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. 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. Belongs to the glycosyl hydrolase 1 family. Klotho subfamily. Present in cortical renal tubules (at protein level). Soluble peptide is present in serum and cerebrospinal fluid. Expressed in kidney, placenta, small intestine and prostate. Down-regulated in renal cell carcinomas, hepatocellular carcinomas, and in chronic renal failure kidney. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Hydrolase; Membrane protein, integral
Chromosomal Location of human Ortholog: 13q13.1
Cellular Component:  apical plasma membrane; extracellular region; plasma membrane
Molecular Function:  beta-glucosidase activity; beta-glucuronidase activity; fibroblast growth factor binding; fibroblast growth factor receptor binding; hormone activity; vitamin D binding
Biological Process:  acute inflammatory response; aging; calcium ion homeostasis; carbohydrate metabolic process; energy reserve metabolic process; fibroblast growth factor receptor signaling pathway; insulin receptor signaling pathway; negative regulation of systemic arterial blood pressure; norepinephrine biosynthetic process; positive regulation of bone mineralization; positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; response to activity; response to angiotensin; response to vitamin D
Disease: Tumoral Calcinosis, Hyperphosphatemic, Familial, 3
Reference #:  Q9UEF7 (UniProtKB)
Alt. Names/Synonyms: HFTC3; KL; KLOT; Klotho; Klotho peptide
Gene Symbols: KL
Molecular weight: 116,181 Da
Basal Isoelectric point: 8.06  Predict pI for various phosphorylation states
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene