FGF-23 Human Active Protein

This gene encodes a member of the fibroblast growth factor family of proteins, which possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. The product of this gene regulates phosphate homeostasis and transport in the kidney. The full-length, functional protein may be deactivated via cleavage into N-terminal and C-terminal chains. Mutation of this cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR). Mutations in this gene are also associated with hyperphosphatemic familial tumoral calcinosis (HFTC). [provided by RefSeq, Feb 2013]

Function: Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL

By similarity. Acts directly on the parathyroid to decrease PTH secretion

By similarity. Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization. Ref.2 Ref.8 Ref.13 Ref.14 Ref.16

Subunit structure: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL and heparan sulfate glycosaminoglycans that function as coreceptors

By similarity. Ref.14

Subcellular location: Secreted. Note: Secretion is dependent on O-glycosylation. Ref.15

Tissue specificity: Expressed in osteogenic cells particularly during phases of active bone remodeling. In adult trabecular bone, expressed in osteocytes and flattened bone-lining cells (inactive osteoblasts). Ref.11

Post-translational modification: Following secretion this protein is inactivated by cleavage into a N-terminal fragment and a C-terminal fragment. The processing is effected by proprotein convertases.O-glycosylated by GALT3. Glycosylation is necessary for secretion; it blocks processing by proprotein convertases when the O-glycan is alpha 2,6-sialylated. Competition between proprotein convertase cleavage and block of cleavage by O-glycosylation determines the level of secreted active FGF23. Ref.15

Involvement in disease: Hypophosphatemic rickets, autosomal dominant (ADHR) [MIM:193100]: A disease characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.8 Ref.15Tumoral 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Sequence similarities: Belongs to the heparin-binding growth factors family.