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. 2021 Mar 11;12:636403. doi: 10.3389/fendo.2021.636403

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Copyright © 2021 Devesa

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Klotho cleavage mechanisms. Klotho cleavage occurs in the extracellular domain of the klotho protein and is carried out by proteases (ADAM10 and ADAM17). In kidney cells, cleavage at a site directly above the cell membrane (α-cut) results in full-length circulating soluble klotho, which can act in many different organs and tissues. The other type of cleavage (ß-cut) occurs between the KL1 and KL2 domains that give rise to the KL2 and KL1 fragments. TM, membrane portion of klotho. CYT, intracellular portion of klotho.