> FT VLSSEL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12659872" FT /id="VSP_039393" FT VAR_SEQ 994..1042 FT /note="GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS -> FT DIIK (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_039394" FT VARIANT 23 FT /note="G -> E (in DD; dbSNP:rs28929478)" FT /evidence="ECO:0000269|PubMed:10080178" FT /id="VAR_008608" FT VARIANT 39 FT /note="N -> T (in DD)" FT /evidence="ECO:0000269|PubMed:10441325" FT /id="VAR_008609" FT VARIANT 41 FT /note="Missing (in DD; comedonal type)" FT /evidence="ECO:0000269|PubMed:19995371" FT /id="VAR_063398" FT VARIANT 47 FT /note="K -> KMFLTGK (in DD)" FT /id="VAR_008610" FT VARIANT 65 FT /note="L -> S (in DD; severe form)" FT /id="VAR_008611" FT VARIANT 74..108 FT /note="Missing (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079685" FT VARIANT 101 FT /note="N -> S (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079686" FT VARIANT 131 FT /note="R -> Q (in DD; dbSNP:rs121912738)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_008612" FT VARIANT 160 FT /note="P -> L (in DD)" FT /id="VAR_008613" FT VARIANT 186 FT /note="S -> P (in DD)" FT /id="VAR_008614" FT VARIANT 194..197 FT /note="Missing (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079687" FT VARIANT 211 FT /note="G -> D (in DD; severe form)" FT /id="VAR_008615" FT VARIANT 223 FT /note="V -> M (in DD)" FT /id="VAR_008616" FT VARIANT 268 FT /note="C -> F (in DD; haemorrhagic lesions; FT dbSNP:rs121912733)" FT /id="VAR_008617" FT VARIANT 310 FT /note="G -> V (in DD)" FT /id="VAR_008618" FT VARIANT 318 FT /note="C -> R (in DD; severe form)" FT /id="VAR_008619" FT VARIANT 348 FT /note="I -> T (in DD)" FT /id="VAR_008620" FT VARIANT 357 FT /note="T -> K (in DD)" FT /evidence="ECO:0000269|PubMed:10080178" FT /id="VAR_009508" FT VARIANT 412 FT /note="E -> G (in DD)" FT /id="VAR_008621" FT VARIANT 495 FT /note="S -> F (in DD)" FT /evidence="ECO:0000269|PubMed:10080178" FT /id="VAR_008622" FT VARIANT 560 FT /note="C -> R (in DD; neuropsychiatric phenotype; FT dbSNP:rs121912734)" FT /evidence="ECO:0000269|PubMed:10441325" FT /id="VAR_008623" FT VARIANT 590 FT /note="L -> P (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079688" FT VARIANT 602 FT /note="P -> L (in AKV; no effect on protein abundance; loss FT of calcium ion transmembrane transport; dbSNP:rs121912737)" FT /evidence="ECO:0000269|PubMed:12542527" FT /id="VAR_017532" FT VARIANT 625 FT /note="G -> A (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079689" FT VARIANT 626 FT /note="D -> E (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079690" FT VARIANT 666..1042 FT /note="Missing (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079691" FT VARIANT 672 FT /note="A -> P (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079692" FT VARIANT 675 FT /note="F -> S (in DD; multiple neuropsychiatric features)" FT /id="VAR_008624" FT VARIANT 683 FT /note="K -> E (in DD; depression)" FT /id="VAR_008625" FT VARIANT 691 FT /note="Q -> P (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079693" FT VARIANT 702 FT /note="D -> N (in DD; moderate form)" FT /id="VAR_008626" FT VARIANT 745 FT /note="A -> D (in DD; moderate form)" FT /id="VAR_008627" FT VARIANT 749 FT /note="G -> R (in DD)" FT /evidence="ECO:0000269|PubMed:10080178" FT /id="VAR_009509" FT VARIANT 750 FT /note="R -> W (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079694" FT VARIANT 754 FT /note="Missing (in DD)" FT /id="VAR_008628" FT VARIANT 765 FT /note="S -> L (in DD)" FT /evidence="ECO:0000269|PubMed:10441325" FT /id="VAR_008629" FT VARIANT 765 FT /note="S -> W (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079695" FT VARIANT 767 FT /note="N -> S (in DD; haemorrhagic lesions and FT neuropsychiatric phenotype; dbSNP:rs121912732)" FT /id="VAR_008630" FT VARIANT 769 FT /note="G -> R (in DD; dbSNP:rs121912736)" FT /id="VAR_008631" FT VARIANT 803 FT /note="A -> T (in DD; mild/moderate form)" FT /id="VAR_008632" FT VARIANT 838 FT /note="A -> P (in DD; severe form; petit mal epilepsy)" FT /id="VAR_008633" FT VARIANT 843 FT /note="V -> F (in DD; depression)" FT /id="VAR_008634" FT VARIANT 849 FT /note="G -> GG (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079696" FT VARIANT 875 FT /note="C -> G (in DD; retinitis pigmentosa)" FT /id="VAR_008635" FT VARIANT 900 FT /note="L -> P (in DD)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_079697" FT VARIANT 920 FT /note="S -> Y (in DD; mild/moderate/severe form; one FT patient with epilepsy)" FT /id="VAR_008636" FT VARIANT 943 FT /note="H -> R (in DD; learning difficulties)" FT /evidence="ECO:0000269|PubMed:28035777" FT /id="VAR_008637" FT VARIANT 975 FT /note="P -> R (in DD)" FT /id="VAR_008638" FT MUTAGEN 256 FT /note="F->V: No effect on interaction with VMP1." FT /evidence="ECO:0000269|PubMed:28890335" FT HELIX 4..6 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 9..15 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 20..22 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 26..35 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 49..56 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 60..77 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 78..80 FT /evidence="ECO:0007829|PDB:6LN5" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:7W7W" FT HELIX 86..88 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 89..116 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 118..121 FT /evidence="ECO:0007829|PDB:6LN5" FT STRAND 126..131 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:6LN5" FT STRAND 138..141 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 150..153 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 154..156 FT /evidence="ECO:0007829|PDB:6LLE" FT STRAND 161..171 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 173..176 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 178..181 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 201..203 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:6LN5" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:6LN5" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 227..229 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 231..241 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 248..274 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 275..277 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:7W7V" FT STRAND 281..284 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 288..304 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 311..328 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 331..336 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 337..339 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 341..344 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 347..350 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 352..356 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 362..375 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 377..384 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 388..391 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 395..397 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 404..406 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 408..420 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 425..428 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 429..432 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 433..438 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 440..451 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 460..462 FT /evidence="ECO:0007829|PDB:6LN5" FT HELIX 464..467 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 470..478 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 479..488 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 489..492 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 493..500 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 504..506 FT /evidence="ECO:0007829|PDB:6LN6" FT STRAND 511..515 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 517..523 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 524..529 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 532..535 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 538..553 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 554..556 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 559..568 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 572..574 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 580..586 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 587..599 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 606..615 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 619..623 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 628..637 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 639..641 FT /evidence="ECO:0007829|PDB:6JJU" FT TURN 648..650 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 651..653 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 654..658 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 662..671 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 674..677 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 680..692 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 697..701 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 704..706 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 707..712 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 713..719 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 724..729 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 731..734 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 740..780 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 788..796 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 797..799 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 800..805 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 806..808 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 813..817 FT /evidence="ECO:0007829|PDB:6LN5" FT STRAND 823..825 FT /evidence="ECO:0007829|PDB:6JJU" FT HELIX 830..856 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 859..861 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 867..870 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 872..874 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 875..881 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 882..884 FT /evidence="ECO:0007829|PDB:6LN5" FT HELIX 888..891 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 894..912 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 915..919 FT /evidence="ECO:0007829|PDB:6LLY" FT TURN 921..923 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 926..928 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 930..948 FT /evidence="ECO:0007829|PDB:6LLY" FT STRAND 949..951 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 952..955 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 963..973 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 975..989 FT /evidence="ECO:0007829|PDB:6LLY" FT HELIX 1016..1030 FT /evidence="ECO:0007829|PDB:6LLY" SQ SEQUENCE 1042 AA; 114757 MW; 5462FF2DA7FB630A CRC64; MENAHTKTVE EVLGHFGVNE STGLSLEQVK KLKERWGSNE LPAEEGKTLL ELVIEQFEDL LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILVA NAIVGVWQER NAENAIEALK EYEPEMGKVY RQDRKSVQRI KAKDIVPGDI VEIAVGDKVP ADIRLTSIKS TTLRVDQSIL TGESVSVIKH TDPVPDPRAV NQDKKNMLFS GTNIAAGKAM GVVVATGVNT EIGKIRDEMV ATEQERTPLQ QKLDEFGEQL SKVISLICIA VWIINIGHFN DPVHGGSWIR GAIYYFKIAV ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ MSVCRMFILD RVEGDTCSLN EFTITGSTYA PIGEVHKDDK PVNCHQYDGL VELATICALC NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTELK GLSKIERANA CNSVIKQLMK KEFTLEFSRD RKSMSVYCTP NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTSGV KQKIMSVIRE WGSGSDTLRC LALATHDNPL RREEMHLEDS ANFIKYETNL TFVGCVGMLD PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK AFTGREFDEL NPSAQRDACL NARCFARVEP SHKSKIVEFL QSFDEITAMT GDGVNDAPAL KKAEIGIAMG SGTAVAKTAS EMVLADDNFS TIVAAVEEGR AIYNNMKQFI RYLISSNVGE VVCIFLTAAL GFPEALIPVQ LLWVNLVTDG LPATALGFNP PDLDIMNKPP RNPKEPLISG WLFFRYLAIG CYVGAATVGA AAWWFIAADG GPRVSFYQLS HFLQCKEDNP DFEGVDCAIF ESPYPMTMAL SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE PLPLIFQITP LNVTQWLMVL KISLPVILMD ETLKFVARNY LEPGKECVQP ATKSCSFSAC TDGISWPFVL LIMPLVIWVY STDTNFSDMF WS //