PXD013053

PXD013053 is an original dataset announced via ProteomeXchange.

Title	Discovery of DYRK1A dependent phosphorylation in mouse embryonic heart
Description	The Dp1Tyb mouse model for Down syndrome contains a duplication of 23Mb of mouse chromosome 16 (Mmu16) that is orthologous to human chromosome 21 (Hsa21). This region contains 145 coding genes, and thus these genes are present in 3 copies. Dp1Tyb mice display congenital heart defects, similar to the ones seen in people with Down syndrome. These defects include ventricular and atrio-ventricular septal defects and are seen at embryonic day 14.5 (E14.5) of gestation. One of the 145 genes present in 3 copies in Dp1Tyb mice codes for a kinase called DYRK1A. We found that by crossing Dp1Tyb mice with mice carrying a heterozygous Dyrk1a loss of function allele, thereby reducing the dosage of the Dyrk1a gene from 3 to 2 copies, we rescue the congenital heart defects. Thus 3 copies of Dyrk1a are required to cause heart defects, and, presumably, increased DYRK1A protein is required for the heart defects. We compared the phosphoproteome in Dp1Tyb versus Dp1TybDyrk1a+/+/- embryonic hearts in order to discover alterations in phosphoproteins that could pinpoint molecular mechanisms that give rise to the congenital heart defects. The two strains (Dp1Tyb and Dp1TybDyrk1a+/+/-) differ only in the copy number of Dyrk1a (3 v 2) and thus differences in phosphoproteins would include both direct and indirect targets of DYRK1A activity.
HostingRepository	PRIDE
AnnounceDate	2024-02-13
AnnouncementXML	Submission_2024-02-13_13:57:38.816.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Helen Flynn
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-12 02:48:42	ID requested
1	2024-02-01 06:20:26	announced
2	2024-02-07 03:35:47	announced	2024-02-07: Updated project metadata.
⏵ 3	2024-02-13 13:57:39	announced	2024-02-13: Updated project metadata.

10.1126/SCITRANSLMED.ADD6883;

curator keyword: Biological

submitter keyword: IMAC, Orbitrap Fusion Lumos,TiO2, LC-MS/MS

Ambrosius P.
contact affiliation	Head of the Crick Mass Spectrometry Proteomics Platform
contact email	Bram.Snijders@crick.ac.uk
lab head
Helen Flynn
contact affiliation	The Francis Crick Institute
contact email	helen.flynn@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013053
     1. Label: PRIDE project
     2. Name: Discovery of DYRK1A dependent phosphorylation in mouse embryonic heart