Plasma membrane calcium-transporting ATPase 3 (ATP2B3)

The protein contains 1220 amino acids for an estimated molecular weight of 134197 Da.

 

ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels at the presynaptic terminals (PubMed:25953895, PubMed:27035656, PubMed:22912398, PubMed:18029012). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment (PubMed:25953895, PubMed:27035656). May counter-transport protons, but the mechanism and the stoichiometry of this Ca(2+)/H(+) exchange remains to be established (By similarity). (updated: June 2, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.

Topcons

Interpro domains
Total structural coverage: 25%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs2269409
SCAX1
SCAX1; the mutant protein is expressed at the plasma membrane, but shows impaired extrusion of intracellular calcium

The reference OMIM entry for this protein is 300014

Atpase, ca(2+)-transporting, plasma membrane, 3; atp2b3
Plasma membrane ca(2+)-atpase, type 3; pmca3

DESCRIPTION

The ATP2B3 gene encodes a calcium-transporting ATPase predominantly expressed in the brain (summary by Brown et al., 1996). The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at least 4 genes: ATP2B1 (108731) on chromosome 12q21; ATP2B2 (108733) on 3p26; ATP2B3; and ATP2B4 (108732) on 1q25.

CLONING

Stahl et al. (1992) showed that the products of the rat ATP2B2 and ATP2B3 genes are particularly abundant in some brain regions. By PCR, Brandt et al. (1992) detected human PMCA3 expression in spinal cord and brain. A splice variant, PMCA3b, was expressed in adrenal gland, spinal cord, and brain. The presence of 3 other PCR products, primarily in spinal cord, suggested the presence of additional alternatively spliced variants. Brown et al. (1996) isolated 2 main isoforms for the ATP2B3 cDNA, designated 3a and 3b, which encode 1,173- and 1,220-amino acid proteins, respectively. Northern blot analysis detected a 7-kb mRNA transcript exclusively in the brain. Zanni et al. (2012) found high expression of the full-length ATP2B3 isoform in presynaptic terminals of parallel fibers-Purkinje neurons in the cerebellum.

MAPPING

By fluorescence in situ hybridization, analysis of somatic cell hybrids, and genetic linkage analysis of CEPH families, Wang et al. (1994) mapped the ATP2B3 gene to chromosome Xq28.

MOLECULAR GENETICS

In affected members of the family with early-onset X-linked spinocerebellar ataxia-1 (SCAX1; 302500) originally reported by Bertini et al. (2000), Zanni et al. (2012) identified a mutation in the ATP2B3 (G1107D; 300014.0001). The mutation was identified by X-exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies showed that the mutant protein had defective intracellular calcium clearance compared to wildtype, suggesting that the disorder resulted from defective calcium homeostasis in neurons. - Somatic Mutation Beuschlein et al. (2013) performed exome sequencing of aldosterone-producing adenomas and identified somatic hotspot mutations in the ATP1A1 (182310) gene, encoding a sodium/potassium ATPase alpha subunit, and the ATP2B3 gene, encoding a calcium ATPase, in 3 and 2 of the 9 aldosterone-producing adenomas, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium, and calcium ion homeostasis. Functional in vitro studies of the ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiologic ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 aldosterone-producing adenomas, Beuschlein et al. (2013) found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations, and lower potassium concentrations compared with mutation-negative cases. ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for ATP2B3

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300014 was added.