ArticleProceedings of the National Academy of Sciences of the United States of America2014
Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
185 citing papers in PubMed, 333 citations in OpenAlex.
- Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism.The Journal of clinical endocrinology and metabolism · 2015Trial
- Phosphate homeostasis and endocrine regulators.Pediatric nephrology (Berlin, Germany) · 2026Review
- BoneJBMR plus · 2026Article
- When X Does Not Mark the Spot: Autosomal Dominant and Recessive Forms of Renal Hypophosphatemic Rickets and Osteomalacia.Current osteoporosis reports · 2026Review
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- Hypophosphatemic rickets: diagnosis and treatment.Archives of endocrinology and metabolism · 2026Review
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- Iron-Induced Hypophosphatemia: A Review of Pathophysiology, Drug Safety, and Pharmacogenomic Perspectives.Journal of hematology · 2025Review
- A centenarian single nucleotide polymorphism in collagen gene COL25A1 promotes longevity in C. elegans.npj aging · 2025Article
- Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.Journal of human genetics · 2025Review
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- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- The Roxadustat (FG-4592) ameliorates tubulointerstitial fibrosis by promoting intact FGF23 cleavage.Cell communication and signaling : CCS · 2025Article
- Review
- Maternal excess dietary phosphate intake in the periconceptional period is a potential risk for mineral disorders in offspring mice.Scientific reports · 2025Article
- iFGF23 Plasma Levels in Transfusion-Dependent β-Thalassemia: Insights into Bone and Iron Metabolism.Journal of clinical medicine · 2025Article
- C-terminal FGF-23 production coupling with aldosterone via FAM20C and predicting cardiovascular events in primary aldosteronism.JCI insight · 2025Article
- A transgenic mouse line with a 58 kb fragment deletion shows skeletal defects.Scientific reports · 2025Article
- Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome.BMC molecular and cell biology · 2025Article
- Emerging concepts on the FGF23 regulation and activity.Molecular and cellular biochemistry · 2025Review
125 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
The family with sequence similarity 20, member C (Fam20C) has recently been identified as the Golgi casein kinase. Fam20C phosphorylates secreted proteins on Ser-x-Glu/pSer motifs and loss-of-function mutations in the kinase cause Raine syndrome, an often-fatal osteosclerotic bone dysplasia. Fam20C is potentially an upstream regulator of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23), because humans with FAM20C mutations and Fam20C KO mice develop hypophosphatemia due to an increase in full-length, biologically active FGF23. However, the mechanism by which Fam20C regulates FGF23 is unknown. Here we show that Fam20C directly phosphorylates FGF23 on Ser(180), within the FGF23 R(176)XXR(179)/S(180)AE subtilisin-like proprotein convertase motif. This phosphorylation event inhibits O-glycosylation of FGF23 by polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-T3), and promotes FGF23 cleavage and inactivation by the subtilisin-like proprotein convertase furin. Collectively, our results provide a molecular mechanism by which FGF23 is dynamically regulated by phosphorylation, glycosylation, and proteolysis. Furthermore, our findings suggest that cross-talk between phosphorylation and O-glycosylation of proteins in the secretory pathway may be an important mechanism by which secreted proteins are regulated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.