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O55143 (AT2A2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Short name=SERCA2
Short name=SR Ca(2+)-ATPase 2
EC=3.6.3.8
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 names
Name:Atp2a2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1044 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Catalytic activity

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

Enzyme regulation

Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN By similarity.

Subunit structure

Associated with phospholamban (PLN) By similarity. Isoform SERCA2B interacts with TRAM2 (via C-terminus). Interacts with HAX1 By similarity. Interacts with S100A8 and S100A9. Ref.4 Ref.8

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Sarcoplasmic reticulum membrane; Multi-pass membrane protein.

Tissue specificity

Isoform SERCA2A is highly expressed in heart and slow twitch skeletal muscle. Isoform SERCA2B is widely expressed.

Post-translational modification

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

Sequence similarities

Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily. [View classification]

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentEndoplasmic reticulum
Membrane
Sarcoplasmic reticulum
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Calcium
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionHydrolase
   PTMIsopeptide bond
Nitration
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processER-nucleus signaling pathway

Inferred from mutant phenotype PubMed 14561754. Source: MGI

cellular calcium ion homeostasis

Inferred from direct assay PubMed 9887021. Source: MGI

negative regulation of heart contraction

Inferred from genetic interaction PubMed 10555147. Source: MGI

regulation of muscle contraction

Traceable author statement PubMed 11784029. Source: MGI

regulation of the force of heart contraction

Inferred from genetic interaction PubMed 10555147. Source: MGI

   Cellular_componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 16407245. Source: MGI

sarcoplasmic reticulum

Inferred from direct assay PubMed 9038922. Source: MGI

sarcoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium-transporting ATPase activity

Inferred from direct assay PubMed 12756243PubMed 9887021. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform SERCA2B (identifier: O55143-1)

Also known as: ATP2A2B;

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.
Isoform SERCA2A (identifier: O55143-2)

Also known as: ATP2A2A;

The sequence of this isoform differs from the canonical sequence as follows:
     995-1044: GKECVQPATKSSCSLSACTDGISWPFVLLIMPLVVWVYSTDTNFSDMFWS → AILE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10441044Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
PRO_0000046197

Regions

Topological domain1 – 4848Cytoplasmic By similarity
Transmembrane49 – 6921Helical; Name=1; By similarity
Topological domain70 – 8920Lumenal By similarity
Transmembrane90 – 11021Helical; Name=2; By similarity
Topological domain111 – 253143Cytoplasmic By similarity
Transmembrane254 – 27320Helical; Name=3; By similarity
Topological domain274 – 29522Lumenal By similarity
Transmembrane296 – 31318Helical; Name=4; By similarity
Topological domain314 – 756443Cytoplasmic By similarity
Transmembrane757 – 77620Helical; Name=5; By similarity
Topological domain777 – 78610Lumenal By similarity
Transmembrane787 – 80721Helical; Name=6; By similarity
Topological domain808 – 82720Cytoplasmic By similarity
Transmembrane828 – 85023Helical; Name=7; By similarity
Topological domain851 – 89646Lumenal By similarity
Transmembrane897 – 91620Helical; Name=8; By similarity
Topological domain917 – 92913Cytoplasmic By similarity
Transmembrane930 – 94819Helical; Name=9; By similarity
Topological domain949 – 96315Lumenal By similarity
Transmembrane964 – 98421Helical; Name=10; By similarity
Topological domain985 – 104460Cytoplasmic By similarity
Region370 – 40031Interacts with phospholamban 1 By similarity
Region575 – 59420Interacts with HAX1 By similarity
Region787 – 80721Interacts with phospholamban 2 By similarity

Sites

Active site35114-aspartylphosphate intermediate By similarity
Metal binding3041Calcium 2; via carbonyl oxygen By similarity
Metal binding3051Calcium 2; via carbonyl oxygen By similarity
Metal binding3071Calcium 2; via carbonyl oxygen By similarity
Metal binding3091Calcium 2 By similarity
Metal binding7021Magnesium By similarity
Metal binding7061Magnesium By similarity
Metal binding7671Calcium 1 By similarity
Metal binding7701Calcium 1 By similarity
Metal binding7951Calcium 2 By similarity
Metal binding7981Calcium 1 By similarity
Metal binding7991Calcium 1 By similarity
Metal binding7991Calcium 2 By similarity
Metal binding9071Calcium 1 By similarity

Amino acid modifications

Modified residue2941Nitrated tyrosine By similarity
Modified residue2951Nitrated tyrosine By similarity
Modified residue5371Phosphothreonine Ref.6
Modified residue6631Phosphoserine Ref.7
Cross-link143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5

Natural variations

Alternative sequence995 – 104450GKECV…DMFWS → AILE in isoform SERCA2A.
VSP_000359

Sequences

Sequence LengthMass (Da)Tools
Isoform SERCA2B (ATP2A2B) [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 06A753982116C421

FASTA1,044114,858
        10         20         30         40         50         60 
MENAHTKTVE EVLGHFGVNE STGLSLEQVK KLKERWGSNE LPAEEGKTLL ELVIEQFEDL 

        70         80         90        100        110        120 
LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILVA NAIVGVWQER NAENAIEALK 

       130        140        150        160        170        180 
EYEPEMGKVY RQDRKSVQRI KAKDIVPGDI VEIAVGDKVP ADIRLTSIKS TTLRVDQSIL 

       190        200        210        220        230        240 
TGESVSVIKH TDPVPDPRAV NQDKKNMLFS GTNIAAGKAM GVVVATGVNT EIGKIRDEMV 

       250        260        270        280        290        300 
ATEQERTPLQ QKLDEFGEQL SKVISLICIA VWIINIGHFN DPVHGGSWIR GAIYYFKIAV 

       310        320        330        340        350        360 
ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ 

       370        380        390        400        410        420 
MSVCRMFILD KVEGDTCSLN EFSITGSTYA PIGEVQKDDK PVKCHQYDGL VELATICALC 

       430        440        450        460        470        480 
NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTELK GLSKIERANA CNSVIKQLMK 

       490        500        510        520        530        540 
KEFTLEFSRD RKSMSVYCTP NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTPGV 

       550        560        570        580        590        600 
KQKIMSVIRE WGSGSDTLRC LALATHDNPL KREEMHLEDS ANFIKYETNL TFVGCVGMLD 

       610        620        630        640        650        660 
PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK AFTGREFDEL 

       670        680        690        700        710        720 
SPSAQRDACL NARCFARVEP SHKSKIVEFL QSFDEITAMT GDGVNDAPAL KKSEIGIAMG 

       730        740        750        760        770        780 
SGTAVAKTAS EMVLADDNFS TIVAAVEEGR AIYNNMKQFI RYLISSNVGE VVCIFLTAAL 

       790        800        810        820        830        840 
GFPEALIPVQ LLWVNLVTDG LPATALGFNP PDLDIMNKPP RNPKEPLISG WLFFRYLAIG 

       850        860        870        880        890        900 
CYVGAATVGA AAWWFIAADG GPRVSFYQLS HFLQCKEDNP DFDGVDCAIF ESPYPMTMAL 

       910        920        930        940        950        960 
SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE PLPLIFQITP 

       970        980        990       1000       1010       1020 
LNLTQWLMVL KISLPVILMD ETLKFVARNY LEQPGKECVQ PATKSSCSLS ACTDGISWPF 

      1030       1040 
VLLIMPLVVW VYSTDTNFSD MFWS 

« Hide

Isoform SERCA2A (ATP2A2A) [UniParc].

Checksum: AB29BFE4D49653BB
Show »

FASTA998109,753

References

« Hide 'large scale' references
[1]"Structure and organization of the mouse Atp2a2 gene encoding the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) isoforms."
Ver Heyen M., Reed T.D., Blough R.E., Zilberman A.L., Loukianov E., Van Baelen K., Raeymaekers L., Periasamy M., Wutack F.
Mamm. Genome 11:159-163(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SERCA2A AND SERCA2B).
Strain: 129/SvJ.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SERCA2B).
Strain: C57BL/6.
Tissue: Brain.
[3]Lubec G., Kang S.U., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 604-611 AND 638-655, MASS SPECTROMETRY.
Strain: C57BL/6 and OF1.
Tissue: Brain and Hippocampus.
[4]"TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and is necessary for collagen type I synthesis."
Stefanovic B., Stefanovic L., Schnabl B., Bataller R., Brenner D.A.
Mol. Cell. Biol. 24:1758-1768(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAM2.
[5]"A proteomics approach to identify the ubiquitinated proteins in mouse heart."
Jeon H.B., Choi E.S., Yoon J.H., Hwang J.H., Chang J.W., Lee E.K., Choi H.W., Park Z.-Y., Yoo Y.J.
Biochem. Biophys. Res. Commun. 357:731-736(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-143, MASS SPECTROMETRY.
Tissue: Heart.
[6]"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry."
Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R.
J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-537, MASS SPECTROMETRY.
Tissue: Liver.
[7]"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations."
Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M.
Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663, MASS SPECTROMETRY.
Tissue: Brain cortex.
[8]"S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products."
Boyd J.H., Kan B., Roberts H., Wang Y., Walley K.R.
Circ. Res. 102:1239-1246(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH S100A8 AND S100A9.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ131821 mRNA. Translation: CAB72436.1.
AJ223584 mRNA. Translation: CAA11450.1.
AF029982 Genomic DNA. Translation: AAD01889.1.
AJ131870 Genomic DNA. Translation: CAB41017.1.
AJ131870 Genomic DNA. Translation: CAB41018.1.
BC054531 mRNA. Translation: AAH54531.1.
BC054748 mRNA. Translation: AAH54748.1.
IPIIPI00338964.
IPI00468900.
RefSeqNP_001103610.1. NM_001110140.3.
NP_033852.1. NM_009722.3.
UniGeneMm.227583.

3D structure databases

ProteinModelPortalO55143.
SMRO55143. Positions 1-992.
ModBaseSearch...

Protein-protein interaction databases

IntActO55143. 3 interactions.

PTM databases

PhosphoSiteO55143.

Proteomic databases

PaxDbO55143.
PRIDEO55143.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031423; ENSMUSP00000031423; ENSMUSG00000029467.
ENSMUST00000177974; ENSMUSP00000136104; ENSMUSG00000029467.
GeneID11938.
KEGGmmu:11938.
UCSCuc008zli.2. mouse.

Organism-specific databases

CTD488.
MGIMGI:88110. Atp2a2.

Phylogenomic databases

eggNOGCOG0474.
GeneTreeENSGT00560000076887.
HOGENOMHOG000265621.
HOVERGENHBG105648.
InParanoidO55143.
KOK05853.
OMAWFVAAED.
OrthoDBEOG4SXNBQ.

Gene expression databases

ArrayExpressO55143.
BgeeO55143.
GenevestigatorO55143.
GermOnlineENSMUSG00000029467. Mus musculus.

Family and domain databases

Gene3D1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProIPR005782. ATPase_P-typ_Ca-transp_IIA.
IPR006068. 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.
IPR001757. Cation_transp_P_typ_ATPase.
IPR023214. HAD-like_dom.
[Graphical view]
PANTHERPTHR24093. PTHR24093. 1 hit.
PfamPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF00702. Hydrolase. 1 hit.
[Graphical view]
PRINTSPR00119. CATATPASE.
PR00120. HATPASE.
SMARTSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMSSF81660. ATPase_cation_domN. 1 hit.
SSF56784. HAD-like_dom. 1 hit.
TIGRFAMsTIGR01116. ATPase-IIA1_Ca. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATP2A2. mouse.
NextBio280039.
SOURCESearch...

Entry information

Entry nameAT2A2_MOUSE
AccessionPrimary (citable) accession number: O55143
Secondary accession number(s): Q9R2A9, Q9WUT5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families