High impact information on Atp2a3

• SERCA3b also co-immunoprecipitates with IRS-1 in wild-type and IRS-1-overexpressing beta-cell lines [1].
• Finally, overexpression of Ets-1 induced the expression of SERCA3 in endothelial cells and in fibroblasts [2].
• Analysis of the transcriptional activity of fragments of the SERCA3 promoter showed the existence of a minimal promoter region located between bases -97 and +153 that contains one ETS-binding site (EBS) and two Sp1 elements that are essential for basal transcription [2].
• We reported previously that the sarco(endo)plasmic reticulum Ca(2+)-ATPase type 3 (SERCA3) gene is expressed in many tissues and in a subset of cells such as endothelial, epithelial, and lymphoid lineages [2].
• The promoter of the murine SERCA3 gene was isolated, and a single transcription initiation site located 301 bp upstream of the translation initiation site was identified [2].

Biological context of Atp2a3

• Exon 21 (human, 101 base pairs; mouse, 86 base pairs) can be alternatively excluded, partially included, or totally included, thus generating, respectively, SERCA3a (human and mouse, 999 amino acids (aa)), SERCA3b (human, 1043 aa; mouse, 1038 aa), or SERCA3c (human, 1024 aa; mouse, 1021 aa) isoforms with different C termini [3].
• However, a lack of SERCA3 is insufficient in itself to alter glucose homeostasis or impair insulin secretion in mice [4].
• Characterization of the 3' end of the mouse SERCA 3 gene and tissue distribution of mRNA spliced variants [5].
• This results from a lack of progressive summation of rapid oscillations and from altered spontaneous electrical activity, i.e., lack of compound bursting, and membrane potential oscillations characterized by lower-frequency but larger-depolarization phases than observed in SERCA3+/+ beta-cells [6].

Anatomical context of Atp2a3

• The N89 antibodys used to identify the SERCA3 isoforms labelled cone outer segments, inner segments of photoreceptors and cell processes in the inner nuclear layer of the mouse retina [7].
• Here we analyzed the mechanisms involved in the regulation of transcription of the SERCA3 gene in endothelial cells [2].
• There are three isoforms of the sarcoplasmic reticulum Ca2+-ATPase; they are known as SERCA1, SERCA2, and SERCA3 [8].
• This suggests that, during the decay of each oscillation, the endoplasmic reticulum releases Ca(2+) that was pumped by SERCA3 during the upstroke phase [4].
• Two sarcoendoplasmic reticulum Ca(2+)-ATPases, SERCA3 and SERCA2b, are expressed in pancreatic islets [4].

Associations of Atp2a3 with chemical compounds

• However, basal and postprandial plasma glucose and insulin concentrations in SERCA3-deficient mice were normal [4].
• Ca(2+) mobilization by acetylcholine was normal in SERCA3-deficient beta-cells [4].
• Sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 3 (SERCA3), an isoform of the intracellular Ca(2+) pump that has been shown to mediate endothelium-dependent relaxation of vascular smooth muscle, is also expressed in tracheal epithelium [9].
• ATP also elicited an epithelium-dependent relaxation similar to SP but with a more rapid relaxation in the SERCA3(-) trachea than in the wild-type trachea [9].

Other interactions of Atp2a3

• Furthermore, immuno-electron microscopy studies confirm that IRS-1 and SERCA3b localize to vesicles derived from the ER [1].
• Sarco(endo)plasmic reticulum Ca2+ ATPase isoform 3 (SERCA3) is one of two Ca2+ pumps serving intracellular Ca2+ signaling pools in non-muscle tissues; however, unlike the ubiquitous SERCA2b, it exhibits a restricted cell-type distribution [10].
• Immunocytochemistry showed that SERCA3 is restricted to beta-cells in the mouse pancreas [4].

Analytical, diagnostic and therapeutic context of Atp2a3

• Gene targeting was used to generate a mouse with a null mutation in the SERCA3 gene [10].
• We then isolated and sequenced the 3' end portion of the mouse SERCA 3 gene, and confirmed the presence of an alternative mRNA transcript by sequencing a cDNA fragment obtained by RT-PCR [5].
• Resting [Ca(2+)](ER) (approximately 250 micromol/l) was markedly reduced after suppression (by approximately 40%) of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)-2b but not the SERCA3 isoform by microinjection of antisense oligonucleotides, implicating SERCA2b as the principle ER Ca(2+)-ATPase in this cell type [11].

References