PXD020821

PXD020821 is an original dataset announced via ProteomeXchange.

Title	Proteom-wide analysis of lysine N-homocysteinylation and Hcy-induced proteom changes in Saccharomyces cerevisiae
Description	Hyperhomocysteinemia (HHcy) inhibits growth and is cytotoxic to bacterial, yeast, and mammalian cells. The aim of this study was to determine the changes in proteome of the yeast induced by HHcy and map N-homocysteinylated sites. We identified 38 up- and 32-down-regulated proteins as well as 244 N-homocysteinylation sites in 98 proteins in Saccharomyces cerevisiae; with 57 sites in 34 proteins occurring in vivo. The bioinformatics analysis indicated that the N-homocysteinylated proteins were involved in a wide range of cellular functions with mostly cytosolic and ribosomal localizations. Furthermore, we discovered that lysine N-homocysteinylation sites are surrounded by neutral, hydrophobic and buried amino acid residues, and 60% of them occur within helix. The KEGG enrichment pathway analysis of these N-Hcy-proteins suggested that N-homocysteinylation disrupts metabolism of amino acids, ribosome biogenesis and glycolysis/gluconeogenesis. These findings suggest that protein N-homocysteinylation and dysregulation of cellular proteostasis affecting ribosomal proteins, biosynthesis of amino acids and changes in basic cellular pathways signaling are involved in the toxicity of HHcy in yeast. Homologous proteins are likely to be involved in HHcy toxicity in human and animal cells. We believe that the collection of N-homocysteinylation sites presented here is an important resource for future functional studies of N-homocysteinylation in yeast.
HostingRepository	PRIDE
AnnounceDate	2021-04-08
AnnouncementXML	Submission_2021-04-08_03:13:12.498.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020821
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Agata Malinowska
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Equus caballus (Horse); NCBI TaxID: 9796; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monomethylated residue; methylthiolated residue; ubiquitination signature dipeptidyl lysine; iTRAQ8plex-116 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-10 04:16:25	ID requested
⏵ 1	2021-04-08 03:13:13	announced

Perl A-Kaj, á, n J, Malinowska A, Zimny JA, Cysewski D, Suszy, ń, ska-Zajczyk J, Jakubowski H, . J Proteome Res, 20(5):2458-2476(2021) [pubmed]

submitter keyword: N-homocysteinylation, homocysteine, homocysteine thiolactone, yeast proteome

Michal Dadlez
contact affiliation	Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
contact email	michald@ibb.waw.pl
lab head
Agata Malinowska
contact affiliation	IBB PAS
contact email	esme@ibb.waw.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020821
     1. Label: PRIDE project
     2. Name: Proteom-wide analysis of lysine N-homocysteinylation and Hcy-induced proteom changes in Saccharomyces cerevisiae