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CHP2 (calcineurin B homologous protein 2), also known as hepatocellular carcinoma-associated antigen 520, is a 196 amino acid protein that contains 4 EF-hand domains and plays a potential role in transmembrane Na+/H+ exchange. By binding to and activating NHE-1, CHP2 increases the pH and works to protect cells from serum deprivation-induced death. Though not typically detected in normal tissues, CHP2 is highly expressed in malignantly transformed cells and is therefore considered to be a tumor-associated antigen. Ectopic expression of CHP2 promotes proliferation of HEK293 cells and knockdown of CHP2 mRNA in HepG2 cells inhibits cell proliferation. Like calcineurin B, CHP2 can bind to and stimulate phosphatase activity of calcineurin A and activate the calcineurin/NFAT signaling pathway.
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