ID AT2A1_MAKNI Reviewed; 996 AA. AC P70083; P70084; Q91100; Q92082; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 04-NOV-2026, entry version 154. DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 1; DE Short=SERCA1; DE Short=SR Ca(2+)-ATPase 1; DE EC=7.2.2.10 {ECO:0000250|UniProtKB:P04191}; DE AltName: Full=Calcium pump 1; DE AltName: Full=Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform; DE AltName: Full=Endoplasmic reticulum class 1/2 Ca(2+) ATPase; GN Name=atp2a1; OS Makaira nigricans (Atlantic blue marlin). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata; OC Carangaria; Istiophoriformes; Makaira. OX NCBI_TaxID=13604; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SERCA1A AND SERCA1B). RC TISSUE=Extraocular muscle; RX PubMed=11079376; DOI=10.1016/s0305-0491(00)00256-x; RA Londraville R.L., Cramer T.D., Franck J.P.C.F., Tullis A., Block B.A.; RT "Cloning of a neonatal calcium atpase isoform (SERCA 1B) from extraocular RT muscle of adult blue marlin (Makaira nigricans)."; RL Comp. Biochem. Physiol. 127B:223-233(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 349-438 AND 448-578. RC TISSUE=Heating tissue, and Muscle; RX PubMed=8760229; DOI=10.1152/ajpregu.1996.271.1.r262; RA Tullis A., Block B.A.; RT "Expression of sarcoplasmic reticulum Ca(2+)-ATPase isoforms in marlin and RT swordfish muscle and heater cells."; RL Am. J. Physiol. 271:R262-R275(1996). CC -!- FUNCTION: Key regulator of striated muscle performance by acting as the CC major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) CC into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP CC coupled with the translocation of calcium from the cytosol to the CC sarcoplasmic reticulum lumen. Contributes to calcium sequestration CC involved in muscular excitation/contraction. CC {ECO:0000250|UniProtKB:Q8R429}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) + ATP + H2O = Ca(2+)(out) + ADP + phosphate + H(+); 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:P04191}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; CC Evidence={ECO:0000250|UniProtKB:P04191}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P04191}; CC -!- ACTIVITY REGULATION: Inhibited by sarcolipin (SLN) and myoregulin CC (MRLN). Also shown to be inhibited by phospholamban (PLN) in vitro. CC Enhanced by DWORF; DWORF increases activity by displacing sarcolipin CC (SLN), phospholamban (PLN) and myoregulin (MRLN). CC {ECO:0000250|UniProtKB:P04191, 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). CC {ECO:0000250|UniProtKB:Q8R429}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P04191}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P04191}. Sarcoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P04191}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P04191}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=SERCA1B; Synonyms=ATP2A1B; CC IsoId=P70083-1; Sequence=Displayed; CC Name=SERCA1A; Synonyms=ATP2A1A; CC IsoId=P70083-2; Sequence=VSP_000357; CC -!- DOMAIN: Ca(2+) and ATP binding cause major rearrangements of the CC cytoplasmic and transmembrane domains. According to the E1-E2 model, CC Ca(2+) binding to the cytosolic domain of the pump in the high-affinity CC E1 conformation is followed by the ATP-dependent phosphorylation of the CC active site Asp, giving rise to E1P. A conformational change of the CC phosphoenzyme gives rise to the low-affinity E2P state that exposes the CC Ca(2+) ions to the lumenal side and promotes Ca(2+) release. CC Dephosphorylation of the active site Asp mediates the subsequent return CC to the E1 conformation. {ECO:0000250|UniProtKB:P04191}. CC -!- DOMAIN: PLN and SLN both have a single transmembrane helix; both occupy CC a similar binding site on ATP2A1 that is situated between the ATP2A1 CC transmembrane helices. {ECO:0000250|UniProtKB:P04191}. 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; U65229; AAB08098.1; -; mRNA. DR EMBL; U65228; AAB08097.1; -; mRNA. DR EMBL; U58321; AAB17073.1; -; mRNA. DR EMBL; U58327; AAB17075.1; -; mRNA. DR AlphaFoldDB; P70083; -. DR SMR; P70083; -. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB. DR GO; GO:0031673; C:H zone; ISS:UniProtKB. DR GO; GO:0031674; C:I band; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0005388; F:P-type calcium transporter activity; ISS:UniProtKB. DR GO; GO:1990036; P:calcium ion import into sarcoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB. DR GO; GO:0045988; P:negative regulation of striated muscle contraction; ISS:UniProtKB. DR GO; GO:0031448; P:positive regulation of fast-twitch skeletal muscle fiber contraction; ISS:UniProtKB. DR GO; GO:0006942; P:regulation of striated muscle contraction; ISS:UniProtKB. DR CDD; cd02083; P-type_ATPase_SERCA; 1. DR FunFam; 3.40.1110.10:FF:000003; Calcium-transporting ATPase; 1. DR FunFam; 3.40.50.1000:FF:000005; Calcium-transporting ATPase 1; 1. DR FunFam; 1.20.1110.10:FF:000027; Calcium-transporting ATPase, putative; 1. DR FunFam; 1.20.1110.10:FF:000077; ECA1 (ER-TYPE CA2+-ATPASE 1); 1. DR FunFam; 1.20.1110.10:FF:000065; Sarcoplasmic/endoplasmic reticulum calcium ATPase 1; 1. DR FunFam; 2.70.150.10:FF:000160; Sarcoplasmic/endoplasmic reticulum calcium ATPase 1; 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; IPR059000; ATPase_P-type_domA. 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 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; PF08282; Hydrolase_3; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00120; HATPASE. DR SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 1. 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. PE 2: Evidence at transcript level; KW Alternative splicing; ATP-binding; Calcium; Calcium transport; KW Disulfide bond; Endoplasmic reticulum; Ion transport; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Sarcoplasmic reticulum; KW Translocase; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..996 FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 1" FT /id="PRO_0000046192" FT TOPO_DOM 1..48 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" 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:0000305" 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:0000305" 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:0000305" FT TRANSMEM 296..313 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 314..754 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 755..774 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 775..784 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 785..805 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 806..825 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 826..848 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 849..894 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 895..914 FT /note="Helical; Name=8" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 915..927 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 928..946 FT /note="Helical; Name=9" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 947..961 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 962..982 FT /note="Helical; Name=10" FT /evidence="ECO:0000250|UniProtKB:P04191" FT TOPO_DOM 983..996 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 785..805 FT /note="Interaction with PLN" FT /evidence="ECO:0000250|UniProtKB:P04191" FT REGION 929..940 FT /note="Interaction with PLN" 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="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 305 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 307 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 309 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" 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 512 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 557 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 622 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 623 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 624 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 675 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 681 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 700 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 703 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 765 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 768 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 793 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 797 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 797 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 905 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04191" FT DISULFID 873..885 FT /evidence="ECO:0000250|UniProtKB:P04191" FT VAR_SEQ 991..996 FT /note="TGKEVK -> K (in isoform SERCA1A)" FT /evidence="ECO:0000303|PubMed:11079376" FT /id="VSP_000357" FT CONFLICT 577 FT /note="D -> Y (in Ref. 1; AAB08097)" FT /evidence="ECO:0000305" SQ SEQUENCE 996 AA; 109247 MW; 821032E8D5F36392 CRC64; MENAHTKSPA ECLSYFGVNE HTGLSPDQFK KNLDKFGYNE LPAEEGKSIW DLIVEQFEDL LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA NAIVGVWQER NAEDAIEALK EYEPEMGKVY RSDRKSVQRI KAREIVPGDI VEVSVGDKVP ADIRIVSIKS TTLRVDQSIL TGESVSVIKH TESVPDPRAV NQDKKNMLFS GTNIAAGKAI GVAIATGVST EIGKIRDQMA ATEQEKTPLQ AKLDEFGEQL SKVISLICVA VWAINIGHFN DPVHGGSWIR GAVYYFKIAV ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ MCVTKMFIVK SVDGDHVDLN AFDISGSKYT PEGEVSHGGS KTNCSAYDGL VELATICALC NDSSLDYNES KKIYEKVGEA TETALCCLVE KMNVFNSNVK NLSRIERANA CCTVIKQLMK KNFTLEFSRD RKSMSVYCTP AKGDGGAKMF VKGAPEGVID RCAYVRVGTT RVPLTSAIKE KIMAVIRDWG TGRDTLRCLA LATRDTPLKV EEMNLEDSTK FADYETDMTF VGCVGMLDPP RKEVTGSIEL CRDAGIRVIM ITGDNKGTAI AICRRIGIFK EDEDVSNKAY TGREFDDLPS QDQAEAVRRA CCFARVEPSH KSKIVEFLQG NDDITAMTGD GVNDAPALKK AEIGIAMGSG TAVAKSASEM VLADDNFSSI VAAVEEGRAI YNNMKQFIRY LISSNVGEVV CIFLTAALGL PEALIPVQLL WVNLVTDGLP ATALGFNPPD LDIMGKPPRS PKEPLISGWL FFRYMAIGGY VGAATVGGAA WWFLYDSTGP AVTYYQLSHF MQCHNHNEDF TGVDCDIFEA SPPMTMALSV LVTIEMCNAL NSLSENQSLI RMPPWSNLWL MAAMTLSMSL HFMIIYVDPL PMIFKLTHLT FDQWLMVFKL SFPVILIDEV LKFFARNYIE TGKEVK //