PXD044793

PXD044793 is an original dataset announced via ProteomeXchange.

Title	Disintegrin-and-metalloproteinase-19 cleaves parathyroid hormone receptor and could cause brachydactyly type E
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-07-07
AnnouncementXML	Submission_2026-07-07_02:21:16.126.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Henrik Zauber
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 05:39:57	ID requested
⏵ 1	2026-07-07 02:21:17	announced

Aydin A, Klenk C, Nemec K, I, ş, bilir A, Martin LM, Zauber H, Rrustemi T, Toka HR, Schuster H, Gong M, Stricker S, Bock A, B, ä, hring S, Selbach M, Lohse MJ, Luft FC, ADAM19 cleaves the PTH receptor and associates with brachydactyly type E. Life Sci Alliance, 7(4):(2024) [pubmed]

10.26508/lsa.202302400;

submitter keyword: Human,Parathyroid receptor, Brachydactyly type E,Shotgun Proteomics, Disintegrin-and-metalloproteinase-19,LC-MSMS, GFP, Parathyroid-related peptide

Matthias Selbach
contact affiliation	Max Delbrück Center for Molecular Medicine in the Helmholtz Association
contact email	matthias.selbach@mdc-berlin.de
lab head
Henrik Zauber
contact affiliation	MDC Berlin-Buch
contact email	henrik.zauber@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/07/PXD044793

PRIDE project URI

• PRIDE
  1. PXD044793
     1. Label: PRIDE project
     2. Name: Disintegrin-and-metalloproteinase-19 cleaves parathyroid hormone receptor and could cause brachydactyly type E