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PXD060411-1

PXD060411 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA functional map of phosphoprotein phosphatase regulation identifies an evolutionary conserved reductase for the active site
DescriptionSer/Thr phosphoprotein phosphatases (PPPs, PP1-PP7) are conserved metalloenzymes and central regulators of cellular signaling in eukaryotes, but the details of their assembly and regulation are not fully understood. To address this, we performed genome-wide CRISPR knockout and focused high resolution base editor screens to functionally interrogate PPP regulation in human cells. This uncovered several novel regulators including the poorly studied reductase CYB5R4 which we identify as an evolutionarily conserved activator of PP4 and PP6. CYB5R4 heme binding is essential for this function and mechanistically involves the reduction of the metal ions in the active site. Importantly, this function of CYB5R4 controls the cellular response to DNA damage inducing chemotherapeutic agents. In sum we provide a high resolution functional map of PPP regulation and uncover that active site metal ion redox state is an integral regulatory mechanism of PPP biology.
HostingRepositoryMassIVE
AnnounceDate2026-04-22
AnnouncementXMLSubmission_2026-04-22_02:57:30.511.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterArminja Nadine Kettenbach
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos; Orbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-02-02 09:45:29ID requested
12026-04-22 02:57:31announced
Publication List
no publication
Keyword List
submitter keyword: Phosphatase, biogenesis, PP2A-like, DatasetType:Proteomics
Contact List
Arminja Kettenbach
contact affiliationThe Geisel School of Medicine at Dartmouth
contact emailarminja.n.kettenbach@dartmouth.edu
lab head
Arminja Nadine Kettenbach
contact affiliationDartmouth
contact emailArminja.N.Kettenbach@Dartmouth.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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