Plasma membrane calcium-transporting ATPase 4 is an enzyme that in humans is encoded by the ATP2B4 gene.[5][6]

Available structures
PDBOrtholog search: PDBe RCSB
AliasesATP2B4, ATP2B2, MXRA1, PMCA4, PMCA4b, PMCA4x, ATPase plasma membrane Ca2+ transporting 4
External IDsOMIM: 108732 MGI: 88111 HomoloGene: 48034 GeneCards: ATP2B4
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1q32.1Start203,626,561 bp[1]
End203,744,081 bp[1]
RNA expression pattern

More reference expression data









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 203.63 – 203.74 MbChr 1: 133.7 – 133.8 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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.[6]


ATP2B4 has been shown to interact with CASK.[7]


  1. GRCh38: Ensembl release 89: ENSG00000058668 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000026463 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Olson S, Wang MG, Carafoli E, Strehler EE, McBride OW (April 1991). "Localization of two genes encoding plasma membrane Ca2(+)-transporting ATPases to human chromosomes 1q25-32 and 12q21-23". Genomics. 9 (4): 629–41. doi:10.1016/0888-7543(91)90356-J. PMID 1674727.
  6. "Entrez Gene: ATP2B4 ATPase, Ca++ transporting, plasma membrane 4".
  7. Schuh K, Uldrijan S, Gambaryan S, Roethlein N, Neyses L (March 2003). "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. doi:10.1074/jbc.M212507200. PMID 12511555.

Further reading

  • Møller JV, Juul B, le Maire M (May 1996). "Structural organization, ion transport, and energy transduction of P-type ATPases". Biochimica et Biophysica Acta. 1286 (1): 1–51. doi:10.1016/0304-4157(95)00017-8. PMID 8634322.
  • Strehler EE, Zacharias DA (January 2001). "Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps". Physiological Reviews. 81 (1): 21–50. doi:10.1152/physrev.2001.81.1.21. PMID 11152753.
  • Strehler EE, Treiman M (May 2004). "Calcium pumps of plasma membrane and cell interior". Current Molecular Medicine. 4 (3): 323–35. doi:10.2174/1566524043360735. PMID 15101689.
  • Heim R, Hug M, Iwata T, Strehler EE, Carafoli E (April 1992). "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. doi:10.1111/j.1432-1033.1992.tb16784.x. PMID 1313367.
  • Brandt P, Neve RL, Kammesheidt A, Rhoads RE, Vanaman TC (March 1992). "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. PMID 1531651.
  • Strehler EE, James P, Fischer R, Heim R, Vorherr T, Filoteo AG, Penniston JT, Carafoli E (February 1990). "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. PMID 2137451.
  • James P, Maeda M, Fischer R, Verma AK, Krebs J, Penniston JT, Carafoli E (February 1988). "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. PMID 2963820.
  • Brandt P, Zurini M, Neve RL, Rhoads RE, Vanaman TC (May 1988). "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. Bibcode:1988PNAS...85.2914B. doi:10.1073/pnas.85.9.2914. PMC 280113. PMID 2966397.
  • Howard A, Barley NF, Legon S, Walters JR (October 1994). "Plasma-membrane calcium-pump isoforms in human and rat liver". The Biochemical Journal. 303 ( Pt 1) (Pt 1): 275–9. doi:10.1042/bj3030275. PMC 1137587. PMID 7945253.
  • Stauffer TP, Hilfiker H, Carafoli E, Strehler EE (December 1994). "Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes". The Journal of Biological Chemistry. 269 (50): 32022. PMID 7989379.
  • Stauffer TP, Hilfiker H, Carafoli E, Strehler EE (December 1993). "Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes". The Journal of Biological Chemistry. 268 (34): 25993–6003. PMID 8245032.
  • Váradi A, Molnár E, Ashcroft SJ (March 1996). "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. doi:10.1042/bj3140663. PMC 1217098. PMID 8670083.
  • Santiago-García J, Mas-Oliva J, Saavedra D, Zarain-Herzberg A (February 1996). "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. doi:10.1007/BF00229314. PMID 8700162.
  • Zacharias DA, DeMarco SJ, Strehler EE (April 1997). "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. doi:10.1016/S0169-328X(97)00009-0. PMID 9105688.
  • Dean WL, Chen D, Brandt PC, Vanaman TC (June 1997). "Regulation of platelet plasma membrane Ca2+-ATPase by cAMP-dependent and tyrosine phosphorylation". The Journal of Biological Chemistry. 272 (24): 15113–9. doi:10.1074/jbc.272.24.15113. PMID 9182531.
  • Kim E, DeMarco SJ, Marfatia SM, Chishti AH, Sheng M, Strehler EE (January 1998). "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. doi:10.1074/jbc.273.3.1591. PMID 9430700.
  • Guerini D, García-Martin E, Gerber A, Volbracht C, Leist M, Merino CG, Carafoli E (January 1999). "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. doi:10.1074/jbc.274.3.1667. PMID 9880546.
  • Rosado JA, Sage SO (June 2000). "Regulation of plasma membrane Ca2+-ATPase by small GTPases and phosphoinositides in human platelets". The Journal of Biological Chemistry. 275 (26): 19529–35. doi:10.1074/jbc.M001319200. PMID 10748016.
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