ATP2B4 explained

Plasma membrane calcium-transporting ATPase 4 is an enzyme that in humans is encoded by the ATP2B4 gene.^{[1] [2]}

The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified.

Interactions

ATP2B4 has been shown to interact with CASK.^[3]

Further reading

• Møller JV, Juul B, le Maire M . Structural organization, ion transport, and energy transduction of P-type ATPases . Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes . 1286 . 1 . 1–51 . May 1996 . 8634322 . 10.1016/0304-4157(95)00017-8 .
• Strehler EE, Zacharias DA . Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps . Physiological Reviews . 81 . 1 . 21–50 . January 2001 . 11152753 . 10.1152/physrev.2001.81.1.21 . 9062253 .
• Strehler EE, Treiman M . Calcium pumps of plasma membrane and cell interior . Current Molecular Medicine . 4 . 3 . 323–35 . May 2004 . 15101689 . 10.2174/1566524043360735 .
• Heim R, Hug M, Iwata T, Strehler EE, Carafoli E . Microdiversity of human-plasma-membrane calcium-pump isoform 2 generated by alternative RNA splicing in the N-terminal coding region . European Journal of Biochemistry . 205 . 1 . 333–40 . April 1992 . 1313367 . 10.1111/j.1432-1033.1992.tb16784.x . free .
• Brandt P, Neve RL, Kammesheidt A, Rhoads RE, Vanaman TC . Analysis of the tissue-specific distribution of mRNAs encoding the plasma membrane calcium-pumping ATPases and characterization of an alternately spliced form of PMCA4 at the cDNA and genomic levels . The Journal of Biological Chemistry . 267 . 7 . 4376–85 . March 1992 . 10.1016/S0021-9258(18)42846-3 . 1531651 . free .
• Strehler EE, James P, Fischer R, Heim R, Vorherr T, Filoteo AG, Penniston JT, Carafoli E . Peptide sequence analysis and molecular cloning reveal two calcium pump isoforms in the human erythrocyte membrane . The Journal of Biological Chemistry . 265 . 5 . 2835–42 . February 1990 . 10.1016/S0021-9258(19)39877-1 . 2137451 . free .
• James P, Maeda M, Fischer R, Verma AK, Krebs J, Penniston JT, Carafoli E . Identification and primary structure of a calmodulin binding domain of the Ca2+ pump of human erythrocytes . The Journal of Biological Chemistry . 263 . 6 . 2905–10 . February 1988 . 10.1016/S0021-9258(18)69154-9 . 2963820 . free .
• Brandt P, Zurini M, Neve RL, Rhoads RE, Vanaman TC . A C-terminal, calmodulin-like regulatory domain from the plasma membrane Ca2+-pumping ATPase . Proceedings of the National Academy of Sciences of the United States of America . 85 . 9 . 2914–8 . May 1988 . 2966397 . 280113 . 10.1073/pnas.85.9.2914 . 1988PNAS...85.2914B . free .
• Howard A, Barley NF, Legon S, Walters JR . Plasma-membrane calcium-pump isoforms in human and rat liver . The Biochemical Journal . 303 (Pt 1) . Pt 1 . 275–9 . October 1994 . 7945253 . 1137587 . 10.1042/bj3030275 .
• Stauffer TP, Hilfiker H, Carafoli E, Strehler EE . Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes . The Journal of Biological Chemistry . 269 . 50 . 32022 . December 1994 . 10.1016/S0021-9258(18)31797-6 . 7989379 . free .
• Stauffer TP, Hilfiker H, Carafoli E, Strehler EE . Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes . The Journal of Biological Chemistry . 268 . 34 . 25993–6003 . December 1993 . 10.1016/S0021-9258(19)74484-6 . 8245032 . free .
• Váradi A, Molnár E, Ashcroft SJ . A unique combination of plasma membrane Ca2+-ATPase isoforms is expressed in islets of Langerhans and pancreatic beta-cell lines . The Biochemical Journal . 314 (Pt 2) . Pt 2 . 663–9 . March 1996 . 8670083 . 1217098 . 10.1042/bj3140663 .
• Santiago-García J, Mas-Oliva J, Saavedra D, Zarain-Herzberg A . Analysis of mRNA expression and cloning of a novel plasma membrane Ca(2+)-ATPase splice variant in human heart . Molecular and Cellular Biochemistry . 155 . 2 . 173–82 . February 1996 . 8700162 . 10.1007/BF00229314 . 33539531 .
• Zacharias DA, DeMarco SJ, Strehler EE . mRNA expression of the four isoforms of the human plasma membrane Ca(2+)-ATPase in the human hippocampus . Brain Research. Molecular Brain Research . 45 . 1 . 173–6 . April 1997 . 9105688 . 10.1016/S0169-328X(97)00009-0 .
• Dean WL, Chen D, Brandt PC, Vanaman TC . Regulation of platelet plasma membrane Ca2+-ATPase by cAMP-dependent and tyrosine phosphorylation . The Journal of Biological Chemistry . 272 . 24 . 15113–9 . June 1997 . 9182531 . 10.1074/jbc.272.24.15113 . free .
• Kim E, DeMarco SJ, Marfatia SM, Chishti AH, Sheng M, Strehler EE . Plasma membrane Ca2+ ATPase isoform 4b binds to membrane-associated guanylate kinase (MAGUK) proteins via their PDZ (PSD-95/Dlg/ZO-1) domains . The Journal of Biological Chemistry . 273 . 3 . 1591–5 . January 1998 . 9430700 . 10.1074/jbc.273.3.1591 . free .
• Guerini D, García-Martin E, Gerber A, Volbracht C, Leist M, Merino CG, Carafoli E . The expression of plasma membrane Ca2+ pump isoforms in cerebellar granule neurons is modulated by Ca2+ . The Journal of Biological Chemistry . 274 . 3 . 1667–76 . January 1999 . 9880546 . 10.1074/jbc.274.3.1667 . free .
• Rosado JA, Sage SO . Regulation of plasma membrane Ca2+-ATPase by small GTPases and phosphoinositides in human platelets . The Journal of Biological Chemistry . 275 . 26 . 19529–35 . June 2000 . 10748016 . 10.1074/jbc.M001319200 . free .

Notes and References

1. Olson S, Wang MG, Carafoli E, Strehler EE, McBride OW . Localization of two genes encoding plasma membrane Ca2(+)-transporting ATPases to human chromosomes 1q25-32 and 12q21-23 . Genomics . 9 . 4 . 629–41 . April 1991 . 1674727 . 10.1016/0888-7543(91)90356-J .
2. Web site: Entrez Gene: ATP2B4 ATPase, Ca++ transporting, plasma membrane 4.
3. Schuh K, Uldrijan S, Gambaryan S, Roethlein N, Neyses L . Interaction of the plasma membrane Ca2+ pump 4b/CI with the Ca2+/calmodulin-dependent membrane-associated kinase CASK . The Journal of Biological Chemistry . 278 . 11 . 9778–83 . March 2003 . 12511555 . 10.1074/jbc.M212507200 . free .