AT2A2_HUMAN
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 03-AUG-2022, entry version 244.
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 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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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).
CC {ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920,
CC 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 -!- 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 TMX2. Interacts with VMP1; VMP1 competes
CC with PLN and SLN to prevent them from forming an inhibitory complex
CC with ATP2A2 (PubMed:28890335). Interacts with ULK1 (PubMed:28890335).
CC Interacts with S100A1 in a Ca(2+)-dependent manner (PubMed:12804600).
CC Interacts with TUNAR (By similarity). {ECO:0000250|UniProtKB:O55143,
CC ECO:0000250|UniProtKB:P04191, ECO:0000250|UniProtKB:Q8R429,
CC ECO:0000269|PubMed:12804600, ECO:0000269|PubMed:14749390,
CC ECO:0000269|PubMed:18971376, ECO:0000269|PubMed:22084111,
CC ECO:0000269|PubMed:25996873, 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}.
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. [P16615-3]
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 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 AlphaFoldDB; P16615; -.
DR BMRB; P16615; -.
DR SMR; P16615; -.
DR BioGRID; 106978; 286.
DR CORUM; P16615; -.
DR DIP; DIP-33868N; -.
DR IntAct; P16615; 148.
DR MINT; P16615; -.
DR STRING; 9606.ENSP00000440045; -.
DR BindingDB; P16615; -.
DR ChEMBL; CHEMBL3901; -.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB06157; Istaroxime.
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; P16615; -.
DR PeptideAtlas; P16615; -.
DR PRIDE; 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 Antibodypedia; 18505; 435 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 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; 646662at2759; -.
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; 779 hits in 1080 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 210 other tissues.
DR ExpressionAtlas; P16615; baseline and differential.
DR Genevisible; P16615; HS.
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:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0014801; C:longitudinal sarcoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:MGI.
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; TAS: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: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:UniProtKB.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
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; ISS: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:0006874; P:cellular calcium ion homeostasis; IDA:BHF-UCL.
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:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; IDA:UniProtKB.
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: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; ISS: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 Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 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 Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR PRINTS; PR00120; HATPASE.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01116; ATPase-IIA1_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
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 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 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 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
