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Protein

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Gene

Atp2a2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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).

Activity 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

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processCalcium transport, Ion transport, Transport
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 12

Organism-specific databases

RGDi2174 Atp2a2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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

CarbonylDBiP11507
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

BgeeiENSRNOG00000001285 Expressed in 10 organ(s), highest expression level in heart
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 Mus musculus.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248313, 2 interactors
CORUMiP11507
IntActiP11507, 7 interactors
MINTiP11507
STRINGi10116.ENSRNOP00000024347

Chemistry databases

BindingDBiP11507

Structurei

3D structure databases

ProteinModelPortaliP11507
SMRiP11507
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
GeneTreeiENSGT00890000139334
HOGENOMiHOG000265621
HOVERGENiHBG105648
InParanoidiP11507
KOiK05853
OMAiDPPTPLW
OrthoDBiEOG091G01LE
PhylomeDBiP11507

Family and domain databases

Gene3Di3.40.1110.10, 1 hit
3.40.50.1000, 1 hit
InterProiView 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
PANTHERiPTHR42861:SF18 PTHR42861:SF18, 1 hit
PfamiView protein in Pfam
PF00689 Cation_ATPase_C, 1 hit
PF00690 Cation_ATPase_N, 1 hit
PRINTSiPR00120 HATPASE
SMARTiView protein in SMART
SM00831 Cation_ATPase_N, 1 hit
SUPFAMiSSF56784 SSF56784, 1 hit
SSF81653 SSF81653, 1 hit
SSF81660 SSF81660, 1 hit
SSF81665 SSF81665, 1 hit
TIGRFAMsiTIGR01116 ATPase-IIA1_Ca, 1 hit
TIGR01494 ATPase_P-type, 2 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit

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

Similar proteinsi

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
SMRiP11507
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248313, 2 interactors
CORUMiP11507
IntActiP11507, 7 interactors
MINTiP11507
STRINGi10116.ENSRNOP00000024347

Chemistry databases

BindingDBiP11507
ChEMBLiCHEMBL3585237

PTM databases

CarbonylDBiP11507
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
GeneTreeiENSGT00890000139334
HOGENOMiHOG000265621
HOVERGENiHBG105648
InParanoidiP11507
KOiK05853
OMAiDPPTPLW
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

PROiPR:P11507

Gene expression databases

BgeeiENSRNOG00000001285 Expressed in 10 organ(s), highest expression level in heart
GenevisibleiP11507 RN

Family and domain databases

Gene3Di3.40.1110.10, 1 hit
3.40.50.1000, 1 hit
InterProiView 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
PANTHERiPTHR42861:SF18 PTHR42861:SF18, 1 hit
PfamiView protein in Pfam
PF00689 Cation_ATPase_C, 1 hit
PF00690 Cation_ATPase_N, 1 hit
PRINTSiPR00120 HATPASE
SMARTiView protein in SMART
SM00831 Cation_ATPase_N, 1 hit
SUPFAMiSSF56784 SSF56784, 1 hit
SSF81653 SSF81653, 1 hit
SSF81660 SSF81660, 1 hit
SSF81665 SSF81665, 1 hit
TIGRFAMsiTIGR01116 ATPase-IIA1_Ca, 1 hit
TIGR01494 ATPase_P-type, 2 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAT2A2_RAT
AccessioniPrimary (citable) accession number: P11507
Secondary accession number(s): P11508
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: November 7, 2018
This is version 180 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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