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Protein

Sarcoplasmic/endoplasmic reticulum calcium ATPase 1

Gene

ATP2A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

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

Enzyme 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 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 bindingi703MagnesiumBy similarity1
Metal bindingi707MagnesiumBy similarity1
Metal bindingi768Calcium 1By similarity1
Metal bindingi771Calcium 1By similarity1
Metal bindingi796Calcium 2By similarity1
Metal bindingi799Calcium 1By similarity1
Metal bindingi800Calcium 1By similarity1
Metal bindingi800Calcium 2By similarity1
Metal bindingi908Calcium 1By similarity1

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • calcium-transporting ATPase activity Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • apoptotic mitochondrial changes Source: BHF-UCL
  • calcium ion import Source: BHF-UCL
  • calcium ion transport Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: BHF-UCL
  • ion transmembrane transport Source: Reactome
  • maintenance of mitochondrion location Source: BHF-UCL
  • negative regulation of endoplasmic reticulum calcium ion concentration Source: BHF-UCL
  • negative regulation of striated muscle contraction Source: UniProtKB
  • positive regulation of endoplasmic reticulum calcium ion concentration Source: BHF-UCL
  • positive regulation of fast-twitch skeletal muscle fiber contraction Source: UniProtKB
  • positive regulation of mitochondrial calcium ion concentration Source: BHF-UCL
  • regulation of cardiac conduction Source: Reactome
  • regulation of striated muscle contraction Source: UniProtKB
  • relaxation of skeletal muscle Source: BHF-UCL
  • response to endoplasmic reticulum stress Source: BHF-UCL

Keywordsi

Molecular functionHydrolase
Biological processCalcium transport, Ion transport, Transport
LigandATP-binding, Calcium, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1912420 Pre-NOTCH Processing in Golgi
R-HSA-418359 Reduction of cytosolic Ca++ levels
R-HSA-5578775 Ion homeostasis
R-HSA-936837 Ion transport by P-type ATPases
SIGNORiO14983

Names & Taxonomyi

Protein namesi
Recommended name:
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (EC:3.6.3.8)
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000196296.13
HGNCiHGNC:811 ATP2A1
MIMi108730 gene
neXtProtiNX_O14983

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 – 757CytoplasmicBy similarityAdd BLAST444
Transmembranei758 – 777Helical; Name=5By similarityAdd BLAST20
Topological domaini778 – 787LumenalBy similarity10
Transmembranei788 – 808Helical; Name=6By similarityAdd BLAST21
Topological domaini809 – 828CytoplasmicBy similarityAdd BLAST20
Transmembranei829 – 851Helical; Name=7By similarityAdd BLAST23
Topological domaini852 – 897LumenalBy similarityAdd BLAST46
Transmembranei898 – 917Helical; Name=8By similarityAdd BLAST20
Topological domaini918 – 930CytoplasmicBy similarityAdd BLAST13
Transmembranei931 – 949Helical; Name=9By similarityAdd BLAST19
Topological domaini950 – 964LumenalBy similarityAdd BLAST15
Transmembranei965 – 985Helical; Name=10By similarityAdd BLAST21
Topological domaini986 – 1001CytoplasmicBy similarityAdd BLAST16

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Brody myopathy (BRM)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of muscle function that is characterized by painless muscle cramping and exercise-induced impairment of muscle relaxation.
See also OMIM:601003
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015588789P → L in BRM; almost complete loss of Ca(2+) transport activity because of reduced Ca(2+) affinity. 1 PublicationCorresponds to variant dbSNP:rs121918115Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi487
MalaCardsiATP2A1
MIMi601003 phenotype
OpenTargetsiENSG00000196296
Orphaneti53347 Brody myopathy
PharmGKBiPA25105

Chemistry databases

ChEMBLiCHEMBL3136
DrugBankiDB04444 Tetrafluoroaluminate Ion
GuidetoPHARMACOLOGYi840

Polymorphism and mutation databases

BioMutaiATP2A1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000461871 – 1001Sarcoplasmic/endoplasmic reticulum calcium ATPase 1Add BLAST1001

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei441PhosphothreonineBy similarity1
Modified residuei569PhosphothreonineBy similarity1
Modified residuei581PhosphoserineBy similarity1
Disulfide bondi876 ↔ 8881 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiO14983
MaxQBiO14983
PaxDbiO14983
PeptideAtlasiO14983
PRIDEiO14983

PTM databases

iPTMnetiO14983
PhosphoSitePlusiO14983
SwissPalmiO14983

Expressioni

Tissue specificityi

Skeletal muscle, fast twitch muscle (type II) fibers.1 Publication

Developmental stagei

Isoform SERCA1A accounts for more than 99% of SERCA1 isoforms expressed in adult skeletal muscle, while isoform SERCA1B predominates in neo-natal skeletal muscle.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

Gene expression databases

BgeeiENSG00000196296
CleanExiHS_ATP2A1
ExpressionAtlasiO14983 baseline and differential
GenevisibleiO14983 HS

Organism-specific databases

HPAiCAB002310
CAB032706

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 similarity

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi106977, 24 interactors
CORUMiO14983
IntActiO14983, 6 interactors
MINTiO14983
STRINGi9606.ENSP00000349595

Chemistry databases

BindingDBiO14983

Structurei

3D structure databases

ProteinModelPortaliO14983
SMRiO14983
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni370 – 400Interaction with phospholamban 1By similarityAdd BLAST31
Regioni788 – 808Interaction with phospholamban 2By similarityAdd BLAST21

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0202 Eukaryota
COG0474 LUCA
GeneTreeiENSGT00890000139334
HOGENOMiHOG000265621
HOVERGENiHBG105648
InParanoidiO14983
KOiK05853
OMAiTTRVPMT
OrthoDBiEOG091G01LE
PhylomeDBiO14983
TreeFamiTF300651

Family and domain databases

Gene3Di3.40.1110.10, 1 hit
3.40.50.1000, 2 hits
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
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, 3 hits
TIGRFAMsiTIGR01116 ATPase-IIA1_Ca, 1 hit
TIGR01494 ATPase_P-type, 2 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform SERCA1B (identifier: O14983-1) [UniParc]FASTAAdd to basket
Also known as: ATP2A1B, Neonatal

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
MEAAHAKTTE ECLAYFGVSE TTGLTPDQVK RNLEKYGLNE LPAEEGKTLW
60 70 80 90 100
ELVIEQFEDL LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA
110 120 130 140 150
NAIVGVWQER NAENAIEALK EYEPEMGKVY RADRKSVQRI KARDIVPGDI
160 170 180 190 200
VEVAVGDKVP ADIRILAIKS TTLRVDQSIL TGESVSVIKH TEPVPDPRAV
210 220 230 240 250
NQDKKNMLFS GTNIAAGKAL GIVATTGVGT 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 KVDGDICLLN EFSITGSTYA PEGEVLKNDK
410 420 430 440 450
PVRPGQYDGL VELATICALC NDSSLDFNEA KGVYEKVGEA TETALTTLVE
460 470 480 490 500
KMNVFNTDVR SLSKVERANA CNSVIRQLMK KEFTLEFSRD RKSMSVYCSP
510 520 530 540 550
AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPLTGP VKEKIMAVIK
560 570 580 590 600
EWGTGRDTLR CLALATRDTP PKREEMVLDD SARFLEYETD LTFVGVVGML
610 620 630 640 650
DPPRKEVTGS IQLCRDAGIR VIMITGDNKG TAIAICRRIG IFGENEEVAD
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 DGPHVNYSQL THFMQCTEDN THFEGIDCEV FEAPEPMTMA
910 920 930 940 950
LSVLVTIEMC NALNSLSENQ SLLRMPPWVN IWLLGSICLS MSLHFLILYV
960 970 980 990 1000
DPLPMIFKLR ALDLTQWLMV LKISLPVIGL DEILKFVARN YLEDPEDERR

K
Length:1,001
Mass (Da):110,252
Last modified:January 1, 1998 - v1
Checksum:iC8F33809B56FDDEE
GO
Isoform SERCA1A (identifier: O14983-2) [UniParc]FASTAAdd to basket
Also known as: ATP2A1A, Adult

The sequence of this isoform differs from the canonical sequence as follows:
     994-1001: DPEDERRK → G

Show »
Length:994
Mass (Da):109,283
Checksum:i3C07972DB585C083
GO
Isoform 3 (identifier: O14983-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-125: Missing.
     994-1001: DPEDERRK → G

Note: No experimental confirmation available.
Show »
Length:869
Mass (Da):95,199
Checksum:iA1D5541B75BA3014
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015588789P → L in BRM; almost complete loss of Ca(2+) transport activity because of reduced Ca(2+) affinity. 1 PublicationCorresponds to variant dbSNP:rs121918115Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0547701 – 125Missing in isoform 3. 1 PublicationAdd BLAST125
Alternative sequenceiVSP_000355994 – 1001DPEDERRK → G in isoform SERCA1A and isoform 3. 2 Publications8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96781
, U96773, U96774, U96775, U96776, U96777, U96778, U96779, U96780 Genomic DNA Translation: AAB53113.1
U96781
, U96773, U96774, U96775, U96776, U96777, U96778, U96779, U96780 Genomic DNA Translation: AAB53112.1
AK128456 mRNA Translation: BAG54679.1
AK291314 mRNA Translation: BAF84003.1
AC109460 Genomic DNA No translation available.
AC133550 Genomic DNA No translation available.
CCDSiCCDS10643.1 [O14983-1]
CCDS42139.1 [O14983-2]
CCDS66997.1 [O14983-3]
RefSeqiNP_001273004.1, NM_001286075.1 [O14983-3]
NP_004311.1, NM_004320.4 [O14983-2]
NP_775293.1, NM_173201.3 [O14983-1]
UniGeneiHs.657344

Genome annotation databases

EnsembliENST00000357084; ENSP00000349595; ENSG00000196296 [O14983-1]
ENST00000395503; ENSP00000378879; ENSG00000196296 [O14983-2]
ENST00000536376; ENSP00000443101; ENSG00000196296 [O14983-3]
GeneIDi487
KEGGihsa:487
UCSCiuc002drn.1 human [O14983-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAT2A1_HUMAN
AccessioniPrimary (citable) accession number: O14983
Secondary accession number(s): A8K5J9, B3KY17, O14984
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: March 28, 2018
This is version 183 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health