AT2A1_MAKNI
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 03-AUG-2022, entry version 143.
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=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:P04191};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
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).
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}.
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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 PRIDE; 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:0016021; C:integral component of membrane; 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 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 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..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
