ArticleThe Biochemical journal2003
Human recombinant endopeptidase PHEX has a strict S1' specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 98 citations in OpenAlex.
- Identification of a Novel Missense Mutation of theFrontiers in genetics · 2022Article
- Alkaline Phosphatase Replacement Therapy for Hypophosphatasia in Development and Practice.Advances in experimental medicine and biology · 2019Review
- Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy.Drug design, development and therapy · 2018Review
- Excessive Osteocytic Fgf23 Secretion Contributes to Pyrophosphate Accumulation and Mineralization Defect in Hyp Mice.PLoS biology · 2016Article
- Article
- PHEX mimetic (SPR4-peptide) corrects and improves HYP and wild type mice energy-metabolism.PloS one · 2014Article
- The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled.Cell biochemistry and function · 2012Review
- Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.Critical reviews in eukaryotic gene expression · 2012Review
- Evidence for FGF23 involvement in a bone-kidney axis regulating bone mineralization and systemic phosphate and vitamin D homeostasis.Advances in experimental medicine and biology · 2012Review
- Regulation and function of the FGF23/klotho endocrine pathways.Physiological reviews · 2012Review
- Proteomic analyses reveal an acidic prime side specificity for the astacin metalloprotease family reflected by physiological substrates.Molecular & cellular proteomics : MCP · 2011Article
- ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate.American journal of physiology. Renal physiology · 2011Article
- Abnormal presence of the matrix extracellular phosphoglycoprotein-derived acidic serine- and aspartate-rich motif peptide in human hypophosphatemic dentin.The American journal of pathology · 2010Article
- Expression and distribution of SIBLING proteins in the predentin/dentin and mandible of hyp mice.Oral diseases · 2010Article
- Novel regulators of Fgf23 expression and mineralization in Hyp bone.Molecular endocrinology (Baltimore, Md.) · 2009Article
- Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator.Endocrinology · 2009Article
- Studies of the DMP1 57-kDa functional domain both in vivo and in vitro.Cells, tissues, organs · 2009Article
- Phosphate: known and potential roles during development and regeneration of teeth and supporting structures.Birth defects research. Part C, Embryo today : reviews · 2008Review
- Endocrine functions of bone in mineral metabolism regulation.The Journal of clinical investigation · 2008Review
- Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP.Endocrinology · 2008Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) encodes a protein (PHEX) with structural homologies to members of the M13 family of zinc metallo-endopeptidases. Mutations in the PHEX gene are responsible for X-linked hypophosphataemia in humans. However, the mechanism by which loss of PHEX function results in the disease phenotype, and the endogenous PHEX substrate(s) remain unknown. In order to study PHEX substrate specificity, combinatorial fluorescent-quenched peptide libraries containing o -aminobenzoic acid (Abz) and 2,4-dinitrophenyl (Dnp) as the donor-acceptor pair were synthesized and tested as PHEX substrates. PHEX showed a strict requirement for acidic amino acid residues (aspartate or glutamate) in S(1)' subsite, with a strong preference for aspartate. Subsites S(2)', S(1) and S(2) exhibited less defined specificity requirements, but the presence of leucine, proline or glycine in P(2)', or valine, isoleucine or histidine in P(1) precluded hydrolysis of the substrate by the enzyme. The peptide Abz-GFSDYK(Dnp)-OH, which contains the most favourable residues in the P(2) to P(2)' positions, was hydrolysed by PHEX at the N-terminus of aspartate with a k(cat)/ K(m) of 167 mM(-1) x s(-1). In addition, using quenched fluorescence peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein sequences flanked by Abz and N -(2,4-dinitrophenyl)ethylenediamine, we showed that these physiologically relevant proteins are potential PHEX substrates. Finally, our results clearly indicate that PHEX does not have neprilysin-like substrate specificity.
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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.