PXD028021

PXD028021 is an original dataset announced via ProteomeXchange.

Title	Identification of cardiac ion channel protein networks and their signature in the human electrocardiogram
Description	Protein-protein interactions are essential for normal cellular processes and signaling events. Defining these interaction networks is therefore crucial for understanding complex cellular functions and interpretation of disease-associated gene variants. We need to build a comprehensive picture of the interactions, their affinities and interdependencies in the specific organ and cell-type to understand hitherto poorly understood signaling mechanism through ion channels and to begin their mechanistic studies. Here, we experimentally identify the ensemble of interacting partners for 13 types of ion channel in murine cardiac tissue to understand their role in cardiomyocyte electrophysiology. Of these, we validated the functional importance of 10 novel interactors on cardiac electrophysiology through genetic knockouts in zebrafish, super resolution microscopy, and patch clamp experiments. Furthermore, we establish a computational framework to reconstruct human cardiomyocyte ion channel networks from deep proteome mapping of human heart tissue and human heart single-cell gene-expression data. Finally, we integrate the ion channel interactome with human population genetics data to identify proteins that influence the electrocardiogram (ECG). The combined channel network is enriched for proteins influencing the ECG; with 44% of the network proteins significantly associated with an ECG phenotype. Altogether, we comprehensively define the interactomes of 13 major cardiac ion channels, contextualize their relevance to human electrophysiology including impact on the ECG, and validate the functional roles of ten novel interactors, thereby creating a roadmap for our understanding of how ion channel interactomes regulate cardiac electrophysiology.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:22.794.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Svetlana Maurya
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-18 23:35:28	ID requested
1	2023-09-18 16:22:32	announced
⏵ 2	2023-11-14 08:57:23	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: LC-MS, Cardiac ion channels, mouse, Interactomics, electrocardiogram

Alicia Lundby
contact affiliation	Department of Biomedical Sciences, Affiliated with The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen.
contact email	alicia.lundby@sund.ku.dk
lab head
Svetlana Maurya
contact affiliation	University of Copenhagen, Denmark University of California, San Diego
contact email	svetlana.maurya@sund.ku.dk
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/2023/09/PXD028021

PRIDE project URI

• PRIDE
  1. PXD028021
     1. Label: PRIDE project
     2. Name: Identification of cardiac ion channel protein networks and their signature in the human electrocardiogram