PXD017011 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome |
Description | Enlarged vestibular aqueducts (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:02:20.312.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Scientific Service Group Biomolecular Mass Spectrometry |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-01-08 05:49:09 | ID requested | |
1 | 2020-01-16 06:55:41 | announced | |
⏵ 2 | 2024-10-22 05:02:21 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1038/s41467-020-15198-9; |
Li M, Nishio SY, Naruse C, Riddell M, Sapski S, Katsuno T, Hikita T, Mizapourshafiyi F, Smith FM, Cooper LT, Lee MG, Asano M, Boettger T, Krueger M, Wietelmann A, Graumann J, Day BW, Boyd AW, Offermanns S, Kitajiri SI, Usami SI, Nakayama M, Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome. Nat Commun, 11(1):1343(2020) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Pendred syndrome, EphA2, ephrin-B2 |
Contact List
Masanori Nakayama |
contact affiliation | Max Planck Institute for Heart and Lung Research, Laboratory for Cell Polarity and Organogenesis, Germany |
contact email | masanori.nakayama@mpi-bn.mpg.de |
lab head | |
Scientific Service Group Biomolecular Mass Spectrometry |
contact affiliation | Max Planck Institute for Heart and Lung Research |
contact email | proteomics@mpi-bn.mpg.de |
dataset submitter | |
Full Dataset Link List
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/2020/04/PXD017011 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017011
- Label: PRIDE project
- Name: Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome