PXD035535-1

PXD035535 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics of cardiac organoids derived from ALPK3 knockout hPSCs
Description	Pathogenic mutations in alpha kinase 3 (ALPK3) cause cardiomyopathy and a range of musculoskeletal defects. How ALPK3 mutations result in disease remains unclear and little is known about this atypical kinase. Using a suite of engineered human pluripotent stem cells (hPSCs) we show that ALPK3 localizes to the sarcomere, specifically at the M-Band. Both sarcomeric organization and calcium kinetics were disrupted in ALPK3 deficient hPSC derived cardiomyocytes. Further, cardiac organoids derived from ALPK3 knockout hPSCs displayed reduced force generation. Phosphoproteomic profiling of wildtype and ALPK3 null hPSC derived cardiomyocytes revealed ALPK3-dependant phospho-peptides were enriched for proteins involved in sarcomere function and protein quality control. We demonstrate that ALPK3 binds to the selective autophagy receptor SQSTM1 (Sequestome 1) and is required for the sarcomeric localization of SQSTM1. We propose that ALPK3 is a myogenic kinase with an integral role in the intracellular signaling networks underlying sarcomere maintenance required for continued cardiac contractility.
HostingRepository	PRIDE
AnnounceDate	2023-01-19
AnnouncementXML	Submission_2023-01-18_22:29:50.108.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	BenjaminParker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-24 05:03:32	ID requested
⏵ 1	2023-01-18 22:29:50	announced
2	2024-10-22 05:41:45	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: cardiac organoids,ALPK3, phosphoproteomics

BenjaminParker
contact affiliation	The University of Melbourne
contact email	ben.parker@unimelb.edu.au
lab head
BenjaminParker
contact affiliation	The University of Melbourne
contact email	ben.parker@unimelb.edu.au
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/2023/01/PXD035535

PRIDE project URI

• PRIDE
  1. PXD035535
     1. Label: PRIDE project
     2. Name: Phosphoproteomics of cardiac organoids derived from ALPK3 knockout hPSCs