AT2A3_HUMAN
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 03-AUG-2022, entry version 210.
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 -!- 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 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}.
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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; 303.
DR IntAct; Q93084; 52.
DR MINT; Q93084; -.
DR STRING; 9606.ENSP00000353072; -.
DR BindingDB; Q93084; -.
DR ChEMBL; CHEMBL2401; -.
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; Q93084; -.
DR PeptideAtlas; Q93084; -.
DR PRIDE; 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 Antibodypedia; 1517; 154 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 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; FISWDVV; -.
DR OrthoDB; 100699at2759; -.
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 1079 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 142 other tissues.
DR ExpressionAtlas; Q93084; baseline and differential.
DR Genevisible; Q93084; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
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:0015662; F:P-type ion transporter activity; IBA:GO_Central.
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:cellular 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:ion transmembrane transport; IBA:GO_Central.
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 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 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"
FT TRANSMEM 49..69
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 70..89
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 90..110
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 111..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 254..273
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 274..295
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 296..313
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 314..757
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 758..777
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 778..787
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 788..808
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 809..828
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 829..851
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 852..897
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 898..917
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250"
FT TOPO_DOM 918..930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 931..949
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250"
FT TOPO_DOM 950..964
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 965..985
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250"
FT TOPO_DOM 986..999
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
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 515
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 703
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 707
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
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
