Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (ATP2A2)
The protein contains 1042 amino acids for an estimated molecular weight of 114757 Da.
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335).', 'Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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 predicted to be membranous by TOPCONS.
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Biological Process
Autophagosome assembly
Autophagosome membrane docking
Calcium ion import into sarcoplasmic reticulum
Calcium ion transmembrane transport
Calcium ion transport from cytosol to endoplasmic reticulum
Cardiac muscle hypertrophy in response to stress
Cell adhesion
Cellular calcium ion homeostasis
Cellular response to heat
Cellular response to oxidative stress
Endoplasmic reticulum calcium ion homeostasis
Epidermis development
ER-nucleus signaling pathway
Ion transmembrane transport
Mitochondrion-endoplasmic reticulum membrane tethering
Negative regulation of heart contraction
Negative regulation of receptor binding
Organelle localization by membrane tethering
Organelle organization
Positive regulation of endoplasmic reticulum calcium ion concentration
Positive regulation of heart rate
Regulation of calcium ion-dependent exocytosis of neurotransmitter
Regulation of cardiac conduction
Regulation of cardiac muscle cell action potential involved in regulation of contraction
Regulation of cardiac muscle cell membrane potential
Regulation of cardiac muscle contraction by calcium ion signaling
Regulation of the force of heart contraction
Relaxation of cardiac muscle
Response to endoplasmic reticulum stress
Response to lipopolysaccharide
Sarcoplasmic reticulum calcium ion transport
Skeletal muscle contraction
T-tubule organization
Transition between fast and slow fiber
Cellular Component
Apical ectoplasmic specialization
Calcium ion-transporting ATPase complex
Endoplasmic reticulum
Endoplasmic reticulum membrane
Extrinsic component of cytoplasmic side of plasma membrane
Integral component of plasma membrane
Longitudinal sarcoplasmic reticulum
Membrane
Obsolete cell
Perinuclear region of cytoplasm
Plasma membrane bounded cell projection
Platelet dense tubular network membrane
Protein-containing complex
Ribbon synapse
Sarcoplasmic reticulum
Sarcoplasmic reticulum membrane
Vesicle membrane
Molecular Function
ATP binding
ATPase
Calcium ion binding
Enzyme binding
Ion channel binding
Lutropin-choriogonadotropic hormone receptor binding
P-type calcium transporter activity
P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential
P-type proton-exporting transporter activity
Protein C-terminus binding
S100 protein binding
The reference OMIM entry for this protein is 101900
Acrokeratosis verruciformis; akv
Hopf disease
A number sign (#) is used with this entry because of evidence that acrokeratosis verruciformis is caused by heterozygous mutation in the ATP2A2 gene (108740) on chromosome 12q24, making it allelic to Darier disease (124200).
DESCRIPTION
Acrokeratosis verruciformis of Hopf is a localized disorder of keratinization affecting the distal extremities. Onset occurs early in life (Dhitavat et al., 2003).CLINICAL FEATURES
In the family with acrokeratosis verruciformis of Hopf reported by Niedelman (1947) and Niedelman and McKusick (1962), the dorsum of the hands was affected first and most conspicuously. Older individuals tended to have hyperkeratosis of the elbows and knees. The nails were pearly white in early years and become horny, brown, ridged, and grooved in later life. In older affected persons the palms and soles became involved. Although histology of acrokeratosis verruciformis lesions shows no evidence of dyskeratosis, Herndon and Wilson (1966) emphasized the phenotypic overlap between this entity and Darier-White disease (124200) and even proposed that they may not be separate entities. In the family they studied, 7 persons had typical acrokeratosis verruciformis, 1 or possibly 2 had Darier disease, and 3 had minor disturbances of keratinization (white nails from subungual hyperkeratosis, or punctate keratoses of palms or soles). Also see benign familial pemphigus (169600).INHERITANCE
The pedigree with acrokeratosis verruciformis studied by Niedelman (1947) and Niedelman and McKusick (1962) contained instances of male-to-male transmission as well as unaffected daughters of affected males, consistent with autosomal dominant inheritance.MOLECULAR GENETICS
Dhitavat et al. (2003) studied a family with acrokeratosis verruciformis in 6 generations and identified a heterozygous pro602-to-leu mutation in ATP2A2 (P602L; 108740.0011). This mutation predicted a nonconservative amino acid substitution in the ATP binding domain of the molecule. The mutation segregated with the disease phenotype in the family and was not found in 50 controls. Moreover, functional analysis of the P602L mutant showed that it had lost its ability to transport Ca(2+). This result demonstrated loss of function of the sarco(endo)plasmic reticulum Ca(2+) ATPase2 mutant in acrokeratosis verruciformis, thus providing evidence that acrokeratosis verruciformis and Darier disease are allelic disorders. ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 101900 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).