PXD048010-1

PXD048010 is an original dataset announced via ProteomeXchange.

Title	ABCC4 protein interactions using IP-MS/MS
Description	The ATP-binding cassette transporter ABCC4 regulates cAMP membrane microdomain formation after adenylate cyclase activation but how ABCC4 localizes to these membrane microdomains are still unclear. Herein we demonstrate that the assembly and spatiotemporal organization of ABCC4’s protein neighborhood by PKA requires its PDZ motif and PKA activation. Density gradient ultracentrifugation revealed the formation of ABCC4 PDZ motif–specific, large protein complex upon PKA activation. To elucidate how PKA ushers ABCC4 to form this membrane supercomplex we identified proteins that closely interact with ABCC4 and proteins in ABCC4’s “neighborhood” network using Avi-tagged or APEX-tagged ABCC4 constructs, and their deletion mutants without the PDZ motif. We found that ABCC4 interacts with numerous PDZ domain containing proteins (PDZ proteins), and the PKA-induced enrichment of actin filament-binding proteins in the vicinity of ABCC4 requires the PDZ motif. The assembly of the supercomplex was crucially dependent on the actin-binding protein Moesin (MSN), which also interacts with the PDZ motif. This supercomplex can be disrupted by a specific potent inhibitor of ABCC4. These findings indicate that PKA activation promotes ABCC4 membrane localization by enhancing the assembly of a protein scaffold through PDZ proteins, MSN and actin cytoskeletal proteins.
HostingRepository	PRIDE
AnnounceDate	2025-09-09
AnnouncementXML	Submission_2025-09-09_08:22:19.361.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andy High
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-20 10:37:29	ID requested
⏵ 1	2025-09-09 08:22:19	announced

Dataset with its publication pending

submitter keyword: ABBC4, MS/MS, PDZ motif, IP

John Schuetz
contact affiliation	Member, Pharmacy $ Pharmaceutical Sciences, St Jude Children's Research Hospital
contact email	john.schuetz@stjude.org
lab head
Andy High
contact affiliation	St Jude Children's Reserach Hospital
contact email	anthony.high@stjude.org
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/2025/09/PXD048010

PRIDE project URI

• PRIDE
  1. PXD048010
     1. Label: PRIDE project
     2. Name: ABCC4 protein interactions using IP-MS/MS