PXD045466-1

PXD045466 is an original dataset announced via ProteomeXchange.

Title	The fitness cost of spurious phosphorylation
Description	The fidelity of signal transmission requires the binding of regulatory molecules to their cognate targets. However, the crowded cell interior risks off-target interactions between proteins that are functionally unrelated. Understanding the constraints this imposes on cell systems evolution requires the fitness cost of spurious interactions to be quantified. Towards this end, we express human tyrosine kinases in the budding yeast S. cerevisiae. Yeast lacks bona fide tyrosine kinases and so the majority of resulting pY sites are functionless and artificial. We express 24 unique tyrosine kinases in total and perform phosphoproteomics in each case, resulting in ~30,000 phosphosites sites mapping to 3500 phosphoproteins. Examination of the fitness costs in each strain reveals a strong correlation between the number of spurious pY sites generated and negative effects on growth. Moreover, the prediction of pY effects on protein structure and on protein function (conservation-based) reveals potential for the widespread perturbation of the yeast proteome. Comparing the spurious pY sites (pre-selection) with native pY sites in human (post-selection) also demonstrates the recurrent modification of proteins and sites with no homology to native substrates. However, examination of these data together (fitness and phosphoproteomics) strongly suggests that a large number of the pY sites generated have a negligible effect on fitness. Finally, we test the hypothesis of pY counter-selection following the emergence of tyrosine kinases in metazoan species, but find no strong evidence for proteome-wide selection against spurious Y phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2024-09-12
AnnouncementXML	Submission_2024-09-12_13:46:17.682.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexander Hogrebe
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-18 06:26:02	ID requested
⏵ 1	2024-09-12 13:46:18	announced

10.1038/s44318-024-00200-7;

Bradley D, Hogrebe A, Dandage R, Dub, é AK, Leutert M, Dionne U, Chang A, Vill, é, n J, Landry CR, The fitness cost of spurious phosphorylation. EMBO J, 43(20):4720-4751(2024) [pubmed]

submitter keyword: spurious, human, LCMS, phosphotyrosine,yeast

Judit Villén
contact affiliation	Department of Genome Sciences, University of Washington, Seattle, WA, USA
contact email	jvillen@uw.edu
lab head
Alexander Hogrebe
contact affiliation	MSAID GmbH
contact email	ahogrebe@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045466
     1. Label: PRIDE project
     2. Name: The fitness cost of spurious phosphorylation