ATP2B2 (ATPase plasma membrane Ca2+ transporting 2)

Gene

• Entrez ID: 491
• Gene name: ATPase plasma membrane Ca2+ transporting 2
• Gene symbol: ATP2B2
• Synonyms: PMCA2, PMCA2a, PMCA2i
• Chromosome: 3
• Chromosome location: 3p25.3
• Summary: The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 2. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61736451	C>A,T	Risk-factor, benign	Coding sequence variant, missense variant
rs1064795322	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1575005369	->G	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1575009907	C>T	Likely-pathogenic	Splice acceptor variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IBA	21873635
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	NAS	1313367
GO:0005515	Function	Protein binding	IPI	11786550, 17689535, 30126976
GO:0005516	Function	Calmodulin binding	IEA
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	15765049
GO:0005886	Component	Plasma membrane	NAS	1313367
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0006816	Process	Calcium ion transport	IMP	17234811
GO:0006816	Process	Calcium ion transport	NAS	1313367
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0007605	Process	Sensory perception of sound	IMP	15829536, 17234811
GO:0019829	Function	ATPase-coupled cation transmembrane transporter activity	IBA	21873635
GO:0030165	Function	PDZ domain binding	IBA	21873635
GO:0030182	Process	Neuron differentiation	IDA	11259493
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0046872	Function	Metal ion binding	IEA
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IMP	17234811
GO:0070062	Component	Extracellular exosome	HDA	18570454
GO:0070588	Process	Calcium ion transmembrane transport	IEA
GO:0098793	Component	Presynapse	IEA
GO:0098839	Component	Postsynaptic density membrane	IBA	21873635
GO:0098978	Component	Glutamatergic synapse	IDA	7929331
GO:0098978	Component	Glutamatergic synapse	IMP	7929331
GO:0098982	Component	GABA-ergic synapse	IDA	7929331
GO:0098982	Component	GABA-ergic synapse	IMP	7929331
GO:0099509	Process	Regulation of presynaptic cytosolic calcium ion concentration	IEA
GO:0099566	Process	Regulation of postsynaptic cytosolic calcium ion concentration	IEA
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1905056	Function	Calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration	IMP	7929331
GO:1905059	Function	Calcium-transporting ATPase activity involved in regulation of postsynaptic cytosolic calcium ion concentration	IDA	7929331
GO:1905059	Function	Calcium-transporting ATPase activity involved in regulation of postsynaptic cytosolic calcium ion concentration	IMP	7929331

Other IDs

• MIM: 108733
• HGNC: 815
• e!Ensembl: ENSG00000157087

Protein

• UniProt ID: Q01814
• Protein name: Plasma membrane calcium-transporting ATPase 2 (PMCA2) (EC 7.2.2.10) (Plasma membrane calcium ATPase isoform 2) (Plasma membrane calcium pump isoform 2)
• Protein function: ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:17234811, PubMed:15829536). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment (PubMed:17234811, PubMed:15829536). Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics. At parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+) efflux in response to climbing fiber-induced Ca(2+) rise. Provides for fast return of Ca(2+) concentrations back to their resting levels, ultimately contributing to long-term depression induction and motor learning (By similarity). Plays an essential role in hearing and balance (PubMed:17234811, PubMed:15829536). In cochlear hair cells, shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates Ca(2+) transients generated by the opening of the mechanoelectrical transduction channels. Regulates Ca(2+) levels in the vestibular system, where it contributes to the formation of otoconia (PubMed:17234811, PubMed:15829536). In non-excitable cells, regulates Ca(2+) signaling through spatial control of Ca(2+) ions extrusion and dissipation of Ca(2+) transients generated by store-operated channels (PubMed:25690014). In lactating mammary gland, allows for the high content of Ca(2+) ions in the milk (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00690	Cation_ATPase_N	48 → 118	Cation transporter/ATPase, N-terminus	Domain
  PF00122	E1-E2_ATPase	187 → 305		Family
  PF00122	E1-E2_ATPase	373 → 477		Family
  PF13246	Cation_ATPase	538 → 638		Family
  PF00689	Cation_ATPase_C	902 → 1084	Cation transporting ATPase, C-terminus	Family
  PF12424	ATP_Ca_trans_C	1126 → 1172	Plasma membrane calcium transporter ATPase C terminal	Family

• Sequence:

  MGDMTNSDFYSKNQRNESSHGGEFGCTMEELRSLMELRGTEAVVKIKETYGDTEAICRRL
  KTSPVEGLPGTAPDLEKRKQIFGQNFIPPKKPKTFLQLVWEALQDVTLIILEIAAIISLG
  LSFYHPPGEGNEGCATAQGGAEDEGEAEAGWIEGAAILLSVICVVLVTAFNDWSKEKQFR
  GLQSRIEQEQKFTVVRAGQVVQIPVAEIVVGDIAQVKYGDLLPADGLFIQGNDLKIDESS
  LTGESDQVRKSVDKDPMLLSGTHVMEGSGRMLVTAVGVNSQTGIIFTLLGAGGEEEEKKD
  KKGVKKGDGLQLPAADGAAASNAADSANASLVNGKMQDGNVDASQSKAKQQDGAAAMEMQ
  PLKSAEGGDADDRKKASMHKKEKSVLQGKLTKLAVQIGKAGLVMSAITVIILVLYFTVDT
  FVVNKKPWLPECTPVYVQYFVKFFIIGVTVLVVAVPEGLPLAVTISLAYSVKKMMKDNNL
  VRHLDACETMGNATAICSDKTGTLTTNRMTVVQAYVGDVHYKEIPDPSSINTKTMELLIN
  AIAINSAYTTKILPPEKEGALPRQVGNKTECGLLGFVLDLKQDYEPVRSQMPEEKLYKVY
  TFNSVRKSMSTVIKLPDESFRMYSKGASEIVLKKCCKILNGAGEPRVFRPRDRDEMVKKV
  IEPMACDGLRTICVAYRDFPSSPEPDWDNENDILNELTCICVVGIEDPVRPEVPEAIRKC
  QRAGITVRMVTGDNINTARAIAIKCGIIHPGEDFLCLEGKEFNRRIRNEKGEIEQERIDK
  IWPKLRVLARSSPTDKHTLVKGIIDSTHTEQRQVVAVTGDGTNDGPALKKADVGFAMGIA
  GTDVAKEASDIILTDDNFSSIVKAVMWGRNVYDSISKFLQFQLTVNVVAVIVAFTGACIT
  QDSPLKAVQMLWVNLIMDTFASLALATEPPTETLLLRKPYGRNKPLISRTMMKNILGHAV
  YQLALIFTLLFVGEKMFQIDSGRNAPLHSPPSEHYTIIFNTFVMMQLFNEINARKIHGER
  NVFDGIFRNPIFCTIVLGTFAIQIVIVQFGGKPFSCSPLQLDQWMWCIFIGLGELVWGQV
  IATIPTSRLKFLKEAGRLTQKEEIPEEELNEDVEEIDHAERELRRGQILWFRGLNRIQTQ
  IRVVKAFRSSLYEGLEKPESRTSIHNFMAHPEFRIEDSQPHIPLIDDTDLEEDAALKQNS
  SPPSSLNKNNSAIDSGINLTTDTSKSATSSSPGSPIHSLETSL

• Sequence length: 1243