Disintegrin-and-metalloproteinase-19 cleaves parathyroid hormone receptor and could cause brachydactyly type E

ABSTRACT: Brachydactyly type E (BDE), shortened metacarpals, metatarsals, cone-shaped epiphyses, and short stature, is an autosomal-dominant condition that commonly occurs as a sole phenotype. Parathyroid hormone-like protein (PTHrP) has been shown to be responsible in all forms to date, either directly or indirectly. We used linkage and then whole genome sequencing in a small pedigree, to elucidate BDE and identified a truncated disintegrin-and-metalloproteinase-19 (ADAM19) allele in all affected family members, but not in nonaffected persons. Since we had shown earlier that the extracellular domain of the parathyroid hormone receptor (PTHR1) is subject to an unidentified metalloproteinase cleavage, we tested the hypothesis that ADAM19 is a sheddase for PTHR1. Wild-type ADAM19 cleaved PTHR1, while mutated ADAM-19 did not. Alanine substitutions mapped the N-terminal cleavage site of PTHR1. For mass spectrometry verification, different proteases have been used, to identify the cleavage products in ADAM-19 and PTHR1 transfected HEK-293 cells.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Henrik Zauber  

LAB HEAD: Matthias Selbach

PROVIDER: PXD044793 | Pride | 2026-07-07

REPOSITORIES: Pride