PXD017011

PXD017011 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biomedical

submitter keyword: Pendred syndrome, EphA2, ephrin-B2

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

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PRIDE project URI

• PRIDE
  1. PXD017011
     1. Label: PRIDE project
     2. Name: Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome