AT2A3_RAT
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 03-AUG-2022, entry version 180.
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 -!- 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=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}.
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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; P18596; -.
DR PRIDE; P18596; -.
DR GeneID; 25391; -.
DR KEGG; rno:25391; -.
DR CTD; 489; -.
DR RGD; 2175; Atp2a3.
DR eggNOG; KOG0202; Eukaryota.
DR InParanoid; P18596; -.
DR OrthoDB; 100699at2759; -.
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:0016021; C:integral component of membrane; IBA:GO_Central.
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:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; 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:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IDA:RGD.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISO:RGD.
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_0000046205"
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: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
