ID AT2A3_HUMAN Reviewed; 999 AA. AC Q93084; A8MZG0; D3DTJ8; O60900; O60901; O75501; O75502; Q16115; Q6JHX1; AC Q8TEX5; Q8TEX6; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 02-DEC-2020, sequence version 3. DT 27-MAR-2024, entry version 219. DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 {ECO:0000305}; DE Short=SERCA3; DE Short=SR Ca(2+)-ATPase 3; DE EC=7.2.2.10 {ECO:0000269|PubMed:15028735}; DE AltName: Full=Calcium pump 3; GN Name=ATP2A3 {ECO:0000312|HGNC:HGNC:813}; 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] (ISOFORM SERCA3A). RC TISSUE=Leukemic T-cell; RX PubMed=8809064; DOI=10.1042/bj3180689; RA Dode L., Wuytack F., Kools P.F.J., Baba-Aissa F., Raeymaekers L., Brik F., RA van de Ven W.J.M., Casteels R.; RT "cDNA cloning, expression and chromosomal localization of the human RT sarco/endoplasmic reticulum Ca(2+)-ATPase 3 gene."; RL Biochem. J. 318:689-699(1996). RN [2] RP ERRATUM OF PUBMED:8809064. RA Dode L., Wuytack F., Kools P.F.J., Baba-Aissa F., Raeymaekers L., Brik F., RA van de Ven W.J.M., Casteels R.; RL Biochem. J. 319:1008-1008(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS SERCA3B AND SERCA3C). RX PubMed=9593748; DOI=10.1074/jbc.273.22.13982; RA Dode L., De Greef C., Mountian I., Attard M., Town M.M., Casteels R., RA Wuytack F.; RT "Structure of the human sarco/endoplasmic reticulum Ca2+-ATPase 3 gene. RT Promoter analysis and alternative splicing of the SERCA3 pre-mRNA."; RL J. Biol. Chem. 273:13982-13994(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SERCA3A; SERCA3C AND SERCA3G). RC TISSUE=Kidney, and Leukemic T-cell; RX PubMed=9843705; DOI=10.1152/ajpcell.1998.275.6.c1449; RA Poch E., Leach S., Snape S., Cacic T., McLennan D.H., Lytton J.; RT "Functional characterization of alternatively spliced human SERCA3 RT transcripts."; RL Am. J. Physiol. 275:C1449-C1458(1998). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SERCA3A). RC TISSUE=Ovary; 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 [8] RP PROTEIN SEQUENCE OF 1-14, AND ACETYLATION AT MET-1. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [9] RP PROTEIN SEQUENCE OF 1-33; 111-120; 219-234; 482-489; 516-524; 549-560 AND RP 657-667, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Platelet; RA Bienvenut W.V., Claeys D.; RL Submitted (NOV-2005) to UniProtKB. RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 454-509. RX PubMed=8288608; DOI=10.1016/s0021-9258(17)42273-3; RA Wuytack F., Papp B., Verboomen H., Raeymaekers L., Dode L., Bobe R., RA Enouf J., Bokkala S., Authi K.S., Casteels R.; RT "A sarco/endoplasmic reticulum Ca(2+)-ATPase 3-type Ca2+ pump is expressed RT in platelets, in lymphoid cells, and in mast cells."; RL J. Biol. Chem. 269:1410-1416(1994). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 892-999 (ISOFORMS SERCA3E AND SERCA3D), RP ALTERNATIVE SPLICING, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=11956212; DOI=10.1074/jbc.m202011200; RA Martin V., Bredoux R., Corvazier E., Van Gorp R., Kovacs T., Gelebart P., RA Enouf J.; RT "Three novel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 isoforms. RT Expression, regulation, and function of the membranes of the SERCA3 RT family."; RL J. Biol. Chem. 277:24442-24452(2002). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 892-999 (ISOFORM SERCA3F), ALTERNATIVE RP SPLICING, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CATALYTIC RP ACTIVITY. RX PubMed=15028735; DOI=10.1074/jbc.m314286200; RA Bobe R., Bredoux R., Corvazier E., Andersen J.P., Clausen J.D., Dode L., RA Kovacs T., Enouf J.; RT "Identification, expression, function, and localization of a novel (sixth) RT isoform of the human sarco/endoplasmic reticulum Ca2+ATPase 3 gene."; RL J. Biol. Chem. 279:24297-24306(2004). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [16] RP INTERACTION WITH VMP1. 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 [17] RP INTERACTION WITH TUNAR. RX PubMed=34513312; DOI=10.1016/j.omtn.2021.06.027; RA Li M., Shao F., Qian Q., Yu W., Zhang Z., Chen B., Su D., Guo Y., RA Phan A.V., Song L.S., Stephens S.B., Sebag J., Imai Y., Yang L., Cao H.; RT "A putative long noncoding RNA-encoded micropeptide maintains cellular RT homeostasis in pancreatic beta cells."; RL Mol. Ther. Nucleic Acids 26:307-320(2021). RN [18] RP VARIANT [LARGE SCALE ANALYSIS] HIS-674. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). 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:0000269|PubMed:11956212, CC ECO:0000269|PubMed:15028735}. 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:15028735}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; CC Evidence={ECO:0000269|PubMed:15028735}; 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 CC (PubMed:28890335). Interacts with TUNAR; the interaction occurs at low CC levels in low glucose conditions and is increased by high glucose CC levels (PubMed:34513312). {ECO:0000250|UniProtKB:P04191, CC ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:28890335, CC ECO:0000269|PubMed:34513312}. CC -!- INTERACTION: CC Q93084-2; P37173: TGFBR2; NbExp=3; IntAct=EBI-21505448, EBI-296151; CC -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000269|PubMed:15028735}; CC Multi-pass membrane protein {ECO:0000269|PubMed:15028735}. Endoplasmic CC reticulum membrane {ECO:0000269|PubMed:15028735}; Multi-pass membrane CC protein {ECO:0000269|PubMed:15028735}. Sarcoplasmic reticulum membrane CC {ECO:0000269|PubMed:15028735}; Multi-pass membrane protein CC {ECO:0000269|PubMed:15028735}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Comment=The same names have been attributed to different isoforms.; CC Name=SERCA3A; Synonyms=HuS3-II; CC IsoId=Q93084-2; Sequence=Displayed; CC Name=SERCA3B; CC IsoId=Q93084-1; Sequence=VSP_060845; CC Name=SERCA3C; Synonyms=HuS3-IV; CC IsoId=Q93084-3; Sequence=VSP_060847; CC Name=SERCA3G; Synonyms=HuS3-I; CC IsoId=Q93084-4; Sequence=VSP_060849; CC Name=SERCA3E; CC IsoId=Q93084-5; Sequence=VSP_060844; CC Name=SERCA3D; CC IsoId=Q93084-6; Sequence=VSP_060848; CC Name=SERCA3F; CC IsoId=Q93084-7; Sequence=VSP_060846; CC -!- TISSUE SPECIFICITY: Found in most tissues. Most abundant in thymus, CC trachea, salivary gland, spleen, bone marrow, lymph node, peripheral CC leukocytes, pancreas and colon. Also detected in fetal tissues. CC Expressed in cell lineages of hematopoietic, epithelial, or embryonic CC origin and also expressed in several cancer cell lines. CC {ECO:0000269|PubMed:11956212, ECO:0000269|PubMed:15028735}. 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; Z69881; CAA93737.1; -; mRNA. DR EMBL; Z69880; CAA93736.1; -; Genomic_DNA. DR EMBL; Y15724; CAA75739.1; -; Genomic_DNA. DR EMBL; Y15725; CAA75739.1; JOINED; Genomic_DNA. DR EMBL; Y15726; CAA75739.1; JOINED; Genomic_DNA. DR EMBL; Y15727; CAA75739.1; JOINED; Genomic_DNA. DR EMBL; Y15728; CAA75739.1; JOINED; Genomic_DNA. DR EMBL; Y15729; CAA75739.1; JOINED; Genomic_DNA. DR EMBL; Y15730; CAA75739.1; JOINED; Genomic_DNA. DR EMBL; Y15738; CAA75748.1; -; Genomic_DNA. DR EMBL; Y15737; CAA75747.1; -; Genomic_DNA. DR EMBL; AF068220; AAC24525.1; -; mRNA. DR EMBL; AF068221; AAC24526.1; -; mRNA. DR EMBL; AC005940; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90468.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90463.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90469.1; -; Genomic_DNA. DR EMBL; BC035729; AAH35729.1; -; mRNA. DR EMBL; S68239; AAB29700.1; -; mRNA. DR EMBL; AF458228; AAL78967.1; -; mRNA. DR EMBL; AF458229; AAL78968.1; -; mRNA. DR EMBL; AY460339; AAR15415.1; -; mRNA. DR CCDS; CCDS11041.1; -. [Q93084-1] DR CCDS; CCDS11042.1; -. [Q93084-5] DR CCDS; CCDS42234.1; -. [Q93084-3] DR CCDS; CCDS45579.1; -. [Q93084-2] DR CCDS; CCDS45580.1; -. [Q93084-4] DR PIR; I55399; I55399. DR PIR; S72267; S72267. DR RefSeq; NP_005164.2; NM_005173.3. [Q93084-2] DR RefSeq; NP_777613.1; NM_174953.2. [Q93084-5] DR RefSeq; NP_777614.1; NM_174954.2. [Q93084-6] DR RefSeq; NP_777615.1; NM_174955.2. [Q93084-1] DR RefSeq; NP_777616.1; NM_174956.2. [Q93084-3] DR RefSeq; NP_777617.1; NM_174957.2. [Q93084-4] DR RefSeq; NP_777618.1; NM_174958.2. [Q93084-3] DR AlphaFoldDB; Q93084; -. DR SMR; Q93084; -. DR BioGRID; 106979; 306. DR IntAct; Q93084; 52. DR MINT; Q93084; -. DR STRING; 9606.ENSP00000353072; -. DR BindingDB; Q93084; -. DR ChEMBL; CHEMBL2401; -. DR GlyGen; Q93084; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q93084; -. DR PhosphoSitePlus; Q93084; -. DR SwissPalm; Q93084; -. DR BioMuta; ATP2A3; -. DR DMDM; 19864659; -. DR EPD; Q93084; -. DR jPOST; Q93084; -. DR MassIVE; Q93084; -. DR MaxQB; Q93084; -. DR PaxDb; 9606-ENSP00000353072; -. DR PeptideAtlas; Q93084; -. DR ProteomicsDB; 75708; -. [Q93084-1] DR ProteomicsDB; 75709; -. [Q93084-2] DR ProteomicsDB; 75710; -. [Q93084-3] DR ProteomicsDB; 75711; -. [Q93084-4] DR ProteomicsDB; 75712; -. [Q93084-5] DR ProteomicsDB; 75713; -. [Q93084-6] DR ProteomicsDB; 75714; -. [Q93084-7] DR Pumba; Q93084; -. DR Antibodypedia; 1517; 174 antibodies from 29 providers. DR DNASU; 489; -. DR Ensembl; ENST00000309890.11; ENSP00000312577.7; ENSG00000074370.18. [Q93084-3] DR Ensembl; ENST00000352011.7; ENSP00000301387.6; ENSG00000074370.18. [Q93084-1] DR Ensembl; ENST00000359983.7; ENSP00000353072.3; ENSG00000074370.18. [Q93084-5] DR Ensembl; ENST00000397035.7; ENSP00000380229.3; ENSG00000074370.18. [Q93084-3] DR Ensembl; ENST00000397041.8; ENSP00000380234.3; ENSG00000074370.18. [Q93084-2] DR Ensembl; ENST00000397043.7; ENSP00000380236.3; ENSG00000074370.18. [Q93084-4] DR GeneID; 489; -. DR KEGG; hsa:489; -. DR MANE-Select; ENST00000397041.8; ENSP00000380234.3; NM_005173.4; NP_005164.2. DR UCSC; uc002fwx.3; human. [Q93084-2] DR AGR; HGNC:813; -. DR CTD; 489; -. DR DisGeNET; 489; -. DR GeneCards; ATP2A3; -. DR HGNC; HGNC:813; ATP2A3. DR HPA; ENSG00000074370; Tissue enhanced (lymphoid tissue, salivary gland). DR MIM; 601929; gene. DR neXtProt; NX_Q93084; -. DR OpenTargets; ENSG00000074370; -. DR PharmGKB; PA25106; -. DR VEuPathDB; HostDB:ENSG00000074370; -. DR eggNOG; KOG0202; Eukaryota. DR GeneTree; ENSGT00940000155668; -. DR HOGENOM; CLU_002360_3_2_1; -. DR InParanoid; Q93084; -. DR OMA; GIVDWGC; -. DR OrthoDB; 203629at2759; -. DR PhylomeDB; Q93084; -. DR TreeFam; TF300651; -. DR PathwayCommons; Q93084; -. 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; Q93084; -. DR SIGNOR; Q93084; -. DR BioGRID-ORCS; 489; 8 hits in 1157 CRISPR screens. DR ChiTaRS; ATP2A3; human. DR GeneWiki; ATP2A3; -. DR GenomeRNAi; 489; -. DR Pharos; Q93084; Tchem. DR PRO; PR:Q93084; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q93084; Protein. DR Bgee; ENSG00000074370; Expressed in granulocyte and 144 other cell types or tissues. DR ExpressionAtlas; Q93084; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031090; C:organelle membrane; IDA:ARUK-UCL. DR GO; GO:0031095; C:platelet dense tubular network membrane; TAS:Reactome. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB. 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: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; IDA:ARUK-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:ARUK-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:ARUK-UCL. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:ARUK-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:ARUK-UCL. DR GO; GO:0006816; P:calcium ion transport; TAS:UniProtKB. DR GO; GO:1903515; P:calcium ion transport from cytosol to endoplasmic reticulum; IDA:ARUK-UCL. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:ARUK-UCL. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:ARUK-UCL. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome. DR GO; GO:1900121; P:negative regulation of receptor binding; IMP:ARUK-UCL. DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. 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 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; Q93084; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Calcium; Calcium transport; KW Direct protein sequencing; Endoplasmic reticulum; Ion transport; Magnesium; KW Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Sarcoplasmic reticulum; Translocase; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..999 FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 3" FT /id="PRO_0000046202" 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:0000269|PubMed:12665801, ECO:0000269|Ref.9" 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 25 FT /note="Phosphoserine" 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:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 993 FT /note="H -> HACLYPGLLRTVSQAWSRQPLTTSWTPDHTGLASLGQGHSIVSLSEL FT LREGGSR (in isoform SERCA3E)" FT /evidence="ECO:0000305" FT /id="VSP_060844" FT VAR_SEQ 994..999 FT /note="EEMSQK -> ACLYPGLLRTVSQAWSRQPLTTSWTPDHTGRNEPEVSAGNRV FT ESPVCTSD (in isoform SERCA3B)" FT /evidence="ECO:0000305" FT /id="VSP_060845" FT VAR_SEQ 994..999 FT /note="EEMSQK -> GPGTQHRLAVRAAQRGRKQGRNEPEVSAGNRVESPVCTSD FT (in isoform SERCA3F)" FT /evidence="ECO:0000305" FT /id="VSP_060846" FT VAR_SEQ 994..998 FT /note="EEMSQ -> ACLYPGLLRTVSQAWSRQPLTTSWTPDHTGLASLK (in FT isoform SERCA3C)" FT /evidence="ECO:0000305" FT /id="VSP_060847" FT VAR_SEQ 994..998 FT /note="EEMSQ -> ACLYPGLLRTVSQAWSRQPLTTSWTPDHTGARDTASSRCQSCS FT EREEAGK (in isoform SERCA3D)" FT /evidence="ECO:0000305" FT /id="VSP_060848" FT VAR_SEQ 994 FT /note="Missing (in isoform SERCA3G)" FT /evidence="ECO:0000305" FT /id="VSP_060849" FT VARIANT 674 FT /note="R -> H (in a breast cancer sample; somatic mutation; FT dbSNP:rs144535413)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036498" FT VARIANT 869 FT /note="Q -> H (in dbSNP:rs11654827)" FT /id="VAR_048372" FT CONFLICT 673 FT /note="A -> T (in Ref. 4; AAC24525)" FT /evidence="ECO:0000305" FT CONFLICT 802 FT /note="L -> H (in Ref. 3; CAA75739)" FT /evidence="ECO:0000305" FT CONFLICT 817 FT /note="M -> I (in Ref. 1; CAA93737)" FT /evidence="ECO:0000305" SQ SEQUENCE 999 AA; 109256 MW; 44E9F1FBF41FE36A CRC64; MEAAHLLPAA DVLRHFSVTA EGGLSPAQVT GARERYGPNE LPSEEGKSLW ELVLEQFEDL LVRILLLAAL VSFVLAWFEE GEETTTAFVE PLVIMLILVA NAIVGVWQER NAESAIEALK EYEPEMGKVI RSDRKGVQRI RARDIVPGDI VEVAVGDKVP ADLRLIEIKS TTLRVDQSIL TGESVSVTKH TEAIPDPRAV NQDKKNMLFS GTNITSGKAV GVAVATGLHT ELGKIRSQMA AVEPERTPLQ RKLDEFGRQL SHAISVICVA VWVINIGHFA DPAHGGSWLR GAVYYFKIAV ALAVAAIPEG LPAVITTCLA LGTRRMARKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ MSVCRMFVVA EADAGSCLLH EFTISGTTYT PEGEVRQGDQ PVRCGQFDGL VELATICALC NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTDLQ ALSRVERAGA CNTVIKQLMR KEFTLEFSRD RKSMSVYCTP TRPHPTGQGS KMFVKGAPES VIERCSSVRV GSRTAPLTPT SREQILAKIR DWGSGSDTLR CLALATRDAP PRKEDMELDD CSKFVQYETD LTFVGCVGML DPPRPEVAAC ITRCYQAGIR VVMITGDNKG TAVAICRRLG IFGDTEDVAG KAYTGREFDD LSPEQQRQAC RTARCFARVE PAHKSRIVEN LQSFNEITAM TGDGVNDAPA LKKAEIGIAM GSGTAVAKSA AEMVLSDDNF ASIVAAVEEG RAIYSNMKQF IRYLISSNVG EVVCIFLTAI LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMEKL PRSPREALIS GWLFFRYLAI GVYVGLATVA AATWWFVYDA EGPHINFYQL RNFLKCSEDN PLFAGIDCEV FESRFPTTMA LSVLVTIEMC NALNSVSENQ SLLRMPPWMN PWLLVAVAMS MALHFLILLV PPLPLIFQVT PLSGRQWVVV LQISLPVILL DEALKYLSRN HMHEEMSQK //