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PXD056466

PXD056466 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSMYD5 is a ribosomal methyltransferase which trimethylates RPL40 lysine 22 through recognition of a KXY motif
DescriptionThe eukaryotic ribosome is highly modified by protein methylation, yet many of the responsible methyltransferases remain unknown. Here we have identified SMYD5 as a ribosomal protein methyltransferase that catalyses trimethylation of RPL40 at lysine 22. Through a systematic mass spectrometry-based approach, we show that the human ribosome has 12 primary sites of protein methylation, including at RPL40 K22. Through in vitro methylation of synthetic RPL40 using fractionated lysate, we then identify SMYD5 as a candidate RPL40 K22 methyltransferase. We show that recombinant SMYD5 has robust activity towards RPL40 K22 in vitro, and that active site mutations ablate this activity. Knockouts of SMYD5 in K562 cells show a complete loss of RPL40 K22 methylation and decrease polysome levels. By systematic analysis of its recognition motif, we show that SMYD5 requires a tyrosine in the +2 position, and thereby is incapable of methylating its previously reported histone substrates.
HostingRepositoryPRIDE
AnnounceDate2025-04-07
AnnouncementXMLSubmission_2025-04-06_21:15:07.371.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJoshua Hamey
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonomethylated residue; N6; dimethylated residue
InstrumentOrbitrap Fusion Lumos; LTQ Orbitrap Velos; Q Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-02 19:41:11ID requested
12025-04-06 21:15:07announced
Publication List
10.1016/J.CELREP.2025.115518;
Keyword List
submitter keyword: Ribosome, lysine methylation, substrate specificity, translation, methyltransferase
Contact List
Marc Wilkins
contact affiliationUniversity of New South Wales
contact emailm.wilkins@unsw.edu.au
lab head
Joshua Hamey
contact affiliationUniversity of New South Wales
contact emailj.hamey@unsw.edu.au
dataset submitter
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Dataset FTP location
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