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Protein

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Gene

ATP2A2

Organism
Sus scrofa (Pig)
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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi304 – 3041Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi305 – 3051Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi307 – 3071Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi309 – 3091Calcium 2By similarity
Active sitei351 – 35114-aspartylphosphate intermediateBy similarity
Metal bindingi702 – 7021MagnesiumBy similarity
Metal bindingi706 – 7061MagnesiumBy similarity
Metal bindingi767 – 7671Calcium 1By similarity
Metal bindingi770 – 7701Calcium 1By similarity
Metal bindingi795 – 7951Calcium 2By similarity
Metal bindingi798 – 7981Calcium 1By similarity
Metal bindingi799 – 7991Calcium 1By similarity
Metal bindingi799 – 7991Calcium 2By similarity
Metal bindingi907 – 9071Calcium 1By similarity

GO - Molecular functioni

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

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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4848CytoplasmicBy similarityAdd
BLAST
Transmembranei49 – 6921Helical; Name=1By similarityAdd
BLAST
Topological domaini70 – 8920LumenalBy similarityAdd
BLAST
Transmembranei90 – 11021Helical; Name=2By similarityAdd
BLAST
Topological domaini111 – 253143CytoplasmicBy similarityAdd
BLAST
Transmembranei254 – 27320Helical; Name=3By similarityAdd
BLAST
Topological domaini274 – 29522LumenalBy similarityAdd
BLAST
Transmembranei296 – 31318Helical; Name=4By similarityAdd
BLAST
Topological domaini314 – 756443CytoplasmicBy similarityAdd
BLAST
Transmembranei757 – 77620Helical; Name=5By similarityAdd
BLAST
Topological domaini777 – 78610LumenalBy similarity
Transmembranei787 – 80721Helical; Name=6By similarityAdd
BLAST
Topological domaini808 – 82720CytoplasmicBy similarityAdd
BLAST
Transmembranei828 – 85023Helical; Name=7By similarityAdd
BLAST
Topological domaini851 – 89646LumenalBy similarityAdd
BLAST
Transmembranei897 – 91620Helical; Name=8By similarityAdd
BLAST
Topological domaini917 – 92913CytoplasmicBy similarityAdd
BLAST
Transmembranei930 – 94819Helical; Name=9By similarityAdd
BLAST
Topological domaini949 – 96315LumenalBy similarityAdd
BLAST
Transmembranei964 – 98421Helical; Name=10By similarityAdd
BLAST
Topological domaini985 – 104258CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Sarcoplasmic reticulum

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10421042Sarcoplasmic/endoplasmic reticulum calcium ATPase 2PRO_0000046198Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei38 – 381PhosphoserineBy similarity
Cross-linki143 – 143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei294 – 2941Nitrated tyrosineBy similarity
Modified residuei295 – 2951Nitrated tyrosineBy similarity
Modified residuei441 – 4411PhosphothreonineBy similarity
Modified residuei531 – 5311PhosphoserineBy similarity
Modified residuei580 – 5801PhosphoserineBy similarity
Modified residuei663 – 6631PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Nitration, Phosphoprotein, Ubl conjugation

Proteomic databases

PeptideAtlasiP11607.
PRIDEiP11607.

Expressioni

Tissue specificityi

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

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
CANXP278242EBI-8004986,EBI-355947From a different organism.
OPRD1P411432EBI-8004986,EBI-2624456From a different organism.

Protein-protein interaction databases

IntActiP11607. 2 interactions.
MINTiMINT-7889308.

Structurei

3D structure databases

ProteinModelPortaliP11607.
SMRiP11607. Positions 1-992.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni370 – 40031Interacts with phospholamban 1By similarityAdd
BLAST
Regioni575 – 59420Interacts with HAX1By similarityAdd
BLAST
Regioni787 – 80721Interacts with phospholamban 2By similarityAdd
BLAST
Regioni788 – 1042255Interaction with TMEM64 and PDIA3By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG105648.
InParanoidiP11607.
KOiK05853.

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: P11607-1) [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 PIGEVHKDDK
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 LALATHDNPM RREEMNLEDS ANFIKYETNL TFVGCVGMLD
610 620 630 640 650
PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK
660 670 680 690 700
AFTGREFDEL NPSAQREACL 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 GPRVTFYQLS HFLQCKEDNP DFEGVDCAVF ESPYPMTMAL
910 920 930 940 950
SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE
960 970 980 990 1000
PLPLIFQITP LNLTQWLMVL KISLPVILMD ETLKFVARNY LEPGKECVQP
1010 1020 1030 1040
ATKSCSFSAC TDGISWPFVL LIMPLVIWVY STDTNFSDMF WS
Length:1,042
Mass (Da):114,792
Last modified:October 1, 1989 - v1
Checksum:iA68EC9E41494D532
GO
Isoform 2 (identifier: P11607-2) [UniParc]FASTAAdd to basket

Also known as: ATP2A2A, SERCA2a

The sequence of this isoform differs from the canonical sequence as follows:
     994-1042: GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS → AILE

Show »
Length:997
Mass (Da):109,726
Checksum:i66697619E312CA3E
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei994 – 104249GKECV…DMFWS → AILE in isoform 2. 1 PublicationVSP_000360Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X15074 mRNA. Translation: CAA33170.1.
X15073 mRNA. Translation: CAA33169.1.
X53754 Genomic DNA. Translation: CAA37783.1.
X53754 Genomic DNA. Translation: CAA37784.1.
PIRiS04651.
S04652.
RefSeqiNP_999030.1. NM_213865.1. [P11607-1]
UniGeneiSsc.97090.

Genome annotation databases

GeneIDi396875.
KEGGissc:396875.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X15074 mRNA. Translation: CAA33170.1.
X15073 mRNA. Translation: CAA33169.1.
X53754 Genomic DNA. Translation: CAA37783.1.
X53754 Genomic DNA. Translation: CAA37784.1.
PIRiS04651.
S04652.
RefSeqiNP_999030.1. NM_213865.1. [P11607-1]
UniGeneiSsc.97090.

3D structure databases

ProteinModelPortaliP11607.
SMRiP11607. Positions 1-992.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP11607. 2 interactions.
MINTiMINT-7889308.

Proteomic databases

PeptideAtlasiP11607.
PRIDEiP11607.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi396875.
KEGGissc:396875.

Organism-specific databases

CTDi488.

Phylogenomic databases

HOVERGENiHBG105648.
InParanoidiP11607.
KOiK05853.

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...

Publicationsi

  1. "Evidence for two isoforms of the endoplasmic-reticulum Ca2+ pump in pig smooth muscle."
    Eggermont J.A., Wuytack F., de Jaegere S., Nelles L., Casteels R.
    Biochem. J. 260:757-761(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Tissue: Stomach smooth muscle.
  2. "Characterization of the 3' end of the pig sarcoplasmic/endoplasmic-reticulum Ca2+ pump gene 2."
    Eggermont J.A., Wuytack F., Casteels R.
    Biochim. Biophys. Acta 1088:448-451(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 842-1042 (ISOFORMS 1 AND 2).
  3. "Characterization of the mRNAs encoding the gene 2 sarcoplasmic/endoplasmic-reticulum Ca2+ pump in pig smooth muscle."
    Eggermont J.A., Wuytack F., Casteels R.
    Biochem. J. 266:901-907(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ALTERNATIVE SPLICING.

Entry informationi

Entry nameiAT2A2_PIG
AccessioniPrimary (citable) accession number: P11607
Secondary accession number(s): P11606, P79426, P79427
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: July 6, 2016
This is version 142 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.