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Protein

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Gene

Atp2a2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform SERCA2A is involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca2+ signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation.By similarity

Catalytic activityi

ATP + H2O + Ca2+(Side 1) = ADP + phosphate + Ca2+(Side 2).

Enzyme regulationi

Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi304Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi305Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi307Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi309Calcium 2By similarity1
Active sitei3514-aspartylphosphate intermediateBy similarity1
Metal bindingi702MagnesiumBy similarity1
Metal bindingi706MagnesiumBy similarity1
Metal bindingi767Calcium 1By similarity1
Metal bindingi770Calcium 1By similarity1
Metal bindingi795Calcium 2By similarity1
Metal bindingi798Calcium 1By similarity1
Metal bindingi799Calcium 1By similarity1
Metal bindingi799Calcium 2By similarity1
Metal bindingi907Calcium 1By similarity1

GO - Molecular functioni

  • ATP binding Source: RGD
  • calcium ion binding Source: RGD
  • calcium-transporting ATPase activity Source: RGD
  • calcium-transporting ATPase activity involved in regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  • lutropin-choriogonadotropic hormone receptor binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Calcium, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-418359. Reduction of cytosolic Ca++ levels.
R-RNO-5578775. Ion homeostasis.
R-RNO-936837. Ion transport by P-type ATPases.

Names & Taxonomyi

Protein namesi
Recommended name:
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (EC:3.6.3.8)
Short name:
SERCA2
Short name:
SR Ca(2+)-ATPase 2
Alternative name(s):
Calcium pump 2
Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform
Endoplasmic reticulum class 1/2 Ca(2+) ATPase
Gene namesi
Name:Atp2a2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 12

Organism-specific databases

RGDi2174. Atp2a2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 48CytoplasmicBy similarityAdd BLAST48
Transmembranei49 – 69Helical; Name=1By similarityAdd BLAST21
Topological domaini70 – 89LumenalBy similarityAdd BLAST20
Transmembranei90 – 110Helical; Name=2By similarityAdd BLAST21
Topological domaini111 – 253CytoplasmicBy similarityAdd BLAST143
Transmembranei254 – 273Helical; Name=3By similarityAdd BLAST20
Topological domaini274 – 295LumenalBy similarityAdd BLAST22
Transmembranei296 – 313Helical; Name=4By similarityAdd BLAST18
Topological domaini314 – 756CytoplasmicBy similarityAdd BLAST443
Transmembranei757 – 776Helical; Name=5By similarityAdd BLAST20
Topological domaini777 – 786LumenalBy similarity10
Transmembranei787 – 807Helical; Name=6By similarityAdd BLAST21
Topological domaini808 – 827CytoplasmicBy similarityAdd BLAST20
Transmembranei828 – 850Helical; Name=7By similarityAdd BLAST23
Topological domaini851 – 896LumenalBy similarityAdd BLAST46
Transmembranei897 – 916Helical; Name=8By similarityAdd BLAST20
Topological domaini917 – 929CytoplasmicBy similarityAdd BLAST13
Transmembranei930 – 948Helical; Name=9By similarityAdd BLAST19
Topological domaini949 – 963LumenalBy similarityAdd BLAST15
Transmembranei964 – 984Helical; Name=10By similarityAdd BLAST21
Topological domaini985 – 1043CytoplasmicBy similarityAdd BLAST59

GO - Cellular componenti

  • extrinsic component of cytoplasmic side of plasma membrane Source: RGD
  • integral component of plasma membrane Source: GO_Central
  • perinuclear region of cytoplasm Source: RGD
  • protein complex Source: RGD
  • ribbon synapse Source: Ensembl
  • sarcoplasmic reticulum Source: RGD
  • sarcoplasmic reticulum membrane Source: GO_Central
  • vesicle membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Sarcoplasmic reticulum

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3585237.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000462001 – 1043Sarcoplasmic/endoplasmic reticulum calcium ATPase 2Add BLAST1043

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38PhosphoserineCombined sources1
Modified residuei294Nitrated tyrosine2 Publications1
Modified residuei295Nitrated tyrosine2 Publications1
Modified residuei441PhosphothreonineBy similarity1
Modified residuei531PhosphoserineBy similarity1
Modified residuei580PhosphoserineBy similarity1
Modified residuei661PhosphoserineCombined sources1
Modified residuei663PhosphoserineCombined sources1

Post-translational modificationi

Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity.By similarity

Keywords - PTMi

Nitration, Phosphoprotein

Proteomic databases

PaxDbiP11507.
PeptideAtlasiP11507.
PRIDEiP11507.

PTM databases

iPTMnetiP11507.
PhosphoSitePlusiP11507.

Expressioni

Tissue specificityi

Isoform 2 is highly expressed in heart and slow twitch skeletal muscle. Isoform 1 is widely expressed.

Gene expression databases

ExpressionAtlasiP11507. baseline and differential.
GenevisibleiP11507. RN.

Interactioni

Subunit structurei

Interacts with sarcolipin (SLN) (By similarity). Interacts with phospholamban (PLN) (By similarity). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Isoform 1 interacts with TRAM2 (via C-terminus). Interacts with HAX1. Interacts with S100A8 and S100A9 (By similarity). Interacts with SLC35G1 and STIM1. Interacts with TMEM203. Interacts with TMEM64 and PDIA3 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Tlr9Q9EQU34EBI-916319,EBI-9979528From a different organism.

GO - Molecular functioni

  • lutropin-choriogonadotropic hormone receptor binding Source: RGD

Protein-protein interaction databases

BioGridi248313. 1 interactor.
IntActiP11507. 5 interactors.
MINTiMINT-4563897.
STRINGi10116.ENSRNOP00000024347.

Structurei

3D structure databases

ProteinModelPortaliP11507.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni370 – 400Interaction with phospholamban 1By similarityAdd BLAST31
Regioni575 – 594Interaction with HAX1By similarityAdd BLAST20
Regioni787 – 807Interaction with phospholamban 2By similarityAdd BLAST21
Regioni788 – 1043Interaction with TMEM64 and PDIA3By similarityAdd BLAST256

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0202. Eukaryota.
COG0474. LUCA.
GeneTreeiENSGT00850000132256.
HOGENOMiHOG000265621.
HOVERGENiHBG105648.
InParanoidiP11507.
KOiK05853.
OMAiDDMIFLG.
OrthoDBiEOG091G01LE.
PhylomeDBiP11507.

Family and domain databases

Gene3Di1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProiIPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR005782. P-type_ATPase_IIA.
IPR001757. P_typ_ATPase.
IPR030327. SERCA2.
[Graphical view]
PANTHERiPTHR24093:SF234. PTHR24093:SF234. 2 hits.
PfamiPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF08282. Hydrolase_3. 1 hit.
[Graphical view]
PRINTSiPR00120. HATPASE.
SMARTiSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 1 hit.
SSF81660. SSF81660. 1 hit.
TIGRFAMsiTIGR01116. ATPase-IIA1_Ca. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P11507-1) [UniParc]FASTAAdd to basket
Also known as: Atp2a2b, SERCA2b

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MENAHTKTVE EVLGHFGVNE STGLSLEQVK KLKERWGSNE LPAEEGKTLL
60 70 80 90 100
ELVIEQFEDL LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILVA
110 120 130 140 150
NAIVGVWQER NAENAIEALK EYEPEMGKVY RQDRKSVQRI KAKDIVPGDI
160 170 180 190 200
VEIAVGDKVP ADIRLTSIKS TTLRVDQSIL TGESVSVIKH TDPVPDPRAV
210 220 230 240 250
NQDKKNMLFS GTNIAAGKAM GVVVATGVNT EIGKIRDEMV ATEQERTPLQ
260 270 280 290 300
QKLDEFGEQL SKVISLICIA VWIINIGHFN DPVHGGSWIR GAIYYFKIAV
310 320 330 340 350
ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS
360 370 380 390 400
DKTGTLTTNQ MSVCRMFILD KVEGDTCSLN EFTITGSTYA PIGEVQKDDK
410 420 430 440 450
PVKCHQYDGL VELATICALC NDSALDYNEA KGVYEKVGEA TETALTCLVE
460 470 480 490 500
KMNVFDTELK GLSKIERANA CNSVIKQLMK KEFTLEFSRD RKSMSVYCTP
510 520 530 540 550
NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTPGV KQKIMSVIRE
560 570 580 590 600
WGSGSDTLRC LALATHDNPL RREEMHLEDS ANFIKYETNL TFVGCVGMLD
610 620 630 640 650
PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK
660 670 680 690 700
AFTGREFDEL SPSAQRDACL NARCFARVEP SHKSKIVEFL QSFDEITAMT
710 720 730 740 750
GDGVNDAPAL KKSEIGIAMG SGTAVAKTAS EMVLADDNFS TIVAAVEEGR
760 770 780 790 800
AIYNNMKQFI RYLISSNVGE VVCIFLTAAL GFPEALIPVQ LLWVNLVTDG
810 820 830 840 850
LPATALGFNP PDLDIMNKPP RNPKEPLISG WLFFRYLAIG CYVGAATVGA
860 870 880 890 900
AAWWFIAADG GPRVSFYQLS HFLQCKEDNP DFEGVDCAIF ESPYPMTMAL
910 920 930 940 950
SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE
960 970 980 990 1000
PLPLIFQITP LNLTQWLMVL KISLPVILMD ETLKFVARNY LEPGKECAQP
1010 1020 1030 1040
ATKPSCSLSA CTDGISWPFV LLIMPLVVWV YSTDTNFSDM FWS
Length:1,043
Mass (Da):114,768
Last modified:October 1, 1989 - v1
Checksum:i4B0B476BFD97F390
GO
Isoform 2 (identifier: P11507-2) [UniParc]FASTAAdd to basket
Also known as: Atp2a2a, SERCA2a

The sequence of this isoform differs from the canonical sequence as follows:
     994-1043: GKECAQPATKPSCSLSACTDGISWPFVLLIMPLVVWVYSTDTNFSDMFWS → AILE

Show »
Length:997
Mass (Da):109,681
Checksum:i3A14A6B604E97002
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000362994 – 1043GKECA…DMFWS → AILE in isoform 2. 2 PublicationsAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04022 mRNA. Translation: AAA40785.1.
J04024 mRNA. Translation: AAA40787.1.
J04023 mRNA. Translation: AAA40786.1.
X15635 mRNA. Translation: CAA33645.1.
PIRiA31982.
B31982.
RefSeqiNP_001103609.1. NM_001110139.2. [P11507-2]
NP_001104293.1. NM_001110823.2. [P11507-1]
UniGeneiRn.2305.

Genome annotation databases

EnsembliENSRNOT00000001738; ENSRNOP00000001738; ENSRNOG00000001285. [P11507-2]
ENSRNOT00000024347; ENSRNOP00000024347; ENSRNOG00000001285. [P11507-1]
GeneIDi29693.
KEGGirno:29693.
UCSCiRGD:2174. rat. [P11507-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04022 mRNA. Translation: AAA40785.1.
J04024 mRNA. Translation: AAA40787.1.
J04023 mRNA. Translation: AAA40786.1.
X15635 mRNA. Translation: CAA33645.1.
PIRiA31982.
B31982.
RefSeqiNP_001103609.1. NM_001110139.2. [P11507-2]
NP_001104293.1. NM_001110823.2. [P11507-1]
UniGeneiRn.2305.

3D structure databases

ProteinModelPortaliP11507.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248313. 1 interactor.
IntActiP11507. 5 interactors.
MINTiMINT-4563897.
STRINGi10116.ENSRNOP00000024347.

Chemistry databases

ChEMBLiCHEMBL3585237.

PTM databases

iPTMnetiP11507.
PhosphoSitePlusiP11507.

Proteomic databases

PaxDbiP11507.
PeptideAtlasiP11507.
PRIDEiP11507.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001738; ENSRNOP00000001738; ENSRNOG00000001285. [P11507-2]
ENSRNOT00000024347; ENSRNOP00000024347; ENSRNOG00000001285. [P11507-1]
GeneIDi29693.
KEGGirno:29693.
UCSCiRGD:2174. rat. [P11507-1]

Organism-specific databases

CTDi488.
RGDi2174. Atp2a2.

Phylogenomic databases

eggNOGiKOG0202. Eukaryota.
COG0474. LUCA.
GeneTreeiENSGT00850000132256.
HOGENOMiHOG000265621.
HOVERGENiHBG105648.
InParanoidiP11507.
KOiK05853.
OMAiDDMIFLG.
OrthoDBiEOG091G01LE.
PhylomeDBiP11507.

Enzyme and pathway databases

ReactomeiR-RNO-418359. Reduction of cytosolic Ca++ levels.
R-RNO-5578775. Ion homeostasis.
R-RNO-936837. Ion transport by P-type ATPases.

Miscellaneous databases

PROiP11507.

Gene expression databases

ExpressionAtlasiP11507. baseline and differential.
GenevisibleiP11507. RN.

Family and domain databases

Gene3Di1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProiIPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR005782. P-type_ATPase_IIA.
IPR001757. P_typ_ATPase.
IPR030327. SERCA2.
[Graphical view]
PANTHERiPTHR24093:SF234. PTHR24093:SF234. 2 hits.
PfamiPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF08282. Hydrolase_3. 1 hit.
[Graphical view]
PRINTSiPR00120. HATPASE.
SMARTiSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 1 hit.
SSF81660. SSF81660. 1 hit.
TIGRFAMsiTIGR01116. ATPase-IIA1_Ca. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAT2A2_RAT
AccessioniPrimary (citable) accession number: P11507
Secondary accession number(s): P11508
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: November 30, 2016
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.