AT2A2_MOUSE
ID AT2A2_MOUSE Reviewed; 1044 AA.
AC O55143; Q9R2A9; Q9WUT5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 214.
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|MGI:MGI:88110};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=129/SvJ, and NIH Swiss; TISSUE=Embryo;
RX PubMed=10656932; DOI=10.1007/s003350010030;
RA Ver Heyen M., Reed T.D., Blough R.E., Zilberman A.L., Loukianov E.,
RA Van Baelen K., Raeymaekers L., Periasamy M., Wutack F.;
RT "Structure and organization of the mouse Atp2a2 gene encoding the
RT sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) isoforms.";
RL Mamm. Genome 11:159-163(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP PROTEIN SEQUENCE OF 604-611 AND 638-655, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP INTERACTION WITH S100A8 AND S100A9.
RX PubMed=18403730; DOI=10.1161/circresaha.107.167544;
RA Boyd J.H., Kan B., Roberts H., Wang Y., Walley K.R.;
RT "S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via
RT the receptor for advanced glycation end products.";
RL Circ. Res. 102:1239-1246(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38; SER-531 AND SER-663, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=22355118; DOI=10.1073/pnas.1120172109;
RA Swift F., Franzini-Armstrong C., Oeyehaug L., Enger U.H., Andersson K.B.,
RA Christensen G., Sejersted O.M., Louch W.E.;
RT "Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule
RT remodeling after Serca2 knockout.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:3997-4001(2012).
RN [10]
RP FUNCTION, INTERACTION WITH PLN, AND ACTIVITY REGULATION.
RX PubMed=22971924; DOI=10.1007/s10974-012-9319-4;
RA Ha K.N., Gustavsson M., Veglia G.;
RT "Tuning the structural coupling between the transmembrane and cytoplasmic
RT domains of phospholamban to control sarcoplasmic reticulum Ca(2+)-ATPase
RT (SERCA) function.";
RL J. Muscle Res. Cell Motil. 33:485-492(2012).
RN [11]
RP FUNCTION, INTERACTION WITH TMEM64 AND PDIA3, SUBCELLULAR LOCATION, AND
RP INDUCTION.
RX PubMed=23395171; DOI=10.1016/j.cmet.2013.01.002;
RA Kim H., Kim T., Jeong B.C., Cho I.T., Han D., Takegahara N.,
RA Negishi-Koga T., Takayanagi H., Lee J.H., Sul J.Y., Prasad V., Lee S.H.,
RA Choi Y.;
RT "Tmem64 modulates calcium signaling during RANKL-mediated osteoclast
RT differentiation.";
RL Cell Metab. 17:249-260(2013).
RN [12]
RP CATALYTIC ACTIVITY.
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 [13]
RP SEROTONYLATION.
RX PubMed=32116663; DOI=10.3389/fphar.2019.01611;
RA Liu B., Wang D., Luo E., Hou J., Qiao Y., Yan G., Wang Q., Tang C.;
RT "Role of TG2-mediated SERCA2 serotonylation on hypoxic pulmonary vein
RT remodeling.";
RL Front. Pharmacol. 10:1611-1611(2019).
RN [14]
RP INTERACTION WITH TUNAR.
RX PubMed=35036403; DOI=10.3389/fcell.2021.747667;
RA Senis E., Esgleas M., Najas S., Jimenez-Sabado V., Bertani C.,
RA Gimenez-Alejandre M., Escriche A., Ruiz-Orera J., Hergueta-Redondo M.,
RA Jimenez M., Giralt A., Nuciforo P., Alba M.M., Peinado H., Del Toro D.,
RA Hove-Madsen L., Goetz M., Abad M.;
RT "TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation
RT and Neurite Formation by Modulating Calcium Dynamics.";
RL Front. Cell Dev. Biol. 9:747667-747667(2021).
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. Involved in autophagy in response to
CC starvation. Upon interaction with VMP1 and activation, controls ER-
CC isolation membrane contacts for autophagosome formation. Also modulates
CC ER contacts with lipid droplets, mitochondria and endosomes (By
CC similarity). {ECO:0000250|UniProtKB:P16615,
CC ECO:0000269|PubMed:22355118, ECO:0000269|PubMed:22971924}.
CC -!- FUNCTION: [Isoform 2]: Involved in the regulation of the
CC contraction/relaxation cycle (PubMed:23395171). Acts as a regulator of
CC TNFSF11-mediated Ca(2+) signaling pathways via its interaction with
CC TMEM64 which is critical for the TNFSF11-induced CREB1 activation and
CC mitochondrial ROS generation necessary for proper osteoclast generation
CC (PubMed:23395171). Association between TMEM64 and SERCA2 in the ER
CC leads to cytosolic Ca(2+) spiking for activation of NFATC1 and
CC production of mitochondrial ROS, thereby triggering Ca(2+) signaling
CC cascades that promote osteoclast differentiation and activation
CC (PubMed:23395171). {ECO:0000269|PubMed:23395171}.
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 (PubMed:22971924). Inhibited by sarcolipin (SLN) and
CC myoregulin (MRLN). The inhibition is blocked by VMP1 (By similarity).
CC Enhanced by DWORF; DWORF increases activity by displacing sarcolipin
CC (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).
CC Stabilizes SERCA2 in its E2 state (By similarity).
CC {ECO:0000250|UniProtKB:P04191, ECO:0000250|UniProtKB:P16615,
CC ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:22971924}.
CC -!- SUBUNIT: Interacts with sarcolipin (SLN); the interaction inhibits
CC ATP2A2 Ca(2+) affinity (By similarity). Interacts with phospholamban
CC (PLN); the interaction inhibits ATP2A2 Ca(2+) affinity
CC (PubMed:22971924). Interacts with myoregulin (MRLN) (By similarity).
CC Interacts with DWORF (By similarity). Interacts with HAX1. Interacts
CC with S100A8 and S100A9 (PubMed:18403730). Interacts with SLC35G1 and
CC STIM1. Interacts with TMEM203 (By similarity). Interacts with TMEM64
CC and PDIA3 (PubMed:23395171). Interacts with TMX2. Interacts with VMP1;
CC VMP1 competes with PLN and SLN to prevent them from forming an
CC inhibitory complex with ATP2A2. Interacts with ULK1 (By similarity).
CC Interacts with S100A1 in a Ca(2+)-dependent manner (By similarity).
CC Interacts with TUNAR (PubMed:35036403). {ECO:0000250|UniProtKB:P04191,
CC ECO:0000250|UniProtKB:P16615, ECO:0000250|UniProtKB:Q8R429,
CC ECO:0000269|PubMed:14749390, ECO:0000269|PubMed:18403730,
CC ECO:0000269|PubMed:22971924, ECO:0000269|PubMed:23395171,
CC ECO:0000269|PubMed:35036403}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with TRAM2 (via C-terminus).
CC {ECO:0000269|PubMed:14749390}.
CC -!- INTERACTION:
CC O55143; Q5S006: Lrrk2; NbExp=9; IntAct=EBI-770763, EBI-2693710;
CC O55143; E2JF22: Piezo1; NbExp=3; IntAct=EBI-770763, EBI-9837938;
CC O55143; Q5S007: LRRK2; Xeno; NbExp=13; IntAct=EBI-770763, EBI-5323863;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23395171}; Multi-pass membrane protein
CC {ECO:0000255}. Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22355118}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Atp2a2b, SERCA2b;
CC IsoId=O55143-1; Sequence=Displayed;
CC Name=2; Synonyms=Atp2a2a, SERCA2a;
CC IsoId=O55143-2; Sequence=VSP_000359;
CC -!- TISSUE SPECIFICITY: Isoform 2 is highly expressed in heart and slow
CC twitch skeletal muscle. Isoform 2 is widely expressed.
CC -!- INDUCTION: Highly up-regulated during osteoclast differentiation.
CC {ECO:0000269|PubMed:23395171}.
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:0000250|UniProtKB:P16615}.
CC -!- PTM: Serotonylated on Gln residues by TGM2 in response to hypoxia,
CC leading to its inactivation. {ECO:0000269|PubMed:32116663}.
CC -!- DISRUPTION PHENOTYPE: Sarcoplasmic reticulum collapse and volume
CC reduction. Although dimensions of cardiomyocyte are not affected, total
CC surface area is significantly increased, resulting in increased T-
CC tubule density. {ECO:0000269|PubMed:22355118}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIA subfamily. {ECO:0000305}.
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DR EMBL; AJ131821; CAB72436.1; -; mRNA.
DR EMBL; AJ223584; CAA11450.1; -; mRNA.
DR EMBL; AF029982; AAD01889.1; -; Genomic_DNA.
DR EMBL; AJ131870; CAB41017.1; -; Genomic_DNA.
DR EMBL; AJ131870; CAB41018.1; -; Genomic_DNA.
DR EMBL; BC054531; AAH54531.1; -; mRNA.
DR EMBL; BC054748; AAH54748.1; -; mRNA.
DR CCDS; CCDS57378.1; -. [O55143-1]
DR CCDS; CCDS57379.1; -. [O55143-2]
DR RefSeq; NP_001103610.1; NM_001110140.3. [O55143-1]
DR RefSeq; NP_033852.1; NM_009722.3. [O55143-2]
DR AlphaFoldDB; O55143; -.
DR SMR; O55143; -.
DR BioGRID; 198249; 54.
DR IntAct; O55143; 50.
DR MINT; O55143; -.
DR STRING; 10090.ENSMUSP00000031423; -.
DR BindingDB; O55143; -.
DR ChEMBL; CHEMBL4523144; -.
DR iPTMnet; O55143; -.
DR PhosphoSitePlus; O55143; -.
DR SwissPalm; O55143; -.
DR EPD; O55143; -.
DR jPOST; O55143; -.
DR MaxQB; O55143; -.
DR PaxDb; O55143; -.
DR PeptideAtlas; O55143; -.
DR PRIDE; O55143; -.
DR ProteomicsDB; 265123; -. [O55143-1]
DR ProteomicsDB; 265124; -. [O55143-2]
DR Antibodypedia; 18505; 435 antibodies from 40 providers.
DR DNASU; 11938; -.
DR Ensembl; ENSMUST00000031423; ENSMUSP00000031423; ENSMUSG00000029467. [O55143-1]
DR Ensembl; ENSMUST00000177974; ENSMUSP00000136104; ENSMUSG00000029467. [O55143-2]
DR Ensembl; ENSMUST00000179939; ENSMUSP00000135935; ENSMUSG00000029467. [O55143-1]
DR GeneID; 11938; -.
DR KEGG; mmu:11938; -.
DR UCSC; uc008zli.2; mouse. [O55143-2]
DR CTD; 488; -.
DR MGI; MGI:88110; Atp2a2.
DR VEuPathDB; HostDB:ENSMUSG00000029467; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000159986; -.
DR HOGENOM; CLU_002360_3_2_1; -.
DR InParanoid; O55143; -.
DR OMA; PLWNNMM; -.
DR PhylomeDB; O55143; -.
DR TreeFam; TF300651; -.
DR BRENDA; 7.2.2.10; 3474.
DR Reactome; R-MMU-418359; Reduction of cytosolic Ca++ levels.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 11938; 25 hits in 72 CRISPR screens.
DR ChiTaRS; Atp2a2; mouse.
DR PRO; PR:O55143; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O55143; protein.
DR Bgee; ENSMUSG00000029467; Expressed in myocardium of ventricle and 262 other tissues.
DR Genevisible; O55143; MM.
DR GO; GO:0061831; C:apical ectoplasmic specialization; ISO:MGI.
DR GO; GO:0090534; C:calcium ion-transporting ATPase complex; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0014704; C:intercalated disc; ISO:MGI.
DR GO; GO:0014801; C:longitudinal sarcoplasmic reticulum; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0120025; C:plasma membrane bounded cell projection; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0097470; C:ribbon synapse; IDA:MGI.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:MGI.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0012506; C:vesicle membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0031775; F:lutropin-choriogonadotropic hormone receptor binding; ISO:MGI.
DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:MGI.
DR GO; GO:0086039; F:P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential; ISS: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; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0016240; P:autophagosome membrane docking; ISS:UniProtKB.
DR GO; GO:1990036; P:calcium ion import into sarcoplasmic reticulum; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; ISO:MGI.
DR GO; GO:1903515; P:calcium ion transport from cytosol to endoplasmic reticulum; ISO:MGI.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IDA:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:MGI.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; IGI:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISO:MGI.
DR GO; GO:0006984; P:ER-nucleus signaling pathway; IMP:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; ISS:UniProtKB.
DR GO; GO:0045822; P:negative regulation of heart contraction; IGI:MGI.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISO:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:MGI.
DR GO; GO:0140056; P:organelle localization by membrane tethering; ISS:UniProtKB.
DR GO; GO:0006996; P:organelle organization; IMP:MGI.
DR GO; GO:0032470; P:positive regulation of endoplasmic reticulum calcium ion concentration; IMP:MGI.
DR GO; GO:1903233; P:regulation of calcium ion-dependent exocytosis of neurotransmitter; IMP:MGI.
DR GO; GO:0098909; P:regulation of cardiac muscle cell action potential involved in regulation of contraction; ISO:MGI.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; ISO:MGI.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:MGI.
DR GO; GO:0006937; P:regulation of muscle contraction; TAS:MGI.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IGI:MGI.
DR GO; GO:0055119; P:relaxation of cardiac muscle; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; ISO:MGI.
DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; IMP:MGI.
DR GO; GO:0003009; P:skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:0033292; P:T-tubule organization; IMP:MGI.
DR GO; GO:0014883; P:transition between fast and slow fiber; IDA:MGI.
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 Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW 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..1044
FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 2"
FT /id="PRO_0000046197"
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..1044
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 575..594
FT /note="Interaction with HAX1"
FT /evidence="ECO:0000250"
FT REGION 787..807
FT /note="Interaction with PLN"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT REGION 788..1044
FT /note="Interaction with TMEM64 and PDIA3"
FT /evidence="ECO:0000269|PubMed:23395171"
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:0007744|PubMed:21183079"
FT MOD_RES 294
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16615"
FT MOD_RES 295
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16615"
FT MOD_RES 441
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64578"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16615"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11507"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT DISULFID 875..887
FT /evidence="ECO:0000250|UniProtKB:P11607"
FT VAR_SEQ 995..1044
FT /note="GKECVQPATKSSCSLSACTDGISWPFVLLIMPLVVWVYSTDTNFSDMFWS
FT -> AILE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10656932"
FT /id="VSP_000359"
SQ SEQUENCE 1044 AA; 114858 MW; 06A753982116C421 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 KVEGDTCSLN EFSITGSTYA PIGEVQKDDK PVKCHQYDGL VELATICALC
NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTELK GLSKIERANA CNSVIKQLMK
KEFTLEFSRD RKSMSVYCTP NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTPGV
KQKIMSVIRE WGSGSDTLRC LALATHDNPL KREEMHLEDS ANFIKYETNL TFVGCVGMLD
PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK AFTGREFDEL
SPSAQRDACL NARCFARVEP SHKSKIVEFL QSFDEITAMT GDGVNDAPAL KKSEIGIAMG
SGTAVAKTAS EMVLADDNFS TIVAAVEEGR AIYNNMKQFI RYLISSNVGE VVCIFLTAAL
GFPEALIPVQ LLWVNLVTDG LPATALGFNP PDLDIMNKPP RNPKEPLISG WLFFRYLAIG
CYVGAATVGA AAWWFIAADG GPRVSFYQLS HFLQCKEDNP DFDGVDCAIF ESPYPMTMAL
SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE PLPLIFQITP
LNLTQWLMVL KISLPVILMD ETLKFVARNY LEQPGKECVQ PATKSSCSLS ACTDGISWPF
VLLIMPLVVW VYSTDTNFSD MFWS
