Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
Also known as: ATP2A2, ATP2B
Function
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation. Also modulates ER contacts with lipid droplets, mitochondria and endosomes. In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity).
Classification
- Family (Pfam)
- PF13246 Cation_ATPase, PF00689 Cation_ATPase_C, PF00690 Cation_ATPase_N, PF00122 E1-E2_ATPase, PF08282 Hydrolase_3
- InterPro
- ATPase_P-typ_cation-transptr_C, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cyto_dom_N, ATPase_P-typ_P_site, ATPase_P-typ_TM_dom_sf, ATPase_P-typ_transduc_dom_A_sf, ATPase_P-type_domA, HAD-like_sf, HAD_sf, P-type_ATPase_IIA, P_typ_ATPase, P_typ_ATPase_HD_dom
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 15
- 5ZTF X-ray 3.45A
- 6JJU X-ray 3.20A
- 6LLE EM 2.90A
- 6LLY EM 2.80A
- 6LN5 EM 2.80A
- 6LN6 EM 2.90A
- 6LN7 EM 2.80A
- 6LN8 EM 3.10A
- 6LN9 EM 3.40A
- 7BT2 X-ray 3.00A
- 7E7S EM 3.30A
- 7W7T EM 3.40A
- … and 3 more
A predicted model is available from AlphaFold.
Gene Ontology · 42
- GO:0090534 calcium ion-transporting ATPase complex
- GO:0005783 endoplasmic reticulum
- GO:0005789 endoplasmic reticulum membrane
- GO:0014801 longitudinal sarcoplasmic reticulum
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0031095 platelet dense tubular network membrane
- GO:0097470 ribbon synapse
- GO:0016529 sarcoplasmic reticulum
- GO:0033017 sarcoplasmic reticulum membrane
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0005246 calcium channel regulator activity
- GO:0005509 calcium ion binding
- GO:0019899 enzyme binding
- GO:0106222 lncRNA binding
- GO:0005388 P-type calcium transporter activity
- GO:0086039 P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential
- GO:0044548 S100 protein binding
- GO:0044325 transmembrane transporter binding
- GO:0000045 autophagosome assembly
- GO:0016240 autophagosome membrane docking
- GO:1990036 calcium ion import into sarcoplasmic reticulum
- GO:0070588 calcium ion transmembrane transport
- GO:1903515 calcium ion transport from cytosol to endoplasmic reticulum
- GO:0007155 cell adhesion
- GO:0032469 endoplasmic reticulum calcium ion homeostasis
- GO:0008544 epidermis development
- GO:0006874 intracellular calcium ion homeostasis
- GO:1990456 mitochondrion-endoplasmic reticulum membrane tethering
- GO:0034220 monoatomic ion transmembrane transport
- GO:0003012 muscle system process
- GO:0140056 organelle localization by membrane tethering
- GO:0032470 positive regulation of endoplasmic reticulum calcium ion concentration
- GO:0010460 positive regulation of heart rate
- GO:1903779 regulation of cardiac conduction
- GO:0098909 regulation of cardiac muscle cell action potential involved in regulation of contraction
- GO:0086036 regulation of cardiac muscle cell membrane potential
- GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling
- GO:0055119 relaxation of cardiac muscle
- GO:0034976 response to endoplasmic reticulum stress
- GO:0070296 sarcoplasmic reticulum calcium ion transport
Disease associations
- acrokeratosis verruciformis MONDO:0007048
- Darier disease MONDO:0007417
- rhabdomyolysis, susceptibility to, 2 MONDO:0980721
Drugs targeting this protein · 2
- ISTAROXIME activator
- MIPSAGARGIN inhibitor
Related proteins · sequence + function similarity
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1.00
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a 0.99
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 0.99
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 0.99
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 0.98
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 0.98
Co-cited proteins · studied together in the literature
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a 1 shared papers
- Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF 2 shared papers
- Calcium-transporting ATPase type 2C member 1 1 shared papers
- Thioredoxin-related transmembrane protein 1 1 shared papers
- Thioredoxin-related transmembrane protein 2 1 shared papers
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 1 shared papers
- Superoxide dismutase [Mn], mitochondrial 1 shared papers
- Phospholamban 3 shared papers
- Translocating chain-associated membrane protein 2 1 shared papers
- HCLS1-associated protein X-1 1 shared papers
- Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator ARLN 1 shared papers
- Endoregulin 1 shared papers
Literature · 34 cited papers
- Dominant rhabdomyolysis linked to a recurrent ATP2A2 variant reducing SERCA2 function in muscle. Brain · 2025
- Micropeptide hetero-oligomerization adds complexity to the calcium pump regulatory network. Biophys. J. · 2023
- The transmembrane peptide DWORF activates SERCA2a via dual mechanisms. J. Biol. Chem. · 2021
- TMX2 is a crucial regulator of cellular redox state, and its dysfunction causes severe brain developmental abnormalities. Am. J. Hum. Genet. · 2019
- The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. Mol. Cell · 2017
- Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 associated with Darier disease and Hailey-Hailey disease. Hum. Mutat. · 2017
- TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux. J. Cell Biol. · 2016
- TMEM203 is a novel regulator of intracellular calcium homeostasis and is required for spermatogenesis. PLoS ONE · 2015
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Novel ATP2A2 mutations in a large sample of individuals with Darier disease. J. Dermatol. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- … and 22 more in the literature graph
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