PXD004518-1

PXD004518 is an original dataset announced via ProteomeXchange.

Title	Redirected nuclear glutamate dehydrogenase supplies Tet3 with a-ketoglutarate in neurons
Description	Tet3 is an Fe2+-dependent enzyme that oxidizes genomic 5-methylcytosine to 5-hydroxymethylcytosine with the help of alpha-ketoglutarate and oxygen. It is the most abundant Tet enzyme in differentiated tissues including brain. Adult brain contains the highest 5-hydroxymethylcytosine levels. How alpha-ketoglutarate is made available for the oxidation of mC in brain cells and how the Tet activity is linked to neural activity are unsolved questions. Our experiments with full mouse brains show that Tet3 interacts in the nucleus directly with selected enzymes of the mitochondrial citric acid cycle. This leads to the formation of isocitrate. Tet3 also interacts with aspartate aminotransferase, which produces oxaloacetate. Although oxaloacetate and isocitrate are biosynthetic alpha-ketoglutarate precursors, they function as inhibitors of Tet3 and are needed to protect the reactive Fe2+ center from degrading DNA. The supply of Tet3 with alpha-ketoglutarate is established by a direct interaction of Tet3 with glutamate dehydrogenase (Glud1), which converts the neurotransmitter glutamate directly into alpha-ketoglutarate. This links Tet3 function to neural activity.
HostingRepository	PRIDE
AnnounceDate	2021-05-10
AnnouncementXML	Submission_2021-05-09_23:07:29.434.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Künzel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-07-05 07:36:56	ID requested
⏵ 1	2021-05-09 23:07:29	announced
2	2021-07-20 02:51:02	announced	2021-07-20: Updated publication reference for PubMed record(s): 34215750.
3	2024-10-22 05:21:57	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: citric acid cycle, epigenetics, alpha-ketoglutarate, oxaloacetate,Tet3, isocitrate, hmC

Thomas Carell
contact affiliation	Faculty of Chemistry and Pharmacy, Ludwig-Maximilians-Universität München, Germany
contact email	thomas.carell@lmu.de
lab head
Andrea Künzel
contact affiliation	LMU
contact email	andrea.kuenzel@cup.lmu.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004518
     1. Label: PRIDE project
     2. Name: Redirected nuclear glutamate dehydrogenase supplies Tet3 with a-ketoglutarate in neurons