Phosphate-regulating neutral endopeptidase PHEX

Definition:

Peptidase that cleaves SIBLING (small integrin-binding ligand, N-linked glycoprotein)-derived ASARM peptides, thus regulating their biological activity. Cleaves ASARM peptides between Ser and Glu or Asp residues. Regulates osteogenic cell differentiation and bone mineralization through the cleavage of the MEPE-derived ASARM peptide. Promotes dentin mineralization and renal phosphate reabsorption by cleaving DMP1- and MEPE-derived ASARM peptides. Inhibits the cleavage of MEPE by CTSB/cathepsin B thus preventing MEPE degradation.

References:

[1]. Rong Guo, et al. Inhibition of MEPE cleavage by Phex. Biochem Biophys Res Commun. 2002 Sep 13;297(1):38-45. [Content Brief]

[2]. M L Lipman, et al. Cloning of human PEX cDNA. Expression, subcellular localization, and endopeptidase activity. J Biol Chem. 1998 May 29;273(22):13729-37. [Content Brief]

[3]. Peter S N Rowe, et al. Surface plasmon resonance (SPR) confirms that MEPE binds to PHEX via the MEPE-ASARM motif: a model for impaired mineralization in X-linked rickets (HYP). Bone. 2005 Jan;36(1):33-46. [Content Brief]

[4]. William N Addison, et al. MEPE-ASARM peptides control extracellular matrix mineralization by binding to hydroxyapatite: an inhibition regulated by PHEX cleavage of ASARM. J Bone Miner Res. 2008 Oct;23(10):1638-49. [Content Brief]

[5]. Aline Martin, et al. Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP. Endocrinology. 2008 Apr;149(4):1757-72. [Content Brief]

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