ID AT2A2_RAT Reviewed; 1043 AA. AC P11507; P11508; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 2; DE Short=SERCA2; DE Short=SR Ca(2+)-ATPase 2; DE EC=7.2.2.10; 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; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=2844797; DOI=10.1016/s0021-9258(18)68142-6; RA Gunteski-Hamblin A.-M., Greeb J., Shull G.E.; RT "A novel Ca2+ pump expressed in brain, kidney, and stomach is encoded by an RT alternative transcript of the slow-twitch muscle sarcoplasmic reticulum Ca- RT ATPase gene. Identification of cDNAs encoding Ca2+ and other cation- RT transporting ATPases using an oligonucleotide probe derived from the ATP- RT binding site."; RL J. Biol. Chem. 263:15032-15040(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Heart; RX PubMed=2542094; DOI=10.1016/0014-5793(89)80010-9; RA Lompre A.M., de la Bastie D., Boheler K.R., Schwartz K.; RT "Characterization and expression of the rat heart sarcoplasmic reticulum RT Ca2+-ATPase mRNA."; RL FEBS Lett. 249:35-41(1989). RN [3] RP NITRATION AT TYR-294 AND TYR-295. RX PubMed=10359649; DOI=10.1042/bj3400657; RA Viner R.I., Ferrington D.A., Williams T.D., Bigelow D.J., Schoeneich C.; RT "Protein modification during biological aging: selective tyrosine nitration RT of the SERCA2a isoform of the sarcoplasmic reticulum Ca2+-ATPase in RT skeletal muscle."; RL Biochem. J. 340:657-669(1999). RN [4] 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 [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38; SER-661 AND SER-663, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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). In coordination with FLVCR2 mediates heme-stimulated CC switching from mitochondrial ATP synthesis to thermogenesis (By CC similarity). {ECO:0000250|UniProtKB:O55143, CC ECO:0000250|UniProtKB:P16615}. 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:0000250|UniProtKB:P16615}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; CC Evidence={ECO:0000250|UniProtKB:P16615}; 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:O55143, CC ECO:0000250|UniProtKB:P04191, ECO:0000250|UniProtKB:P16615, CC ECO:0000250|UniProtKB:Q8R429}. CC -!- SUBUNIT: Interacts with sarcolipin (SLN); the interaction inhibits CC ATP2A2 Ca(2+) affinity. Interacts with phospholamban (PLN); the CC interaction inhibits ATP2A2 Ca(2+) affinity (By similarity). Interacts CC with myoregulin (MRLN) (By similarity). Interacts with DWORF (By CC similarity). Interacts with HAX1 (By similarity). Interacts with S100A8 CC and S100A9 (By similarity). Interacts with SLC35G1 and STIM1. Interacts CC with TMEM203 (By similarity). Interacts with TMEM64 and PDIA3 (By CC similarity). Interacts with TMX1 (By similarity). Interacts with TMX2 CC (By similarity). Interacts with VMP1; VMP1 competes with PLN and SLN to CC prevent them from forming an inhibitory complex with ATP2A2. Interacts CC with ULK1 (By similarity). Interacts with S100A1 in a Ca(2+)-dependent CC manner (By similarity). Interacts with TUNAR (By similarity). Interacts CC with FLVCR2; this interaction occurs in the absence of heme and CC promotes ATP2A2 proteasomal degradation; this complex is dissociated CC upon heme binding. Interacts with FNIP1. {ECO:0000250|UniProtKB:O55143, CC ECO:0000250|UniProtKB:P04191, ECO:0000250|UniProtKB:P16615, CC ECO:0000250|UniProtKB:Q8R429}. CC -!- SUBUNIT: [Isoform 1]: Interacts with TRAM2 (via C-terminus). CC {ECO:0000250|UniProtKB:P16615}. CC -!- INTERACTION: CC P11507; Q9EQU3: Tlr9; Xeno; NbExp=4; IntAct=EBI-916319, EBI-9979528; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:O55143}; Multi-pass membrane protein CC {ECO:0000255}. Sarcoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:O55143}; 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=2; CC Name=1; Synonyms=Atp2a2b, SERCA2b; CC IsoId=P11507-1; Sequence=Displayed; CC Name=2; Synonyms=Atp2a2a, SERCA2a; CC IsoId=P11507-2; Sequence=VSP_000362; CC -!- TISSUE SPECIFICITY: Isoform 2 is highly expressed in heart and slow CC twitch skeletal muscle. Isoform 1 is widely expressed. 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:0000250|UniProtKB:O55143}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IIA subfamily. {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; J04022; AAA40785.1; -; mRNA. DR EMBL; J04024; AAA40787.1; -; mRNA. DR EMBL; J04023; AAA40786.1; -; mRNA. DR EMBL; X15635; CAA33645.1; -; mRNA. DR PIR; A31982; A31982. DR PIR; B31982; B31982. DR RefSeq; NP_001103609.1; NM_001110139.2. [P11507-2] DR RefSeq; NP_001104293.1; NM_001110823.2. [P11507-1] DR AlphaFoldDB; P11507; -. DR SMR; P11507; -. DR BioGRID; 248313; 6. DR CORUM; P11507; -. DR IntAct; P11507; 9. DR MINT; P11507; -. DR STRING; 10116.ENSRNOP00000024347; -. DR BindingDB; P11507; -. DR ChEMBL; CHEMBL3585237; -. DR DrugCentral; P11507; -. DR CarbonylDB; P11507; -. DR GlyGen; P11507; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11507; -. DR PhosphoSitePlus; P11507; -. DR jPOST; P11507; -. DR PaxDb; 10116-ENSRNOP00000024347; -. DR PeptideAtlas; P11507; -. DR Ensembl; ENSRNOT00000001738.8; ENSRNOP00000001738.7; ENSRNOG00000001285.9. [P11507-1] DR Ensembl; ENSRNOT00055026015; ENSRNOP00055021197; ENSRNOG00055015092. [P11507-1] DR Ensembl; ENSRNOT00060003502; ENSRNOP00060002394; ENSRNOG00060002173. [P11507-1] DR Ensembl; ENSRNOT00065010948; ENSRNOP00065008043; ENSRNOG00065006868. [P11507-1] DR GeneID; 29693; -. DR KEGG; rno:29693; -. DR UCSC; RGD:2174; rat. [P11507-1] DR AGR; RGD:2174; -. DR CTD; 488; -. DR RGD; 2174; Atp2a2. DR eggNOG; KOG0202; Eukaryota. DR GeneTree; ENSGT00940000159986; -. DR InParanoid; P11507; -. DR OrthoDB; 203629at2759; -. DR PhylomeDB; P11507; -. DR Reactome; R-RNO-418359; Reduction of cytosolic Ca++ levels. DR Reactome; R-RNO-5578775; Ion homeostasis. DR Reactome; R-RNO-936837; Ion transport by P-type ATPases. DR PRO; PR:P11507; -. DR Proteomes; UP000002494; Chromosome 12. DR Bgee; ENSRNOG00000001285; Expressed in heart and 19 other cell types or tissues. DR GO; GO:0061831; C:apical ectoplasmic specialization; IDA:RGD. DR GO; GO:0090534; C:calcium ion-transporting ATPase complex; ISO:RGD. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:RGD. DR GO; GO:0014801; C:longitudinal sarcoplasmic reticulum; ISO:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0120025; C:plasma membrane bounded cell projection; IDA:RGD. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0097470; C:ribbon synapse; ISO:RGD. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:RGD. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IDA:RGD. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0005509; F:calcium ion binding; IDA:RGD. DR GO; GO:0019899; F:enzyme binding; ISO:RGD. DR GO; GO:0106222; F:lncRNA binding; ISO:RGD. DR GO; GO:0031775; F:lutropin-choriogonadotropic hormone receptor binding; IPI:RGD. DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:RGD. 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; ISO:RGD. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD. 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; IDA:BHF-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:0006816; P:calcium ion transport; IDA:RGD. DR GO; GO:1903515; P:calcium ion transport from cytosol to endoplasmic reticulum; ISO:RGD. DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; ISO:RGD. DR GO; GO:0034605; P:cellular response to heat; IEP:RGD. DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:RGD. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISO:RGD. DR GO; GO:0006984; P:ER-nucleus signaling pathway; ISO:RGD. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:RGD. DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; ISS:UniProtKB. DR GO; GO:0045822; P:negative regulation of heart contraction; ISO:RGD. DR GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD. DR GO; GO:0140056; P:organelle localization by membrane tethering; ISS:UniProtKB. DR GO; GO:0006996; P:organelle organization; ISO:RGD. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:RGD. DR GO; GO:0032470; P:positive regulation of endoplasmic reticulum calcium ion concentration; ISO:RGD. DR GO; GO:1903233; P:regulation of calcium ion-dependent exocytosis of neurotransmitter; ISO:RGD. DR GO; GO:0098909; P:regulation of cardiac muscle cell action potential involved in regulation of contraction; IDA: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; ISO:RGD. DR GO; GO:0055119; P:relaxation of cardiac muscle; IDA:BHF-UCL. DR GO; GO:0090076; P:relaxation of skeletal muscle; IEP:RGD. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEP:ParkinsonsUK-UCL. DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD. DR GO; GO:0043434; P:response to peptide hormone; IDA:UniProtKB. DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; IDA:RGD. DR GO; GO:0033292; P:T-tubule organization; ISO:RGD. DR GO; GO:0014883; P:transition between fast and slow fiber; ISO:RGD. 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; P11507; RN. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Calcium; Calcium transport; KW Disulfide bond; Endoplasmic reticulum; Ion transport; Magnesium; Membrane; KW Metal-binding; Nitration; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Sarcoplasmic reticulum; Translocase; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..1043 FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 2" FT /id="PRO_0000046200" 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..1043 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..1043 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:0007744|PubMed:22673903" FT MOD_RES 294 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000269|PubMed:10359649, FT ECO:0000269|PubMed:16399855" FT MOD_RES 295 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000269|PubMed:10359649, FT 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:0000250|UniProtKB:P16615" FT MOD_RES 661 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 663 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT DISULFID 875..887 FT /evidence="ECO:0000250|UniProtKB:P11607" FT VAR_SEQ 994..1043 FT /note="GKECAQPATKPSCSLSACTDGISWPFVLLIMPLVVWVYSTDTNFSDMFWS FT -> AILE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:2542094, FT ECO:0000303|PubMed:2844797" FT /id="VSP_000362" SQ SEQUENCE 1043 AA; 114768 MW; 4B0B476BFD97F390 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 EFTITGSTYA PIGEVQKDDK PVKCHQYDGL VELATICALC NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTELK GLSKIERANA CNSVIKQLMK KEFTLEFSRD RKSMSVYCTP NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTPGV KQKIMSVIRE WGSGSDTLRC LALATHDNPL RREEMHLEDS 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 DFEGVDCAIF ESPYPMTMAL SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE PLPLIFQITP LNLTQWLMVL KISLPVILMD ETLKFVARNY LEPGKECAQP ATKPSCSLSA CTDGISWPFV LLIMPLVVWV YSTDTNFSDM FWS //