ID:KLOT_HUMAN DESCRIPTION: RecName: Full=Klotho; EC=3.2.1.31; Contains: RecName: Full=Klotho peptide; Flags: Precursor; FUNCTION: 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 (By similarity). FUNCTION: 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 (By similarity). CATALYTIC ACTIVITY: A beta-D-glucuronoside + H(2)O = D-glucuronate + an alcohol. SUBUNIT: Homodimer (By similarity). Interacts with FGF23 and FGFR1 (By similarity). SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Isoform 1 shedding leads to a soluble peptide. SUBCELLULAR LOCATION: Isoform 2: Secreted. SUBCELLULAR LOCATION: Klotho peptide: Secreted. TISSUE SPECIFICITY: 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. DOMAIN: Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 239, and the second one lacks the essential Glu active site residue at position 872. PTM: N-glycosylated (By similarity). POLYMORPHISM: Homozygosity for KL-VS allele is associated with decreased longevity and increased cardiovascular disease risk. DISEASE: Defects in KL are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC) [MIM:211900]. 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. MISCELLANEOUS: Defects in KL may be a cause of chronic renal failure complications. SIMILARITY: Belongs to the glycosyl hydrolase 1 family. Klotho subfamily. WEB RESOURCE: Name=Protein Spotlight; Note=The thread of life - Issue 65 of December 2005; URL="http://web.expasy.org/spotlight/back_issues/sptlt065.shtml";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UEF7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
