PXD011841

PXD011841 is an original dataset announced via ProteomeXchange.

Title	Identification of P4-ATPase Phospholipid Flippases in Red Blood Cells and Functional Analysis of Disease-associated Mutants
Description	ATP-dependent phospholipid flippase activity crucial for generating lipid asymmetry in membranes was first detected in red blood cells (RBCs), but the P4-ATPases responsible have not been directly determined. Using affinity-based mass spectrometry, we show that ATP11C is the only abundant P4-ATPase in human RBCs, while ATP11C and ATP8A1 are the major P4-ATPases in mouse RBCs. ATP11A and ATP11B are detectable at low levels. Mutations in ATP11C are responsible for blood and liver disorders, but the mechanisms are not known. Using heterologous expression, we show that the T418N mutation localized in the conserved phosphorylation motif of ATP11C and responsible for human congenial hemolytic anemia expresses at low levels, is retained in the endoplasmic reticulum, and has 33% of wild-type ATP11C activity. The I355K mutant in the transmembrane domain associated with cholestasis and anemia in mice expresses at wild-type levels and traffics to the plasma membrane, but is devoid of activity. We conclude that the T418N mutation of ATP11C causes significant protein misfolding, whereas the I355K mutant folds normally, but lacks key contacts required for functional activity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:50:57.909.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jenny Moon
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-27 02:20:45	ID requested
1	2019-03-08 00:55:08	announced
⏵ 2	2024-10-22 04:50:58	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: LC-MS/MS, P4-ATPases, Affinity chromatography, Phospholipid flippases, Red Blood Cells, Disesaes-associated Mutations

Robert S. Molday
contact affiliation	Biochemistry and Molecular Biology, University of British Columbia, Canada
contact email	molday@mail.ubc.ca
lab head
Jenny Moon
contact affiliation	University of British Columbia
contact email	kyungmee@mail.ubc.ca
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/2019/03/PXD011841

PRIDE project URI

• PRIDE
  1. PXD011841
     1. Label: PRIDE project
     2. Name: Identification of P4-ATPase Phospholipid Flippases in Red Blood Cells and Functional Analysis of Disease-associated Mutants