ATP2A3 explained

Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 is an enzyme that in humans is encoded by the ATP2A3 gene.^{[1] [2]}

This gene encodes one of the SERCA Ca²⁺-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of cells. SERCA3 expression was originally described as non-muscular, but was recently observed in cardiomyocyte. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in 6 transcript variants encoding different isoforms named SERCA3a to SERCA3f.^[2]

Cancer

ATP2A3 gene has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy.^[3] For this reason, ATP2A3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.^[3]

Further reading

• Wuytack F, Papp B, Verboomen H . A sarco/endoplasmic reticulum Ca²⁺-ATPase 3-type Ca²⁺ pump is expressed in platelets, in lymphoid cells, and in mast cells . J. Biol. Chem. . 269 . 2 . 1410–6 . 1994 . 10.1016/S0021-9258(17)42273-3 . 8288608 . etal. free .
• Dode L, De Greef C, Mountain I . Structure of the human sarco/endoplasmic reticulum Ca²⁺-ATPase 3 gene. Promoter analysis and alternative splicing of the SERCA3 pre-mRNA . J. Biol. Chem. . 273 . 22 . 13982–94 . 1998 . 9593748 . 10.1074/jbc.273.22.13982 . etal. free .
• Poch E, Leach S, Snape S . Functional characterization of alternatively spliced human SERCA3 transcripts . Am. J. Physiol. . 275 . 6 Pt 1 . C1449–58 . 1999 . 9843705 . 10.1152/ajpcell.1998.275.6.C1449. etal. free .
• Martin V, Bredoux R, Corvazier E . Three novel sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) 3 isoforms. Expression, regulation, and function of the membranes of the SERCA3 family . J. Biol. Chem. . 277 . 27 . 24442–52 . 2002 . 11956212 . 10.1074/jbc.M202011200 . etal. free .
• Gélébart P, Kovács T, Brouland JP . Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during differentiation . J. Biol. Chem. . 277 . 29 . 26310–20 . 2002 . 11986315 . 10.1074/jbc.M201747200 . etal. free .
• Dode L, Vilsen B, Van Baelen K . Dissection of the functional differences between sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) 1 and 3 isoforms by steady-state and transient kinetic analyses . J. Biol. Chem. . 277 . 47 . 45579–91 . 2003 . 12207029 . 10.1074/jbc.M207778200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Houston R . Longitudinal sections of unfixed muscle . Biotechnic & Histochemistry . 77 . 4 . 229–30 . 2003 . 12503734 .
• Borge PD, Wolf BA . Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium ATPase 3 in insulin-secreting beta-cells . J. Biol. Chem. . 278 . 13 . 11359–68 . 2003 . 12524443 . 10.1074/jbc.M209521200 . free .
• Chandrasekera CP, Lytton J . Inhibition of human SERCA3 by PL/IM430. Molecular analysis of the interaction . J. Biol. Chem. . 278 . 14 . 12482–8 . 2003 . 12540840 . 10.1074/jbc.M212745200 . free .
• Gevaert K, Goethals M, Martens L . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nat. Biotechnol. . 21 . 5 . 566–9 . 2004 . 12665801 . 10.1038/nbt810 . 23783563 . etal.
• Bobe R, Bredoux R, Corvazier E . Identification, expression, function, and localization of a novel (sixth) isoform of the human sarco/endoplasmic reticulum Ca²⁺ATPase 3 gene . J. Biol. Chem. . 279 . 23 . 24297–306 . 2004 . 15028735 . 10.1074/jbc.M314286200 . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Brouland JP, Gélébart P, Kovàcs T . The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis . Am. J. Pathol. . 167 . 1 . 233–42 . 2005 . 15972967 . 10.1016/S0002-9440(10)62968-9. 1603437 . etal.
• Hadri L, Pavoine C, Lipskaia L . Transcription of the sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase type 3 gene, ATP2A3, is regulated by the calcineurin/NFAT pathway in endothelial cells . Biochem. J. . 394 . Pt 1 . 27–33 . 2006 . 16250893 . 10.1042/BJ20051387 . 1385999 . etal.
• Wootton LL, Michelangeli F . The effects of the phenylalanine 256 to valine mutation on the sensitivity of sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA) Ca²⁺ pump isoforms 1, 2, and 3 to thapsigargin and other inhibitors . J. Biol. Chem. . 281 . 11 . 6970–6 . 2006 . 16410239 . 10.1074/jbc.M510978200 . free .
• Chaâbane C, Corvazier E, Bredoux R . Sarco/endoplasmic reticulum Ca²⁺ATPase type 3 isoforms (SERCA3b and SERCA3f): distinct roles in cell adhesion and ER stress . Biochem. Biophys. Res. Commun. . 345 . 4 . 1377–85 . 2006 . 16725111 . 10.1016/j.bbrc.2006.05.054 . etal.
• Bredoux R, Corvazier E, Dally S . Human platelet Ca²⁺-ATPases: new markers of cell differentiation as illustrated in idiopathic scoliosis . Platelets . 17 . 6 . 421–33 . 2006 . 16973504 . 10.1080/09537100600758719 . 24473757 . etal.
• Ewing RM, Chu P, Elisma F . Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 . etal.

Notes and References

1. Dode L, Wuytack F, Kools PF, Baba-Aissa F, Raeymaekers L, Brike F, van de Ven WJ, Casteels R . cDNA cloning, expression and chromosomal localization of the human sarco/endoplasmic reticulum Ca²⁺-ATPase 3 gene . Biochem J . 318 . 2. 689–99 . Nov 1996 . 8809064 . 1217674 . 10.1042/bj3180689.
2. Web site: Entrez Gene: ATP2A3 ATPase, Ca++ transporting, ubiquitous.
3. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808 . 11392/2066612 . 24986454 .