May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1.
The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Database links SwissProt : Q9UEF7
1) Biochem Biophys Res Commun.2000 Jan 19;267(2):597-602.
Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys.
Kato Y, Arakawa E, Kinoshita S, Shirai A, Furuya A, Yamano K, Nakamura K, Iida A, Anazawa H, Koh N, Iwano A, Imura A, Fujimori T, Kuro-o M, Hanai N, Takeshige K, Nabeshima Y.
2) J Biol Chem. 2004 Mar 12;279(11):9777-84.
Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides.
Tohyama O, Imura A, Iwano A, Freund JN, Henrissat B, Fujimori T, Nabeshima Y.
3) FEBS Lett. 2004 May 7;565(1-3):143-7.
Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane.
Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y.
4) Science2007 Jun 15;316(5831):1615-8.
alpha-Klotho as a regulator of calcium homeostasis.
Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T, Nabeshima Y.
5) Proc Natl Acad Sci U S A2008 Mar 4;105(9):3455-60.
A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism.
Brownstein CA, Adler F, Nelson-Williams C, Iijima J, Li P, Imura A, Nabeshima Y, Reyes-Mugica M, Carpenter TO, Lifton RP.