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PXD017011

PXD017011 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDigenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome
DescriptionEnlarged 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:02:20.312.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterScientific Service Group Biomolecular Mass Spectrometry
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-01-08 05:49:09ID requested
12020-01-16 06:55:41announced
22024-10-22 05:02:21announced2024-10-22: 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 affiliationMax Planck Institute for Heart and Lung Research, Laboratory for Cell Polarity and Organogenesis, Germany
contact emailmasanori.nakayama@mpi-bn.mpg.de
lab head
Scientific Service Group Biomolecular Mass Spectrometry
contact affiliationMax Planck Institute for Heart and Lung Research
contact emailproteomics@mpi-bn.mpg.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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