AT2A3_MOUSE
ID AT2A3_MOUSE Reviewed; 999 AA.
AC Q64518; O70625; Q64517; Q8VD16;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 4.
DT 03-AUG-2022, entry version 184.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SERCA3A AND SERCA3B).
RC STRAIN=C57BL/6J;
RA Tokuyama Y., Chen X., Roe M.W., Bell G.I.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [4]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM SERCA3A), AND
RP ALTERNATIVE SPLICING.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; THR-19; SER-25 AND
RP THR-415, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 -!- 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 (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=3;
CC Name=SERCA3A;
CC IsoId=Q64518-2; Sequence=Displayed;
CC Name=SERCA3B;
CC IsoId=Q64518-1; Sequence=VSP_060850;
CC Name=SERCA3C;
CC IsoId=Q64518-3; Sequence=VSP_060851;
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; U49394; AAB04099.1; -; mRNA.
DR EMBL; U49393; AAB04098.1; -; mRNA.
DR EMBL; CH466596; EDL12704.1; -; Genomic_DNA.
DR EMBL; BC017639; AAH17639.1; -; mRNA.
DR EMBL; Y15734; CAA75744.1; -; Genomic_DNA.
DR EMBL; Y15735; CAA75744.1; JOINED; Genomic_DNA.
DR EMBL; Y15734; CAA75745.1; -; Genomic_DNA.
DR EMBL; Y15735; CAA75745.1; JOINED; Genomic_DNA.
DR EMBL; Y15734; CAA75743.1; -; Genomic_DNA.
DR EMBL; Y15735; CAA75743.1; JOINED; Genomic_DNA.
DR EMBL; Y15736; CAA75746.1; -; Genomic_DNA.
DR CCDS; CCDS24991.1; -. [Q64518-1]
DR CCDS; CCDS48843.1; -. [Q64518-2]
DR RefSeq; NP_001156808.1; NM_001163336.1. [Q64518-2]
DR RefSeq; NP_001156809.1; NM_001163337.1.
DR RefSeq; NP_058025.2; NM_016745.3. [Q64518-1]
DR AlphaFoldDB; Q64518; -.
DR SMR; Q64518; -.
DR BioGRID; 207277; 5.
DR IntAct; Q64518; 2.
DR MINT; Q64518; -.
DR STRING; 10090.ENSMUSP00000021142; -.
DR BindingDB; Q64518; -.
DR ChEMBL; CHEMBL4523338; -.
DR iPTMnet; Q64518; -.
DR PhosphoSitePlus; Q64518; -.
DR SwissPalm; Q64518; -.
DR EPD; Q64518; -.
DR jPOST; Q64518; -.
DR MaxQB; Q64518; -.
DR PaxDb; Q64518; -.
DR PRIDE; Q64518; -.
DR ProteomicsDB; 265125; -. [Q64518-2]
DR ProteomicsDB; 265126; -. [Q64518-2]
DR ProteomicsDB; 265127; -. [Q64518-3]
DR Antibodypedia; 1517; 154 antibodies from 29 providers.
DR DNASU; 53313; -.
DR Ensembl; ENSMUST00000021142; ENSMUSP00000021142; ENSMUSG00000020788. [Q64518-1]
DR Ensembl; ENSMUST00000108485; ENSMUSP00000104125; ENSMUSG00000020788. [Q64518-2]
DR GeneID; 53313; -.
DR KEGG; mmu:53313; -.
DR UCSC; uc007jzo.2; mouse. [Q64518-2]
DR CTD; 489; -.
DR MGI; MGI:1194503; Atp2a3.
DR VEuPathDB; HostDB:ENSMUSG00000020788; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000155668; -.
DR HOGENOM; CLU_002360_3_2_1; -.
DR InParanoid; Q64518; -.
DR OMA; FISWDVV; -.
DR PhylomeDB; Q64518; -.
DR TreeFam; TF300651; -.
DR Reactome; R-MMU-418359; Reduction of cytosolic Ca++ levels.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 53313; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Atp2a3; mouse.
DR PRO; PR:Q64518; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q64518; protein.
DR Bgee; ENSMUSG00000020788; Expressed in submandibular gland and 178 other tissues.
DR ExpressionAtlas; Q64518; baseline and differential.
DR Genevisible; Q64518; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0031090; C:organelle membrane; ISO:MGI.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0030899; F:calcium-dependent ATPase activity; ISO:MGI.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:P-type calcium transporter activity; ISO:MGI.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:1903515; P:calcium ion transport from cytosol to endoplasmic reticulum; ISO:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISO:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISO:MGI.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR005782; P-type_ATPase_IIA.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR 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 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_0000046203"
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:0000250|UniProtKB:Q93084"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 415
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q93084"
FT VAR_SEQ 994..999
FT /note="EKKDLK -> GVLGTFMQARSRQLPTTSRTPYHTGKKGPEVNPGSRGESPVW
FT PSD (in isoform SERCA3B)"
FT /evidence="ECO:0000305"
FT /id="VSP_060850"
FT VAR_SEQ 994..999
FT /note="EKKDLK -> GVLGTFMQARSRQLPTTSRTPYHTGLACKKKT (in
FT isoform SERCA3C)"
FT /evidence="ECO:0000305"
FT /id="VSP_060851"
FT CONFLICT 860
FT /note="T -> A (in Ref. 1; AAB04098/AAB04099)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 999 AA; 109530 MW; F64B7046E792B6E7 CRC64;
MEEAHLLSAA DVLRRFSVTA EGGLSLEQVT DARERYGPNE LPTEEGKSLW ELVVEQFEDL
LVRILLLAAL VSFVLAWFEE GEETTTAFVE PLVIMLILVA NAIVGVWQER NAESAIEALK
EYEPEMGKVI RSDRKGVQRI RARDIVPGDI VEVAVGDKVP ADLRLIEIKS TTLRVDQSIL
TGESVSVTKH TDAIPDPRAV NQDKKNMLFS GTNIASGKAL GVAVATGLQT ELGKIRSQMA
AVEPERTPLQ RKLDEFGRQL SHAISVICVA VWVINIGHFA DPAHGGSWLR GAVYYFKIAV
ALAVAAIPEG LPAVITTCLA LGTRRMARKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ
MSVCRMFVVA EAEAGTCRLH EFTISGTTYT PEGEVRQGEQ PVRCGQFDGL VELATICALC
NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTDLK GLSRVERAGA CNSVIKQLMR
KEFTLEFSRD RKSMSVYCTP TRADPKVQGS KMFVKGAPES VIERCSSVRV GSRTAPLSTT
SREHILAKIR DWGSGSDTLR CLALATRDTP PRKEDMHLDD CSRFVQYETD LTFVGCVGML
DPPRPEVAAC ITRCSRAGIR VVMITGDNKG TAVAICRRLG IFGDTEDVLG KAYTGREFDD
LSPEQQRQAC RTARCFARVE PAHKSRIVEN LQSFNEITAM TGDGVNDAPA LKKAEIGIAM
GSGTAVAKSA AEMVLSDDNF ASIVAAVEEG RAIYNNMKQF IRYLISSNVG EVVCIFLTAI
LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMEKP PRNPREALIS GWLFFRYLAI
GVYVGLATVA AATWWFLYDT EGPQVTFYQL RNFLKCSEDN PLFAGIDCKV FESRFPTTMA
LSVLVTIEMC NALNSVSENQ SLLRMPPWLN PWLLGAVVMS MALHFLILLV PPLPLIFQVT
PLSGRQWGVV LQMSLPVILL DEALKYLSRN HMDEKKDLK
