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FLASH GENE
Symbol ATP2B2 contributors: npt/mct/pgu - updated : 15-11-2016
HGNC name ATPase, Ca++ transporting, plasma membrane 2
HGNC id 815
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumearinnercochlea   Homo sapiens
 earinner    Homo sapiens
Nervousbrainhindbraincerebellum highly Homo sapiens
 brainlimbic systemhippocampus   Homo sapiens
Reproductivefemale systembreastmammary gland moderately Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
NervousPurkinje cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period perinatal
Text in lactating mammary gland
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 10 transmembrane domains
  • two large intracellular loops
  • and N- and C-terminal cytoplasmic tails
  • HOMOLOGY
    Homologene
    FAMILY
  • cation transport ATPase (p-type) family
  • type IIb subfamily
  • CATEGORY enzyme , transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    basic FUNCTION
  • ATPase, Ca++ transporting, B2 plasma membrane, mediating the extrusion of CA2+ from the cell
  • in the cerebellar cortex, ATP2B2 and ATP2B3 were at highest levels within synaptic profiles, but ATP2B2 was postsynaptic and ATP2B3 was presynaptic
  • "fast" calcium transporter, which normally influences glutamate release from excitatory terminals where it helps control calcium levels
  • transporter protein critical for the clearance of calcium from excitable cells
  • having a major role for apical calcium transport
  • transports calcium across the apical surface of the cells into milk
  • can protect breast cancer cells from apoptosis and its expression in breast tumors correlates with clinical outcome
  • extrude Ca2+ from cells, maintaining the resting level of intracellular Ca2+ and controlling the Ca2+ transients induced by agonists
  • importance of ATP2B2 in Ca(2+) signaling, glutamate receptor expression and survival of Purkinje cells
  • ATP2B2 activity is an important regulator of the dendritic calcium equilibrium controlling Purkinje cell dendritic growth
  • is necessary for auditory transduction and serves as the primary Ca(2+) extrusion mechanism in auditory stereocilia bundles
  • critical auditory protein that may be involved in normal maturation of auditory sensitivity after the onset of hearing
  • ATP2B2, ATP2B3 are mainly responsible for transport of protons to intracellular milieu
  • ATP2B2, ATP2B3 respond to a rapid removal of Ca(2+) and are expressed predominantly in excitable cells
  • in the lactating mammary gland, the plasma membrane calcium ATPase2 (ATP2B2) transports milk calcium
  • calcium pump that plays important roles in neuronal function
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interactions between ATP2B2 and ERBB2 in specific actin-rich membrane domains
  • SLC9A3R1 acts with ATP2B2 to regulate ERBB2 signaling and membrane retention in breast cancers
  • ERBB2 interact with the chaperone, HSP90AB1, and the calcium pump, ATP2B2, within specific plasma membrane domains that protrude from the cell surface
  • during lactation, SLC9A3R1 is required for the proper expression and apical localization of ATP2B2, which, in turn, contributes to preventing the premature activation of STAT3 and the lysosome-mediated cell death pathway that usually occur only early in mammary involution
  • cell & other
    REGULATION
    Other down-regulating ATP2B2, prolonged distension of the alveoli of mammary gland, overloads the calcium-buffering capacity of the cells causing a sustained increase in intracellular calcium and apoptosis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    with mutation of CDH23, leading to sensorineural deafness
    constitutional     --low  
    down-regulated early in mammary involution associated with changes in mammary epithelial cell shape
    tumoral     --over  
    in breast cancers is associated with poor outcome
    constitutional     --low  
    such as occurs in aging brain likely leads to subtle disruptions in normal Ca(2+) signaling and enhanced susceptibility to stresses that can alter the regulation of Ca(2+) homeostasis
    Susceptibility
    Variant & Polymorphism variant may modify the severity of sensorineural hearing loss caused by a variety of factors
    Candidate gene for sensorineural hearing loss in 3p25 deletion
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    interactions between ATP2B2 and ERBB2 may represent therapeutic targets for breast cancer
    cancerreproductivebreast
    interactions between ATP2B2 and ERBB2 may represent therapeutic targets for breast cancer
    ANIMAL & CELL MODELS
  • mouse mutation, Tommy, causes a non-conservative Glu629Lys change in the second intracellular loop of the pump which harbors the active site, leading to profound hearing impairment from P18, with significant differences in hearing thresholds between wild type and heterozygotes
  • Atp2b2 murine mutant overexpressed in model cells displayed an evident defect both in the basal activity of the pump and in the long range ejection of Ca(2+), the human mutant instead failed to impair the Ca(2+) ejection by the pump