PXD056466

PXD056466 is an original dataset announced via ProteomeXchange.

Title	SMYD5 is a ribosomal methyltransferase which trimethylates RPL40 lysine 22 through recognition of a KXY motif
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2025-04-07
AnnouncementXML	Submission_2025-04-06_21:15:07.371.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joshua Hamey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; N6; dimethylated residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-02 19:41:11	ID requested
⏵ 1	2025-04-06 21:15:07	announced

10.1016/J.CELREP.2025.115518;

submitter keyword: Ribosome, lysine methylation, substrate specificity, translation, methyltransferase

Marc Wilkins
contact affiliation	University of New South Wales
contact email	m.wilkins@unsw.edu.au
lab head
Joshua Hamey
contact affiliation	University of New South Wales
contact email	j.hamey@unsw.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056466
     1. Label: PRIDE project
     2. Name: SMYD5 is a ribosomal methyltransferase which trimethylates RPL40 lysine 22 through recognition of a KXY motif