Reactome | ATP2A1-3 transport Ca2+ from cytosol to ER lumen

ATP2A1-3 transport Ca2+ from cytosol to ER lumen

Stable Identifier

R-HSA-427910

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane

Synonyms

Sequestration of Ca2+ to intracellular stores

ReviewStatus

5/5

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ATP2A1-3 transport Ca2+ from cytosol to ER lumen

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Intracellular pools of Ca2+ serve as the source for inositol 1,4,5-trisphosphate (IP3) -induced alterations in cytoplasmic free Ca2+. In most human cells Ca2+ is stored in the lumen of the sarco/endoplastic reticulum by ATPases known as SERCAs (ATP2As). In platelets, ATP2As transport Ca2+ into the platelet dense tubular network. ATP2As are P-type ATPases, similar to the plasma membrane Na+ and Ca+-ATPases. Humans have three genes for SERCA pumps; ATP2A1-3. Studies on ATP2A1 suggest that it binds two Ca2+ ions from the cytoplasm and is subsequently phosphorylated at Asp351 before translocating Ca2+ into the SR lumen. There is a counter transport of two or possibly three protons ensuring partial charge balancing. Sarcolipin (SLN) can reversibly inhibit the activity of ATP2A1 by decreasing the apparent affinity of the ATPase for Ca2+ (Gorski et al. 2013) whereas activated Ca2+/CaM-dependent protein kinase II (CAMK2) and sorcin (SRI) can both stimulate ATP2A1-3 activity (Toyofuku et al. 1994, Matsumoto et al. 2005).

Literature References

PubMed ID	Title	Journal	Year
15754088	Sorcin interacts with sarcoplasmic reticulum Ca(2+)-ATPase and modulates excitation-contraction coupling in the heart Ikeda, Y, Inoue, N, Ohkusa, T, Sato, T, Hisamatsu, Y, Matsuzaki, M, Matsumoto, T, Suzuki, S	Basic Res. Cardiol.	2005
7702581	Localization and identification of Ca2+ATPases in highly purified human platelet plasma and intracellular membranes. Evidence that the monoclonal antibody PL/IM 430 recognizes the SERCA 3 Ca2+ATPase in human platelets Bokkala, S, Wuytack, F, el-Daher, SS, Kakkar, VV, Authi, KS	Biochem J	1995
23362265	Sarco(endo)plasmic reticulum calcium ATPase (SERCA) inhibition by sarcolipin is encoded in its luminal tail Gorski, PA, Young, HS, Vangheluwe, P, Glaves, JP	J. Biol. Chem.	2013
7929371	Identification of Ser38 as the site in cardiac sarcoplasmic reticulum Ca(2+)-ATPase that is phosphorylated by Ca2+/calmodulin-dependent protein kinase Toyofuku, T, MacLennan, DH, Curotto Kurzydlowski, K, Narayanan, N	J. Biol. Chem.	1994
2953725	Ca2+-activated ATPase in microsomes from human liver Heilmann, C, Gerok, W, Spamer, C	J Biol Chem	1987