ID AT2A3_RAT Reviewed; 999 AA. AC P18596; Q8R5I9; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 02-DEC-2020, sequence version 3. DT 27-MAR-2024, entry version 187. DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 3; DE Short=SERCA3; DE Short=SR Ca(2+)-ATPase 3; DE EC=7.2.2.10; DE AltName: Full=Calcium pump 3; GN Name=Atp2a3; 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] (ISOFORM SERCA3A), CHARACTERIZATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Kidney; RX PubMed=2553713; DOI=10.1016/s0021-9258(18)51504-0; RA Burk S.E., Lytton J., McLennan D.H., Shull G.E.; RT "cDNA cloning, functional expression, and mRNA tissue distribution of a RT third organellar Ca2+ pump."; RL J. Biol. Chem. 264:18561-18568(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 869-999 (ISOFORM SERCA3BC), FUNCTION, TISSUE RP SPECIFICITY, AND INDUCTION. RC STRAIN=Wistar Kyoto; RX PubMed=10642281; DOI=10.1161/01.hyp.35.1.91; RA Martin V., Bredoux R., Corvazier E., Papp B., Enouf J.; RT "Platelet Ca(2+)ATPases: a plural, species-specific, and multiple RT hypertension-regulated expression system."; RL Hypertension 35:91-102(2000). CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of CC ATP coupled with the transport of the calcium. Transports calcium ions CC from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. CC Contributes to calcium sequestration involved in muscular CC excitation/contraction. {ECO:0000269|PubMed:10642281}. CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of CC ATP coupled with the transport of calcium. Transports calcium ions from CC the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. CC Contributes to calcium sequestration involved in muscular CC excitation/contraction. {ECO:0000250|UniProtKB:Q93084}. 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:Q93084}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; CC Evidence={ECO:0000250|UniProtKB:Q93084}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P04191}; CC -!- ACTIVITY REGULATION: Inhibited by sarcolipin (SLN), phospholamban (PLN) CC and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF CC increases activity by displacing sarcolipin (SLN), phospholamban (PLN) CC and myoregulin (MRLN) (By similarity). {ECO:0000250|UniProtKB:P04191, CC ECO:0000250|UniProtKB:Q8R429}. CC -!- SUBUNIT: Interacts with sarcolipin (SLN) (By similarity). Interacts CC with phospholamban (PLN) (By similarity). Interacts with myoregulin CC (MRLN). Interacts with DWORF (By similarity). Interacts with VMP1 (By CC similarity). Interacts with TUNAR; the interaction occurs at low levels CC in low glucose conditions and is increased by high glucose levels (By CC similarity). {ECO:0000250|UniProtKB:P04191, CC ECO:0000250|UniProtKB:Q8R429, ECO:0000250|UniProtKB:Q93084}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q93084}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q93084}. Sarcoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q93084}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q93084}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=SERCA3A; CC IsoId=P18596-2; Sequence=Displayed; CC Name=SERCA3BC; CC IsoId=P18596-1; Sequence=VSP_060852; CC -!- TISSUE SPECIFICITY: Found in most tissues. Most abundant in large and CC small intestine, spleen and lung. Also detected in PC12 cells. CC {ECO:0000269|PubMed:10642281, ECO:0000269|PubMed:2553713}. CC -!- INDUCTION: [Isoform SERCA3BC]: Down-regulated in all tissues except CC pancreas in a rat hypertension model. {ECO:0000269|PubMed:10642281}. 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; M30581; AAA42131.1; -; mRNA. DR EMBL; AF458230; AAL78969.1; -; mRNA. DR PIR; A34307; A34307. DR RefSeq; NP_037046.1; NM_012914.1. [P18596-2] DR AlphaFoldDB; P18596; -. DR SMR; P18596; -. DR BioGRID; 247429; 3. DR IntAct; P18596; 1. DR STRING; 10116.ENSRNOP00000060212; -. DR iPTMnet; P18596; -. DR PhosphoSitePlus; P18596; -. DR jPOST; P18596; -. DR PaxDb; 10116-ENSRNOP00000060212; -. DR GeneID; 25391; -. DR KEGG; rno:25391; -. DR AGR; RGD:2175; -. DR CTD; 489; -. DR RGD; 2175; Atp2a3. DR eggNOG; KOG0202; Eukaryota. DR InParanoid; P18596; -. DR OrthoDB; 203629at2759; -. 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:P18596; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD. DR GO; GO:0031090; C:organelle membrane; ISO:RGD. DR GO; GO:0016529; C:sarcoplasmic reticulum; ISO:RGD. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell. 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; ISO:RGD. DR GO; GO:0015085; F:calcium ion transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0030899; F:calcium-dependent ATPase activity; IDA:ARUK-UCL. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; ISO:RGD. DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:ARUK-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:ARUK-UCL. DR GO; GO:1903515; P:calcium ion transport from cytosol to endoplasmic reticulum; ISO:RGD. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IDA:RGD. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:RGD. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:RGD. DR GO; GO:0097421; P:liver regeneration; IEP: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:SF6; SARCOPLASMIC_ENDOPLASMIC RETICULUM CALCIUM ATPASE 3; 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 SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 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. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Calcium; Calcium transport; KW Endoplasmic reticulum; Ion transport; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Reference proteome; KW Sarcoplasmic reticulum; Translocase; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..999 FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 3" FT /id="PRO_0000046205" FT TOPO_DOM 1..48 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P04191" 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:0000250|UniProtKB:P04191" 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:0000250|UniProtKB:P04191" 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:0000250|UniProtKB:P04191" FT TRANSMEM 296..313 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 314..757 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TRANSMEM 758..777 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 778..787 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TRANSMEM 788..808 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 809..828 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TRANSMEM 829..851 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 852..897 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TRANSMEM 898..917 FT /note="Helical; Name=8" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 918..930 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TRANSMEM 931..949 FT /note="Helical; Name=9" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 950..964 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TRANSMEM 965..985 FT /note="Helical; Name=10" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 986..999 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P04191" FT REGION 370..400 FT /note="Interaction with phospholamban 1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT REGION 788..808 FT /note="Interaction with phospholamban 2" 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="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 305 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 307 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 309 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 351 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 353 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 353 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 442 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 489 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 515 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 560 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:P04191" FT BINDING 627 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 678 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 684 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 703 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 706 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 768 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 771 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 796 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 799 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 800 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 800 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 908 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:Q93084" FT MOD_RES 17 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64518" FT MOD_RES 19 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q64518" FT MOD_RES 415 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q64518" FT MOD_RES 662 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q93084" FT VAR_SEQ 994..999 FT /note="EKKDLK -> GVLETFMQAWCKQPLPGPHTTRGWLPGCHFNGWEQTEEFVFI FT QERWTVSGLGPEKKARERLGLVSAAS (in isoform SERCA3BC)" FT /evidence="ECO:0000305" FT /id="VSP_060852" SQ SEQUENCE 999 AA; 109359 MW; 8A6AEE29021AA379 CRC64; MEEAHLLSAA DVLRRFSVTA EGGLTLEQVT DARERYGPNE LPTEEGKSLW ELVVEQFEDL LVRILLLAAL VSFVLAWFEE GEETTTAFVE PLVIMLILVA NAIVGVWQER NAESAIEALK EYEPEMGKVI RSDRKGVQRI RARDIVPGDI VEVAVGDKVP ADLRLIEIKS TTLRVDQSIL TGESVSVTKH TDAIPDPRAV NQDKKNMLFS GTNIASGKAL GVAVATGLHT ELGKIRSQMA AVEPERTPLQ RKLDEFGRQL SHAISVICVA VWVINIGHFA DPAHGGSWLR GAVYYFKIAV ALAVAAIPEG LPAVITTCLA LGTRRMARKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ MSVCRMFVVA EAEAGACRLH EFTISGTTYT PEGEVRQGEQ LVRCGQFDGL VELATICALC NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTDLK GLSRVERAGA CNSVIKQLMQ KEFTLEFSRD RKSMSVYCTP TRADPKAQGS KMFVKGAPES VIERCSSVRV GSRTVPLSAT SREHILAKIR DWGSGSHTLR CLALATRDTP PRKEDMQLDD CSQFVQYETG LTFVGCVGML DPPRPEVAAC ITRCSRAGIR VVMITGDNKG TAVAICRRLG IFGDTEDVLG KAYTGREFDD LSPEQQRQAC RTARCFARVE PAHKSRIVEN LQSFNEITAM TGDGVNDAPA LKKAEIGIAM GSGTAVAKSA AEMVLSDDNF ASIVAAVEEG RAIYNNMKQF IRYLISSNVG EVVCIFLTAI LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMEKL PRNPREALIS GWLFFRYLAI GVYVGLATVA AATWWFLYDA EGPQVTFHQL RNFLKCSEDN PLFAGIDCEV FESRFPTTMA LSVLVTIEMC NALNSVSENQ SLLRMPPWLN PWLLGAVVMS MALHFLILLV PPLPLIFQVT PLSGRQWGVV LQMSLPVILL DEALKYLSRH HVDEKKDLK //