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FLASH GENE
Symbol ATP2A1 contributors: mct - updated : 17-04-2014
HGNC name ATPase, Ca++ transporting, cardiac muscle, fast twitch 1
HGNC id 811
Corresponding disease
BROD Brody myopathy
Location 16p11.2      Physical location : 28.889.808 - 28.915.830
Synonym name
  • skeletal muscle sarco(endo)-plasmic reticulum calcium ATPase
  • calcium pump 1
  • endoplasmic reticulum class 1/2 Ca
  • sarcoplasmic reticulum Ca2+-ATPase
  • Synonym symbol(s) ATP2A, SERCA1
    EC.number 3.6.3.8
    DNA
    TYPE functioning gene
    STRUCTURE 26.02 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure
  • MBNL1-binding sites in intron 22 (second and third MBNL1-binding motifs are necessary for MBNL1-dependent inclusion of exon 22 )
  • MAPPING cloned Y linked N status confirmed
    Physical map
    LOC390687 16 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC388228 16 similar to SH3-binding kinase LOC388229 16 similar to Group X secretory phospholipase A2 precursor (Phosphatidylcholine 2-acylhydrolase GX) (GX sPLA2) (sPLA2-X) EIF3S8 16p11.2 eukaryotic translation initiation factor 3, subunit 8, 110kDa LOC283890 16p12.1 similar to nuclear pore complex interacting protein LOC388230 16 similar to MGC9515 protein LOC388231 16 LOC388231 SULT1A1 16p12.1 sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1 SULT1A2 16p12-p11.2 sulfotransferase family, cytosolic, 1A, phenol-preferring, member 2 LOC112869 16p12.1 hypothetical protein BC011981 P8 16p11.2 p8 protein (candidate of metastasis 1) IL27  interleukin 27 LOC388232 16 similar to apolipoprotein B48 receptor CLN3 16p12.1-p11.2 ceroid-lipofuscinosis, neuronal 3, juvenile (Batten, Spielmeyer-Vogt disease) LOC388233 16 similar to MGC9515 protein APOB48R 16p11 apolipoprotein B48 receptor LOC388234 16 similar to nuclear pore complex interacting protein LOC390688 16 similar to CDC37-like gene LOC388235 16 LOC388235 LOC388236 16 similar to MGC9515 protein A2LP 16p11 ataxin 2 related protein TUFM 16p11.2 Tu translation elongation factor, mitochondrial SH2B 16p12.1 Tu translation elongation factor, mitochondrial ATP2A1 16p12.1 ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 FRA 16p12.1 Fos-related antigen CD19 16p11.2 CD19 antigen FLJ14639 16p12.1 hypothetical protein FLJ14639 SPINL 16p12.1 spinster-like LAT 16p11.2 linker for activation of T cells LOC388237 16 similar to nuclear pore complex interacting protein LOC388238 16 similar to RRN3 LOC283892 16p12.1 hypothetical gene supported by NM_017869; AK023827 LOC283895 16p12.1 hypothetical LOC283895 LOC388239 16 similar to nuclear pore complex interacting protein LOC388240 16 similar to MGC9515 protein LOC388241 16 similar to PI-3-kinase-related kinase SMG-1 isoform 2; lambda/iota protein kinase C-interacting protein; phosphatidylinositol 3-kinase-related protein kinase MGC5178 16p12.1 hypothetical protein MGC5178 LOC388242 16 similar to hypothetical protein BC011981 KIAA0220 16p12.1 KIAA0220 protein LAT1-3TM 16p12 LAT1-3TM protein
    RNA
    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 2007 1772832
  • variant b or SERCA1 a
  • longer transcript but shorter isoform
  • adult form
  • contains exon 22
  • 22 - 3528 110 1001 . neonatal fast twitch muscle . expressed in fetal/neonatal stages but is completely replaced by SERCA1a in adult muscle fiber 2007 1772832
  • variant a or SERCA1 b
  • lacking an exon in the 3' coding region, resulting in a frameshift and use of a downstream termination codon compared to variant a
  • 21 splicing 3219 - 859 - 2007 1772832
  • 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 2008 19061639
  • 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
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth    
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period neonatal
    Text transciently, in a minor form SERCA1B in neonatal fibers
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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)
  • HOMOLOGY
    interspecies ortholog to murine Atp2a1
    Homologene
    FAMILY
  • cation transport ATPase (P-type) family
  • type IIA subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component ATP2A1/ PLN complex regulates Ca2+ translocation into the sarcoplasmic reticulum (SR) of cardiomyocytes and constitutes the main mechanism of cardiac relaxation (diastole)
    INTERACTION
    DNA
    RNA
    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
  • allosteric regulation of ATP2A1 depends on the conformational equilibrium of PLN
  • cell & other
    REGULATION
    induced by decreased contractile activity
    inhibited by PLN at low calcium concentration
    repressed by increased contractile activity
    ASSOCIATED DISORDERS
    corresponding disease(s) BROD
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathy 
    novel therapeutic approach using ATP2A1 to abrogate the altered intracellular Ca(2+) levels that underlie most forms of Muscular dystrophies (MDs)
    ANIMAL & CELL MODELS
  • 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)