ArticleThe Biochemical journal2001
Characterization of PHEX endopeptidase catalytic activity: identification of parathyroid-hormone-related peptide107-139 as a substrate and osteocalcin, PPi and phosphate as inhibitors.
Article in The Biochemical journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 81 citations in OpenAlex.
- Treatment with Minicircle DNA Expressing a FGF23 Fragment in a Clinically relevant Mouse Model of X-Linked Hypophosphatemic Rickets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Characterization of Novel PHEX Variants in X-linked Hypophosphatemic Rickets and Genotype-PHEX Activity Correlation.The Journal of clinical endocrinology and metabolism · 2024Article
- Function of PHEX mutations p.Glu145* and p.Trp749Arg in families with X-linked hypophosphatemic rickets by the negative regulation mechanism on FGF23 promoter transcription.Cell death & disease · 2022Article
- PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond.Frontiers in endocrinology · 2022Review
- Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration.Translational research : the journal of laboratory and clinical medicine · 2020Article
- Proteolytic Regulation of Parathyroid Hormone-Related Protein: Functional Implications for Skeletal Malignancy.International journal of molecular sciences · 2019Review
- 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
- Review
- Expression and distribution of SIBLING proteins in the predentin/dentin and mandible of hyp mice.Oral diseases · 2010Article
- Dentin noncollagenous matrix proteins in familial hypophosphatemic rickets.Cells, tissues, organs · 2009Article
- Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP.Endocrinology · 2008Article
- DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.Nature genetics · 2006Article
- Article
- The wrickkened pathways of FGF23, MEPE and PHEX.Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists · 2004Review
- Article
- 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.The Biochemical journal · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) are responsible for X-linked hypophosphataemia, and studies in the Hyp mouse model of the human disease implicate the gene product in the regulation of renal phosphate (P(i)) reabsorption and bone mineralization. Although the mechanism for PHEX action is unknown, structural homologies with members of the M13 family of endopeptidases suggest a function for PHEX protein in the activation or degradation of peptide factors involved in the control of renal P(i) transport and matrix mineralization. To determine whether PHEX has endopeptidase activity, we generated a recombinant soluble, secreted form of human PHEX (secPHEX) and tested the activity of the purified protein with several peptide substrates, including a variety of bone-related peptides. We found that parathyroid-hormone-related peptide(107-139) is a substrate for secPHEX and that the enzyme cleaves at three positions within the peptide, all located at the N-terminus of aspartate residues. Furthermore, we show that osteocalcin, PP(i) and P(i), all of which are abundant in bone, are inhibitors of secPHEX activity. Inhibition of secPHEX activity by osteocalcin was abolished in the presence of Ca(2+). We suggest that PHEX activity and mineralization may be controlled in vivo by PP(i)/P(i) and Ca(2+) and, in the latter case, the regulation requires the participation of osteocalcin.
Indexed as
Identifiers
What OpenQuestion holds
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.