InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: KL

Summary

InnateDB Protein

IDBP-23285.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Protein Name

klotho

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000369442

InnateDB Gene

IDBG-23283 (KL)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.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. {ECO:0000250}.

Subcellular Localization

Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Isoform 1 shedding leads to a soluble peptide.Isoform 2: Secreted.Klotho peptide: Secreted.

Disease Associations

Tumoral calcinosis, hyperphosphatemic, familial (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. {ECO:0000269PubMed:17710231}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:10631108, ECO:0000269PubMed:11043382, ECO:0000269PubMed:11162628, ECO:0000269PubMed:15135068, ECO:0000269PubMed:9464267}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds
GO:0004566	beta-glucuronidase activity
GO:0004871	signal transducer activity
GO:0005104	fibroblast growth factor receptor binding
GO:0005179	hormone activity
GO:0005499	vitamin D binding
GO:0005515	protein binding
GO:0008422	beta-glucosidase activity
GO:0017134	fibroblast growth factor binding

Biological Process

GO:0002526	acute inflammatory response
GO:0005975	carbohydrate metabolic process
GO:0006112	energy reserve metabolic process
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007568	aging
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0030501	positive regulation of bone mineralization
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0045087	innate immune response
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0055074	calcium ion homeostasis
GO:0090080	positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane
GO:0070062	extracellular vesicular exosome