| A 20-aa peptide sequence near the cytoplasmic C-terminus of rat CaT-2/ECAC1 . Calcium (Ca+2 or Ca) is the most abundant cation and it is required for many physiological activities such as bone formation and it acts as a second messenger in signal transduction. However only 1% of Ca is present in ionic form in biological fluids. Ca concentration is regulated by calcitropic hormones that act on bone, kidney, and intestine. Extracellular Ca+-levels are sensed and regulated by Calcium Sensing receptor (CASR). When Ca levels are limiting then it must be taken up by active, transcellular pathways comprising (1) Ca++ entry across apical membrane, (2) cytosolic transport of Ca++ across the cell form apical to basolateral membrane facilitated by a family of low mol wt Calcium binding proteins (CABPs) that include vitamin D3-dependent Ca++ binding proteins (calbindin-D9k, Calbindin-28k, Calretinin, Parvalbumin, S100, calmodulin) and finally (3) an active extrusion of Ca++ through basolateral membrane mediated by Ca++-ATPase and Na+-Ca++ exchangers (NCX). Ca++ absorption in intestine and its reabsorption in kidney are carried out by Ca++ Transport (CaT) proteins, CaT-1, CaT-2 or Epithelial Ca Channel (ECAC1/ECAC2/CaT-Like (CaT-L) proteins. CaT2 (rat 723 aa, human 729 aa, chromosome 7q35) is also known as ECAC1 or TRPV5) is ~75% homologous with CAT1. In contrast to CaT-1, CaT-2 is exclusively expressed in kidney and absent in intestine, brain, heart, liver, lung, skeletal muscle, spleen, thymus, testis, adrenal gland. It colocalizes with calbindin D28K and Na+ channel exchanger 1 (NCX1). CaT-2 mediates saturable apical Ca++ uptake by the cells of distal convoluted tubule and connecting segment of nephron where active re-absorption of Ca++ takes place via transcellular route. CaT-2 has moderate abilities to transport Sr++ and Ba++. A strong inhibition of CaT-2 mediated Ca++ transport by Cd++ leads to hypercalciurea and renal stone formation. |
