PXD037101 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Amino Acids Downregulate SIRT4 to Detoxify Ammonia through the Urea Cycle |
Description | Ammonia 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:58:21.628.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Songhua Hu |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | carbamoylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-30 04:01:30 | ID requested | |
1 | 2023-03-29 08:24:28 | announced | |
⏵ 2 | 2023-11-14 08:58:22 | announced | 2023-11-14: 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 affiliation | The Obstetrics & Gynecology Hospital of Fudan University, Shanghai, china |
contact email | zhaosm@fudan.edu.cn |
lab head | |
Songhua Hu |
contact affiliation | Fudan University |
contact email | h_songhua@126.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD037101
- Label: PRIDE project
- Name: Amino Acids Downregulate SIRT4 to Detoxify Ammonia through the Urea Cycle