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PXD019886-2

PXD019886 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMETTL21C methylates Alanine tRNA synthetase at lysine 943 in muscle tissue
DescriptionProtein lysine methylation is a common post-translational modification (PTM) detected throughout the human proteome that plays important roles in diverse biological processes. In the human genome, there are greater than one hundred known and candidate protein lysine methyltransferases (PKMTs), many with important links to human disease. METTL21C (methyltransferase-like protein 21C) is a PKMT implicated in muscle biology and reported to methylate VCP (valosin-containing protein/p97) and HSPA8 (heat shock 70kDa protein 8). However, a clear in vitro methyltransferase activity for METTL21C is yet to be demonstrated. Thus, whether METTL21C is indeed an active enzyme that directly methylates substrate/s is unclear. Here, we use an unbiased biochemical-based screening assay coupled to mass spectrometry to identify Alanine-tRNA-Synthetase 1 (AARS1) as a direct substrate of METTL21C. METTL21C catalyzes mono-, di- and tri-methylation of lysine 943 of AARS1 (AARS1-K943me) in vitro and in vivo. In vitro methylation of AARS1 by METTL21C is independent of ATP or tRNA molecules. In contrast to AARS1, and in conflict with previous reports, we do not detect METTL21C methylation activity on VCP and HSPA8. Depletion of METTL21C in METTL21C-expressing cells leads to depletion of AARS1-K943 methylation. Finally, METTL2C is almost exclusively expressed in muscle tissue, and accordingly we detect the METTL21C-catalyzed methylation event of AARS1 in mouse skeletal muscle tissue. Together, our work identifies AARS1 as a bona fide substrate of METTL21C and suggests a role for the METTL21C-AARS1 axis in the regulation of protein synthesis in muscle tissue. In addition, our study describes a straightforward protocol for elucidating physiologic substrates of little characterized or uncharacterized PKMTs
HostingRepositoryPRIDE
AnnounceDate2020-07-02
AnnouncementXMLSubmission_2020-07-07_06:38:14.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMohamad Zoabi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonomethylated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-19 01:17:21ID requested
12020-07-01 21:55:17announced
22020-07-07 06:38:15announced2020-07-07: Updated publication reference for PubMed record(s): 32611769.
32024-10-22 05:08:16announced2024-10-22: Updated project metadata.
Publication List
Zoabi M, Zhang L, Li TM, Elias JE, Carlson SM, Gozani O, Methyltransferase-like 21C (METTL21C) methylates alanine tRNA synthetase at Lys-943 in muscle tissue. J Biol Chem, 295(33):11822-11832(2020) [pubmed]
Keyword List
submitter keyword: Human, LC-MS/MS, AARS1, Methylation
Contact List
Or Gozani
contact affiliationBiology department, Stanford, USA
contact emailogozani@stanford.edu
lab head
Mohamad Zoabi
contact affiliationStanford
contact emailzhamody@stanford.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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