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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	181.56 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001001331 23 - 8962 NP_001001331 - 1243 . clear apical and lateral distribution . a significant fraction partitioned into low-density membranes associated with lipid rafts 2007 19379709 also called W/B apical localization is lipid raft-dependent and sensitive to cholesterol depletion in the presence of SLC9A3R2, co-localized with the actin-binding protein ezrin even after disruption of the actin cytoskeleton by cytochalasin D or latrunculin B NM_001683 20 - 8827 NP_001674 132.5 1198 . mainly localized to the basolateral membrane 2007 19379709 also called Z/B

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner cochlea     Homo sapiens   ear inner       Homo sapiens Nervous brain hindbrain cerebellum   highly Homo sapiens   brain limbic system hippocampus     Homo sapiens Reproductive female system breast mammary gland   moderately Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer reproductive breast interactions between ATP2B2 and ERBB2 may represent therapeutic targets for breast cancer cancer reproductive breast 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