Plasma membrane calcium-transporting ATPase 1 (ATP2B1)
The protein contains 1258 amino acids for an estimated molecular weight of 138755 Da.
Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis. Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction. Positively regulates bone mineralization through absorption of calcium from the intestine. Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts (By similarity). Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells (PubMed:29104511). May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles. (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| empty |
Biological Process
Aging
Blood coagulation
Brain development
Calcium ion export across plasma membrane
Cellular calcium ion homeostasis
Cellular response to corticosterone stimulus
Cellular response to vitamin D
Ion transmembrane transport
Negative regulation of cytokine production
Negative regulation of cytosolic calcium ion concentration
Neural retina development
Positive regulation of bone mineralization
Positive regulation of calcium ion transport
Regulation of blood pressure
Regulation of cardiac conduction
Regulation of cellular response to insulin stimulus
Regulation of cytosolic calcium ion concentration
Regulation of vascular associated smooth muscle contraction
Response to cold
Transmembrane transport
Transport
Cellular Component
Apical plasma membrane
Basolateral plasma membrane
Cell junction
Cytoplasmic side of plasma membrane
Dendritic spine membrane
Extracellular exosome
GABA-ergic synapse
Glutamatergic synapse
Immunological synapse
Integral component of plasma membrane
Integral component of presynaptic active zone membrane
Intracellular membrane-bounded organelle
Membrane
Membrane raft
Neuronal cell body membrane
Nucleoplasm
Nucleus
Obsolete cell
Plasma membrane
Molecular Function
ATP binding
ATPase
ATPase-coupled cation transmembrane transporter activity
Calcium ion transmembrane transporter activity
Calmodulin binding
Metal ion binding
P-type calcium transporter activity
P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration
PDZ domain binding
The reference OMIM entry for this protein is 108731
Atpase, ca(2+)-transporting, plasma membrane, 1; atp2b1
Plasma membrane ca(2+)-atpase, type 1; pmca1
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at least 4 genes: ATP2B1; ATP2B2 (108733) on chromosome 3p26; ATP2B3 (300014) on Xq28; and ATP2B4 (108732) on 1q25. The diversity of these enzymes is further increased by alternative splicing of transcripts.CLONING
Verma et al. (1988) isolated a cDNA corresponding to a Ca(2+) plasma membrane pump from a human teratoma cDNA library. The 1,220-amino acid protein has a calculated molecular mass of 134.6 kD. The translated sequence contains a putative calmodulin-binding domain near the C terminus and domains matching those of cAMP-dependent protein kinase substrates. Kumar et al. (1993) isolated a cDNA corresponding to the ATP2B1 gene from a human osteoblast cDNA library. The cDNA encoded a deduced 1,220-amino acid protein. Brandt et al. (1992) described 4 PMCA1 splice variants, which they referred to as PMCA1a through PMCA1d, and examined their expression using PCR. PMCA1a was expressed in spinal cord, brain, skeletal muscle, and heart. PMCA1b was expressed in all tissues examined. PMCA1c was expressed in skeletal muscle, heart, spinal cord, and brain. PMCA1d was expressed in heart and skeletal muscle. By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of the PMCA and SERCA (see 108730) genes during human fetal heart development. PMCA1 and PMCA4 (ATP2B4) were expressed in 8-, 12-, and 20-week fetal heart and in adult heart. Okunade et al. (2004) examined Pmca1 and Pmca4 expression in mouse tissues. Pmca1 was expressed in all tissues examined, and Pmca4 was expressed in all tissues examined except liver. Pmca1 predominated in brain, intestine, kidney, lung, and stomach, whereas Pmca4 predominated in aorta, portal vein, bladder, diaphragm, seminal vesicles, and testis.GENE FUNCTION
The Ca(2+)-ATPases are members of the P class of ion-motive ATPases; they form an acylphosphate intermediate as part of the reaction mechanism. PMCA removes bivalent calcium ions from eukaryotic cells and plays a critical role in intracellular calcium homeostasis by its capacity for removing calcium ions from cells against very large concentration gradients (Olson et al., 1991). Mammalian PMCA1 is expressed in calcium-transporting epithelia and bone mesenchymal cells, and it is upregulated by 1,25-dihydroxyvitamin D3 in both tissues. Glendenning et al. (2000) presented evidence showing tissue-specific sensitivity of the PMCA1 promoter to direct transcriptional downregulation by 1,25-dihydroxyvitamin D3. Their results suggested that any positive regulatory vitamin D response element in PMCA1 must lie outside the core promoter.GENE STRUCTURE
Hilfiker et al. (1993) determined that the PMCA1 gene contains 22 exons and a putative alternative exon 1 that they called exon 1*. The ATG start codon is in exon 2. The promoter and 5-prime flanking region is embedded in a CpG island and is characterized by numerous Sp1 (189906)-binding sites and the absence of a TATA box. The PMCA1 gene spans more than 100 kb.MAPPING
Olson et al. (1991) mapped the ATP2B1 gene to chromosome 12q21-q23 by 3 independent methods: Southern analysis of human-rodent somatic cell hybrids, in situ hybridization of human metaphase spreads, and genetic linkage analysis in the CEPH pedigrees.ANIMAL MODEL
Okunade et al. (2004) found that loss of both copies of the Atp2b1 gene caused embryonic lethality in mice, whereas heterozygous mutants had ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 108731 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed