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PXD037101

PXD037101 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAmino Acids Downregulate SIRT4 to Detoxify Ammonia through the Urea Cycle
DescriptionAmmonia production via glutamate dehydrogenase is inhibited by SIRT4, a sirtuin that displays both amidase and non-amidase activities. The processes underlying the regulation of ammonia removal by amino acids remain unclear. Here, we report that SIRT4 acts as a decarbamylase that responds to amino acid sufficiency and regulates ammonia removal. Amino acids promote lysine 307 carbamylation (OTCCP-K307) of ornithine transcarbamylase (OTC), which activates OTC and the urea cycle. Proteomic and interactome screening identified OTC as a substrate of SIRT4. SIRT4 decarbamylates OTCCP-K307 and inactivates OTC in a NAD+-dependent manner. SIRT4 expression was transcriptionally upregulated by the amino acid insufficiency-activated GCN2–eIF2a–ATF4 axis. SIRT4 knockout in cultured cells caused higher OTCCP-K307 levels, activated OTC, elevated urea cycle intermediates, and urea production via amino acid catabolism. Sirt4 ablation decreased mouse blood ammonia levels and ameliorated CCl4-induced hepatic encephalopathy phenotypes. We reveal that SIRT4 safeguards cellular ammonia toxicity during amino acid catabolism.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:58:21.628.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSonghua Hu
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListcarbamoylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-30 04:01:30ID requested
12023-03-29 08:24:28announced
22023-11-14 08:58:22announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Liver (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project
submitter keyword: carbamylation,liver,Mice
Contact List
Shimin Zhao
contact affiliationThe Obstetrics & Gynecology Hospital of Fudan University, Shanghai, china
contact emailzhaosm@fudan.edu.cn
lab head
Songhua Hu
contact affiliationFudan University
contact emailh_songhua@126.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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