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FLASH GENE
Symbol ATP2A2 contributors: mct - updated : 22-11-2017
HGNC name ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
HGNC id 812
Corresponding disease
AKV acrokeratosis verruciformis
DAR Darier-White disease
Location 12q24.11      Physical location : 110.719.031 - 110.788.895
Synonym name
  • sarcoplasmic endoplasmic reticulum calcium ATPase2
  • Ca2+ transporting sarco/endo-plasmic reticulum pump type 2 isoforms
  • endoplasmic reticulum class 1/2 Ca
  • calcium pump 2
  • cardiac Ca2+ ATPase
  • calcium-transporting ATPase sarcoplasmic reticulum type,
  • slow twitch skeletal muscle isoform
    Synonym symbol(s) ATP2B, SERCA2, ATA2, DD, MGC45367, ATP2B, FLJ20293, FLJ38063, DKFZp686P0211
    EC.number 3.6.3.8
    DNA
    TYPE functioning gene
    STRUCTURE 69.87 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure Sp1 binding site positively transactivates the ATP2A2 promoter in Keratinocytes
    MAPPING cloned Y linked N status confirmed
    Map cen - D12S1110 - (D12S1865 - D12S353 - D12S1126 ) - D12S1163E - D12S1127 - D12S84 - D12S1893 - SELPLG - D12S1637 - (D12S1876 - D12S1605 ) - D12S1440 - DAO - D12S105 - D12S1204E - D12S1583 - D12S1645 - D12S1111 - D12S1339 - D12S1324 - D12S1327 - D12S1838 - (D12S2308 ,D12S1332 ) - SCA2 - D12S2307 - D12S2303 - D12S2298 - ALDH2 - (D12S1344 ,D12S1333 ) - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 4359 - 997 . heart, skeletal muscle, slow twitch and cardiac muscle . restricted to a region within 1.5 microm of the nucleus in pulmonary arterial smooth muscle cells (PMID: 20177054) 2009 19541629
    also called ATP2A2a (HK2), or SERCA2a
    20 splicing 8329 - 1042 . ubiquitously : the most abundant isoform in smooth muscle, non muscle tissue, skin (epidermis), liver . primarily found within 1.5 microm of the plasma membrane in pulmonary arterial smooth muscle cells (PMID: 20177054) 2009 19541629
  • also called SERCA2b
  • alternative splicing of exon 20
  • four C terminal residues replaced by a sequence of 49aa
  • mutated in Darier disease
  • playing a key role in the biology of the epidermis
  • coexpressed with the related SERCA type 3 (SERCA3) in many tissues
  • maintains high Ca(2+) concentration in the lumen of the endoplasmic reticulum, interacts specifically with the human delta opioid receptor during early steps of receptor biogenesis in human embryonic kidney 293 cells (PMID: 17588601)
  • association with SERCA2b is required for efficient folding and/or membrane integration of G protein-coupled receptors (PMID: 17588601)
  • high apparent Ca2+ affinity resulting from a direct interaction between its unique C terminus and upstream luminal loops (PMID: 19846779)
  • 19 - 8248 - 1015 . premature monocytes . only detected in a confined area of cardiomyocytes, in close proximity to the sarcolemma 2006 16402920
  • also called SERCA2C
  • having lower apparent affinity for cytosolic Ca2+ than SERCA2A and a catalytic turnover rate similar to SERCA2B
  • - - - - 980 skeletal muscle 2005 15972723
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver   highly Homo sapiens
    Nervousbrain    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis  
    Muscularsmooth  highly
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatozoa Homo sapiens
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion sperm
    at STAGE
    physiological period embryo
    Text developing heart (8-wk gestation)
    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 (the latter linked to stalk sector 5) between TM4/5
  • HOMOLOGY
    interspecies homolog to murine Atp2a2
    Homologene
    FAMILY
  • cation transport ATPase (P-type) family
  • type IIA subfamily
  • CATEGORY enzyme , signaling , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nuclear envelope
    text
  • sarco/endoplasmic membrane X nuclear envelope ATP2A2-b
  • sarcoplasmic reticulum (SERCA2A)
  • basic FUNCTION
  • membrane protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to the Sarcoplasmic reticulum
  • sarco/endoplasmic reticulum Ca2+ pump
  • playing a pivotal role in intracellular Ca2+ signaling and in the regulation of contraction/relaxation cycle
  • rate determining factor of Ca2+ reuptake into the SR
  • playing an important role in epidermal cell adhesion and differentiation
  • playing a role in sperm
  • with ATP2A3, modulate thrombin-stimulated SOCE (store-operated Ca(2+)entry) probably by direct interaction with the TRPC1 channel inplatelets
  • contributes to cellular calcium homeostasis
  • low Ca2+-affinity ATP2A3, and the high Ca2+-affinity ATP2A2 enzymes are simultaneously expressed in B cells
  • SERCA2B delivers Ca2+ to sarcoplasmic reticulum Ca2+ stores, where Ca2+ is then released via RYR1 to mediate vasodilatation in pulmonary arterial smooth muscle
  • SERCA2A delivers Ca2+ to sarcoplasmic reticulum Ca2+ stores, where Ca2+ is then released via RYR3 and RYR2 to initiate vasoconstriction in pulmonary arterial smooth muscle
  • Ca2+-transport ATPase, whose only known function is the reuptake of Ca2+ from the cytosol into the ER lumen (
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS locomotion , active transport
    text calcium transporter, slow-twitch muscle
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • interacting with CALR (degraded via a proteasome-dependent pathway following the formation of a complex with CALR under the stress with H(2)O(2))
  • interacting with PLN (a weak inhibitor of ATP2A2a, PLN(R9C), which is diminished in its ability to modify the level of ATP2A2a activity, leads to heart failure despite fast sarcoplasmic reticulum Ca(2+) reuptake)
  • although TFAM and TFB2M are recognized as mtDNA-specific transcription factors, they also regulate transcription of nuclear DNA, ATP2A2 gene
  • binds to SUMO1 and to ubiquitin-conjugating enzyme E2I (UBE2I)
  • interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia
  • AGTRAP enhances the activity of ATP2A2 and, consequently, facilitates ventricular relaxation
  • cell & other
    REGULATION
    inhibited by by phospholamban (PLN) and sarcolipin (SLN)
    Other SUMOylated at lysines 480 and 585 and this SUMOylation is essential for preserving its ATPase activity and stability
    SUMOylation increases the stability of ATP2A2 by preventing 26S-proteasomal degradation of ATP2A2
    ASSOCIATED DISORDERS
    corresponding disease(s) DAR , AKV
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in acantholytic dyskeratotic naevus
    constitutional     --low  
    in airway smooth muscle in asthma that contributes to its secretory and hyperproliferative phenotype and which may play a key role in mechanisms of airway remodeling
    constitutional     --low  
    loss of SERCA2b function/regulation and a consequent decrease in ER calcium levels in the liver reduce chaperone function and ER folding capacity (
    constitutional     --low  
    of SUMOylated ATP2A2 was significantly reduced in failing hearts compared to normal heart
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    development of therapeutic agents targeted at effectively enhancing SERCA2b activity, which would in turn decrease ER stress, enhance glucose tolerance, and reduce hepatosteatosis
    ANIMAL & CELL MODELS
  • overexpression of Serca2b in the liver of obese mice significantly reduces the lipogenic gene expression and the triglyceride content in the liver