UniProtKB - Q64578 (AT2A1_RAT)
Protein
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
Gene
Atp2a1
Organism
Rattus norvegicus (Rat)
Status
Functioni
Key regulator of striated muscle performance by acting as the major Ca2+ ATPase responsible for the reuptake of cytosolic Ca2+ into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.By similarity
Catalytic activityi
- EC:7.2.2.10By similarity
Activity regulationi
Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 304 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 305 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 307 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 309 | Calcium 1By similarity | 1 | |
Active sitei | 351 | 4-aspartylphosphate intermediateBy similarity | 1 | |
Metal bindingi | 351 | MagnesiumBy similarity | 1 | |
Metal bindingi | 353 | Magnesium; via carbonyl oxygenBy similarity | 1 | |
Binding sitei | 353 | ATPBy similarity | 1 | |
Binding sitei | 442 | ATPBy similarity | 1 | |
Binding sitei | 489 | ATPBy similarity | 1 | |
Binding sitei | 515 | ATPBy similarity | 1 | |
Binding sitei | 560 | ATPBy similarity | 1 | |
Binding sitei | 678 | ATPBy similarity | 1 | |
Binding sitei | 684 | ATPBy similarity | 1 | |
Metal bindingi | 703 | MagnesiumBy similarity | 1 | |
Binding sitei | 706 | ATPBy similarity | 1 | |
Metal bindingi | 768 | Calcium 2By similarity | 1 | |
Metal bindingi | 771 | Calcium 2By similarity | 1 | |
Metal bindingi | 796 | Calcium 1By similarity | 1 | |
Metal bindingi | 799 | Calcium 2By similarity | 1 | |
Metal bindingi | 800 | Calcium 1By similarity | 1 | |
Metal bindingi | 800 | Calcium 2By similarity | 1 | |
Metal bindingi | 908 | Calcium 2By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 625 – 627 | ATPBy similarity | 3 |
GO - Molecular functioni
- ATPase activity Source: UniProtKB
- ATP binding Source: RGD
- calcium-dependent ATPase activity Source: ARUK-UCL
- calcium ion binding Source: RGD
- calcium transmembrane transporter activity, phosphorylative mechanism Source: ARUK-UCL
- nucleotide-sugar transmembrane transporter activity Source: RGD
- protein homodimerization activity Source: RGD
- proton-exporting ATPase activity, phosphorylative mechanism Source: GO_Central
GO - Biological processi
- apoptotic mitochondrial changes Source: RGD
- calcium ion import Source: RGD
- calcium ion import into sarcoplasmic reticulum Source: UniProtKB
- calcium ion transmembrane transport Source: ARUK-UCL
- calcium ion transport Source: RGD
- cellular calcium ion homeostasis Source: GO_Central
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: RGD
- maintenance of mitochondrion location Source: RGD
- negative regulation of endoplasmic reticulum calcium ion concentration Source: RGD
- negative regulation of striated muscle contraction Source: UniProtKB
- positive regulation of ATPase-coupled calcium transmembrane transporter activity Source: UniProtKB
- positive regulation of calcium ion import into sarcoplasmic reticulum Source: UniProtKB
- positive regulation of cardiac muscle cell contraction Source: UniProtKB
- positive regulation of endoplasmic reticulum calcium ion concentration Source: RGD
- positive regulation of fast-twitch skeletal muscle fiber contraction Source: UniProtKB
- positive regulation of mitochondrial calcium ion concentration Source: RGD
- regulation of muscle contraction Source: RGD
- regulation of striated muscle contraction Source: UniProtKB
- relaxation of skeletal muscle Source: RGD
- response to endoplasmic reticulum stress Source: RGD
- response to peptide hormone Source: UniProtKB
- sarcoplasmic reticulum calcium ion transport Source: RGD
Keywordsi
Molecular function | Translocase |
Biological process | Calcium transport, Ion transport, Transport |
Ligand | ATP-binding, Calcium, Magnesium, Metal-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (EC:7.2.2.10By similarity)Short name: SERCA1 Short name: SR Ca(2+)-ATPase 1 Alternative name(s): Calcium pump 1 Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform Endoplasmic reticulum class 1/2 Ca(2+) ATPase |
Gene namesi | Name:Atp2a1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 621293, Atp2a1 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
Other locations
- Sarcoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB
- sarcoplasmic reticulum Source: RGD
- sarcoplasmic reticulum membrane Source: UniProtKB
Mitochondrion
- mitochondrion Source: GOC
Other locations
- endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
- H zone Source: UniProtKB
- I band Source: UniProtKB
- integral component of membrane Source: UniProtKB
- intracellular membrane-bounded organelle Source: RGD
- membrane Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 48 | CytoplasmicCuratedAdd BLAST | 48 | |
Transmembranei | 49 – 69 | Helical; Name=1By similarityAdd BLAST | 21 | |
Topological domaini | 70 – 89 | LumenalCuratedAdd BLAST | 20 | |
Transmembranei | 90 – 110 | Helical; Name=2By similarityAdd BLAST | 21 | |
Topological domaini | 111 – 253 | CytoplasmicCuratedAdd BLAST | 143 | |
Transmembranei | 254 – 273 | Helical; Name=3By similarityAdd BLAST | 20 | |
Topological domaini | 274 – 295 | LumenalCuratedAdd BLAST | 22 | |
Transmembranei | 296 – 313 | Helical; Name=4By similarityAdd BLAST | 18 | |
Topological domaini | 314 – 757 | CytoplasmicCuratedAdd BLAST | 444 | |
Transmembranei | 758 – 777 | Helical; Name=5By similarityAdd BLAST | 20 | |
Topological domaini | 778 – 787 | LumenalCurated | 10 | |
Transmembranei | 788 – 808 | Helical; Name=6By similarityAdd BLAST | 21 | |
Topological domaini | 809 – 828 | CytoplasmicCuratedAdd BLAST | 20 | |
Transmembranei | 829 – 851 | Helical; Name=7By similarityAdd BLAST | 23 | |
Topological domaini | 852 – 897 | LumenalCuratedAdd BLAST | 46 | |
Transmembranei | 898 – 917 | Helical; Name=8By similarityAdd BLAST | 20 | |
Topological domaini | 918 – 930 | CytoplasmicCuratedAdd BLAST | 13 | |
Transmembranei | 931 – 949 | Helical; Name=9By similarityAdd BLAST | 19 | |
Topological domaini | 950 – 964 | LumenalCuratedAdd BLAST | 15 | |
Transmembranei | 965 – 985 | Helical; Name=10By similarityAdd BLAST | 21 | |
Topological domaini | 986 – 994 | CytoplasmicCurated | 9 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, Sarcoplasmic reticulumPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000046190 | 1 – 994 | Sarcoplasmic/endoplasmic reticulum calcium ATPase 1Add BLAST | 994 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 441 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 569 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 581 | PhosphoserineCombined sources | 1 | |
Modified residuei | 643 | PhosphoserineCombined sources | 1 | |
Disulfide bondi | 876 ↔ 888 | By similarity |
Keywords - PTMi
Disulfide bond, PhosphoproteinProteomic databases
jPOSTi | Q64578 |
PRIDEi | Q64578 |
PTM databases
iPTMneti | Q64578 |
PhosphoSitePlusi | Q64578 |
SwissPalmi | Q64578 |
Expressioni
Tissue specificityi
Skeletal muscle, fast twitch muscle (type II) fibers.1 Publication
Inductioni
Increased contractile activity leads to a decrease in SERCA1 expression, while decreased contractile activity leads to an increase in SERCA1 expression.1 Publication
Interactioni
Subunit structurei
Interacts with sarcolipin (SLN) (By similarity).
Interacts with phospholamban (PLN) (By similarity).
Interacts with myoregulin (MRLN).
Interacts with DWORF (By similarity).
By similarityGO - Molecular functioni
- protein homodimerization activity Source: RGD
Protein-protein interaction databases
BioGRIDi | 250515, 1 interactor |
STRINGi | 10116.ENSRNOP00000067246 |
Chemistry databases
BindingDBi | Q64578 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 788 – 808 | Interaction with PLNBy similarityAdd BLAST | 21 | |
Regioni | 932 – 943 | Interaction with PLNBy similarityAdd BLAST | 12 |
Domaini
Ca2+ and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca2+ binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca2+ ions to the lumenal side and promotes Ca2+ release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation.By similarity
PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices.By similarity
Sequence similaritiesi
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily. [View classification]Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0202, Eukaryota |
InParanoidi | Q64578 |
OrthoDBi | 100699at2759 |
PhylomeDBi | Q64578 |
Family and domain databases
Gene3Di | 3.40.1110.10, 1 hit 3.40.50.1000, 1 hit |
InterProi | View protein in InterPro IPR006068, ATPase_P-typ_cation-transptr_C IPR004014, ATPase_P-typ_cation-transptr_N IPR023299, ATPase_P-typ_cyto_dom_N IPR018303, ATPase_P-typ_P_site IPR023298, ATPase_P-typ_TM_dom_sf IPR008250, ATPase_P-typ_transduc_dom_A_sf IPR036412, HAD-like_sf IPR023214, HAD_sf IPR005782, P-type_ATPase_IIA IPR001757, P_typ_ATPase IPR030332, SERCA1/2 |
PANTHERi | PTHR42861:SF18, PTHR42861:SF18, 1 hit |
Pfami | View protein in Pfam PF00689, Cation_ATPase_C, 1 hit PF00690, Cation_ATPase_N, 1 hit |
PRINTSi | PR00120, HATPASE |
SMARTi | View protein in SMART SM00831, Cation_ATPase_N, 1 hit |
SUPFAMi | SSF56784, SSF56784, 1 hit SSF81653, SSF81653, 1 hit SSF81660, SSF81660, 1 hit SSF81665, SSF81665, 1 hit |
TIGRFAMsi | TIGR01116, ATPase-IIA1_Ca, 1 hit TIGR01494, ATPase_P-type, 3 hits |
PROSITEi | View protein in PROSITE PS00154, ATPASE_E1_E2, 1 hit |
i Sequence
Sequence statusi: Complete.
Q64578-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEAAHSKSTE ECLSYFGVSE TTGLTPDQVK RHLEKYGPNE LPAEEGKSLW
60 70 80 90 100
ELVVEQFEDL LVRILLLAAC ISFVLAWFEE GEETVTAFVE PFVILLILIA
110 120 130 140 150
NAIVGVWQER NAENAIEALK EYEPEMGKVY RADRKSVQRI KARDIVPGDI
160 170 180 190 200
VEVAVGDKVP ADIRILSIKS TTLRVDQSIL TGESVSVIKH TDPVPDPRAV
210 220 230 240 250
NQDKKNMLFS GTNIAAGKAV GIVATTGVST EIGKIRDQMA ATEQDKTPLQ
260 270 280 290 300
QKLDEFGEQL SKVISLICVA VWLINIGHFN DPVHGGSWFR GAIYYFKIAV
310 320 330 340 350
ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS
360 370 380 390 400
DKTGTLTTNQ MSVCKMFIID KVDGDICSLN EFSITGSTYA PEGEVLKNDK
410 420 430 440 450
PVRAGQYDGL VELATICALC NDSSLDFNET KGVYEKVGEA TETALTTLVE
460 470 480 490 500
KMNVFNTEVR SLSKVERANA CNSVIRQLMK KEFTLEFSRD RKSMSVYCSP
510 520 530 540 550
AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPLTGP VKEKIMSVIK
560 570 580 590 600
EWGTGRDTLR CLALATRDTP PKREEMVLDD SAKFMEYEMD LTFVGVVGML
610 620 630 640 650
DPPRKEVTGS IQLCRDAGIR VIMITGDNKG TAIAICRRIG IFSENEEVAD
660 670 680 690 700
RAYTGREFDD LPLAEQREAC RRACCFARVE PSHKSKIVEY LQSYDEITAM
710 720 730 740 750
TGDGVNDAPA LKKAEIGIAM GSGTAVAKTA SEMVLADDNF STIVAAVEEG
760 770 780 790 800
RAIYNNMKQF IRYLISSNVG EVVCIFLTAA LGLPEALIPV QLLWVNLVTD
810 820 830 840 850
GLPATALGFN PPDLDIMDRP PRSPKEPLIS GWLFFRYMAI GGYVGAATVG
860 870 880 890 900
AAAWWFLYAE DGPHVSYHQL THFMQCTEHN PEFDGLDCEV FEAPEPMTMA
910 920 930 940 950
LSVLVTIEMC NALNSLSENQ SLLRMPPWVN IWLLGSICLS MSLHFLILYV
960 970 980 990
DPLPMIFKLR ALDFTQWLMV LKISLPVIGL DELLKFIARN YLEG
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M99223 mRNA Translation: AAA40991.1 AF091853 Genomic DNA Translation: AAD17802.1 AF091852 Genomic DNA Translation: AAD17801.1 |
PIRi | A48849 |
RefSeqi | NP_478120.1, NM_058213.1 |
Genome annotation databases
GeneIDi | 116601 |
KEGGi | rno:116601 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M99223 mRNA Translation: AAA40991.1 AF091853 Genomic DNA Translation: AAD17802.1 AF091852 Genomic DNA Translation: AAD17801.1 |
PIRi | A48849 |
RefSeqi | NP_478120.1, NM_058213.1 |
3D structure databases
SMRi | Q64578 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 250515, 1 interactor |
STRINGi | 10116.ENSRNOP00000067246 |
Chemistry databases
BindingDBi | Q64578 |
ChEMBLi | CHEMBL3585236 |
DrugCentrali | Q64578 |
PTM databases
iPTMneti | Q64578 |
PhosphoSitePlusi | Q64578 |
SwissPalmi | Q64578 |
Proteomic databases
jPOSTi | Q64578 |
PRIDEi | Q64578 |
Genome annotation databases
GeneIDi | 116601 |
KEGGi | rno:116601 |
Organism-specific databases
CTDi | 487 |
RGDi | 621293, Atp2a1 |
Phylogenomic databases
eggNOGi | KOG0202, Eukaryota |
InParanoidi | Q64578 |
OrthoDBi | 100699at2759 |
PhylomeDBi | Q64578 |
Miscellaneous databases
PROi | PR:Q64578 |
Family and domain databases
Gene3Di | 3.40.1110.10, 1 hit 3.40.50.1000, 1 hit |
InterProi | View protein in InterPro IPR006068, ATPase_P-typ_cation-transptr_C IPR004014, ATPase_P-typ_cation-transptr_N IPR023299, ATPase_P-typ_cyto_dom_N IPR018303, ATPase_P-typ_P_site IPR023298, ATPase_P-typ_TM_dom_sf IPR008250, ATPase_P-typ_transduc_dom_A_sf IPR036412, HAD-like_sf IPR023214, HAD_sf IPR005782, P-type_ATPase_IIA IPR001757, P_typ_ATPase IPR030332, SERCA1/2 |
PANTHERi | PTHR42861:SF18, PTHR42861:SF18, 1 hit |
Pfami | View protein in Pfam PF00689, Cation_ATPase_C, 1 hit PF00690, Cation_ATPase_N, 1 hit |
PRINTSi | PR00120, HATPASE |
SMARTi | View protein in SMART SM00831, Cation_ATPase_N, 1 hit |
SUPFAMi | SSF56784, SSF56784, 1 hit SSF81653, SSF81653, 1 hit SSF81660, SSF81660, 1 hit SSF81665, SSF81665, 1 hit |
TIGRFAMsi | TIGR01116, ATPase-IIA1_Ca, 1 hit TIGR01494, ATPase_P-type, 3 hits |
PROSITEi | View protein in PROSITE PS00154, ATPASE_E1_E2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | AT2A1_RAT | |
Accessioni | Q64578Primary (citable) accession number: Q64578 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | November 1, 1996 | |
Last modified: | December 2, 2020 | |
This is version 177 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families