Klotho (KL) Human Active Protein

Klotho: 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. Essential factor for the specific interaction between FGF23 and FGFR1. Defects in KL are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC). A severe metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients manifest recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement. Belongs to the glycosyl hydrolase 1 family. Klotho subfamily. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: EC 3.2.1.31; Membrane protein, integral; Hydrolase

Chromosomal Location of Human Ortholog: 13q12

Cellular Component: extracellular space; integral to plasma membrane; plasma membrane; extracellular region; integral to membrane

Molecular Function: vitamin D binding; signal transducer activity; beta-glucosidase activity; beta-glucuronidase activity; fibroblast growth factor binding; hormone activity; fibroblast growth factor receptor binding

Biological Process: calcium ion homeostasis; epidermal growth factor receptor signaling pathway; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; nerve growth factor receptor signaling pathway; carbohydrate metabolic process; energy reserve metabolic process; insulin receptor signaling pathway; innate immune response; positive regulation of bone mineralization; acute inflammatory response; aging

Disease: Tumoral Calcinosis, Hyperphosphatemic, Familial