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PXD037101-2

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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