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Symbol ATP2A1 contributors: mct - updated : 23-10-2017
HGNC name ATPase, Ca++ transporting, cardiac muscle, fast twitch 1
HGNC id 811
TRANSCRIPTS type messenger
text splicing regulation of ATP2A1 is well known to play important roles in muscle development and maturation
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
23 - 3570 109 994 adult fast- twitch muscle 2015 25487304
  • variant b or SERCA1 a
  • longer transcript but shorter isoform
  • adult form
  • contains exon 22
  • has C-terminal glycine while SERCA1b has an octapeptide tail instead
  • 22 - 3528 110 1001 . neonatal fast twitch muscle . expressed in fetal/neonatal stages but is completely replaced by SERCA1a in adult muscle fiber 2015 25487304
  • SERCA1 b
  • lacking an exon in the 3' coding region, resulting in a frameshift and use of a downstream termination codon compared to SERCA1 a
  • SERCA1a has C-terminal glycine while SERCA1b has an octapeptide tail instead
  • is associated with DM2
  • 21 splicing 3219 - 859 - 2015 25487304
  • excluded exon 22, in skeletal muscle of DM1 patients
  • sequestration of MBNL1 into the CUG repeat expansion of DMPK mRNA could cause the exclusion of ATP2A1 exon 22, and the expression of this aberrant splicing form could affect the regulation of Ca(2+) concentration of sarcoplasmic reticulum in DM1 patients
  • - - - - - localized in the ER-mitochondria microdomains 2015 25487304
  • truncated variant
  • determines ER Ca(2+) depletion due to increased Ca(2+) leak, an increased number of ER-mitochondria contact sites, and inhibition of mitochondria movements
  • by bridging ER stress to apoptosis through increased ER-mitochondria Ca(2+) transfer, S1T acts as an essential determinant of cellular fate
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    at STAGE
    physiological period neonatal
    Text transciently, in a minor form SERCA1B in neonatal fibers
  • ten transmembrane coiled coil helices (four of which containing Ca2+ binding sites)
  • a cytoplasmic beta strand between TM2/3
  • a phosphorylation and ATP binding globular domains, between TM4/5
  • five YGCU(U/G)Y motifs that could potentially serve as MBNL1-binding motifs, in intron 22 (the second and third sites were important for regulation of exon 22 splicing)
    interspecies ortholog to murine Atp2a1
  • cation transport ATPase (P-type) family
  • type IIA subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text sarco/endoplasmic reticulum
    basic FUNCTION
  • intracellular pum catalyzing the hydrolysis of ATP couple with the translocation of Ca2+ from the cytosol to the sarcoplasmic reticulum lumen
  • is essential for muscle function by transporting Ca(2+) from the cytosol into the sarcoplasmic reticulum through ATP hydrolysis
  • in the cardiac muscle, SERCA hydrolyzes one ATP molecule to translocate two Ca(2+) ions into the SR membrane per enzymatic cycle
  • PKC signaling is involved in the splicing of ATP2A1 and provide new evidence for a link between alternative splicing and PKC signaling
  • re-sequestration of Ca(2+) into the sarcoplasmic reticulum is catalysed by ATP2A1, which has a key role in defining the contractile properties of skeletal and heart muscle tissue
  • ATP2A1 function is controlled by PLN conformational equilibrium and phosphorylation promotes the B state via a conformational shift mechanism
  • involved in muscular contraction and excitation
  • its function depends on the equilibria between transient conformational states of PLN
  • sarco(endo)plasmic reticulum Ca2+-ATPase of skeletal muscle, that is essential for muscle relaxation and maintenance of low resting Ca2+ levels in the myoplasm
    a component ATP2A1/ PLN complex regulates Ca2+ translocation into the sarcoplasmic reticulum (SR) of cardiomyocytes and constitutes the main mechanism of cardiac relaxation (diastole)
    small molecule metal binding, cofactor, nucleotide,
  • ATP binding
  • Ca2+ binding
  • Mg2+ dependent
  • protein
  • associated with SLN and PLN
  • unphosphorylated PLN reduces ATP2A1 affinity for Ca(2+) and affects the enzymatic turnover
  • HSPA1A interacts with ATP2A1 to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with HSPA1A upregulation
  • TRIM72 binds to sarcoplasmic reticulum Ca(2+)-ATPase 1a (ATP2A1) via its tripartite motif (TRIM) and PRY domains
  • allosteric regulation of ATP2A1 depends on the conformational equilibrium of PLN
  • EBF3 binds directly to the promoter of ATP2A1 and synergises with MYOD1 in the induction of ATP2A1
  • SLN and PLN inhibit ATP2A1 by using a similar mechanism
  • ANK1 interacts with ATP2A1 through its TM and cytoplasmic domains to regulate ATP2A1 activity and modulate sequestration of Ca(2+) in the sarcoplasmic reticulum lumen
  • ANK1 interacts likely with SLN both directly and in complex with ATP2A1 and reduces SLN inhibitory effect on ATP2A1 activity
  • role for TNFRSF11A as a key regulator of Ca(2+)storage and ATP2A1 activity, ultimately affecting denervated skeletal muscle function
  • cell & other
    induced by decreased contractile activity
    inhibited by PLN at low calcium concentration
    repressed by increased contractile activity
    Other sphingolipid could control the activity of the ATP2A1, and hence sphingosine may participate in the regulation of [Ca(2+)]I in mammalian cells
    corresponding disease(s) BROD
    Variant & Polymorphism
    Candidate gene
    Therapy target
    novel therapeutic approach using ATP2A1 to abrogate the altered intracellular Ca(2+) levels that underlie most forms of Muscular dystrophies (MDs)
  • ATP2A1 null mice have progressive cyanosis and gasping respiration and succumb from respiratory failure shortly after birth
  • a missense mutation in the ATP2A1 gene in congenital pseudomyotonia of Chianina cattle (the electromyographic examination does not show any alteration, not even during the phase of the muscle contraction) (Drögemüller 2008)