PXD013965

PXD013965 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomic atlas of phosphorylation and ubiquitination reveals Epn2-mediated endocytosis dysfunction in α-synuclein transgenic mice
Description	Progression through neuronal loss of substantia nigra pars compacta with Parkinson’s disease depends on various protein post-translational modifications mainly comprising phosphorylation, ubiquitination, acetylation, and methylation. Phosphorylation and ubiquitination regulate major physiological changes and cellular signaling pathways during dopaminergic neuronal death. Phosphorylation and ubiquitination dyshomeostasis of substantia nigra pars compacta tissue occurs earlier than movement symptom appearance. Although many phosphorylation and ubiquitination sites have been identified through site-specific methods, systematic quantitative proteomic analysis of pre-symptomatic Parkinson’s disease remains unexplored. Using quantitative proteomics, we have globally profiled ubiquitination and phosphorylation in substantia nigra pars compacta tissue of a Parkinson’s disease transgenic mouse model (A30P*A53T α-synuclein, hm2α-SYN-39 mouse strain) at pre-symptomatic stage; Our datasets of 5,351 phosphorylation sites in 2,136 proteins and 3,971 ubiquitination sites in 1,595 proteins provide valuable insight into pre-symptomatic Parkinson’s disease. After in-depth analysis of the relationship between phosphorylation and ubiquitination sites, we concluded that correlation of the relationship increased with decreasing distance. Subsequent bioinformatic analyses, including gene ontology annotation, domain annotation, subcellular localization, KEGG pathway annotation, functional cluster analysis, and motif analysis were performed to annotate quantifiable targets of phosphorylation and ubiquitination sites. Individual simultaneous phosphorylation and ubiquitination proteins that were differentially quantified were screened. The endocytosis pathway is likely regulated by both phosphorylation and ubiquitination at the molecular protein Epn2 (S439 and K135) in early-stage Parkinson’s disease. Therefore, this elucidation of the dysregulation of phosphorylation and ubiquitination has implications for understanding the pathophysiological mechanism of dopaminergic neuron degeneration and for developing novel therapeutics for Parkinson’s disease.
HostingRepository	PRIDE
AnnounceDate	2022-02-28
AnnouncementXML	Submission_2022-02-28_08:21:14.626.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pei Zhang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-22 03:13:05	ID requested
⏵ 1	2022-02-28 08:21:15	announced

He F, Zhang L, Qi G, Zhang Q, Cai H, Li T, Li M, Ming J, Tian B, Zhang P, Global ubiquitome analysis of substantia nigra in doubly-mutant human alpha-synuclein transgenic mice. Behav Brain Res, 380():112436(2020) [pubmed]

submitter keyword: Phosphorylation, ubiquitination, quantitative proteomics, Parkinson’s disease, endocytosis

Pei Zhang
contact affiliation	Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei Province, 430030, P. R. China
contact email	zhangpei@hust.edu.cn
lab head
Pei Zhang
contact affiliation	Huazhong University of Science and Technology
contact email	zhangpei@hust.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013965
     1. Label: PRIDE project
     2. Name: Quantitative proteomic atlas of phosphorylation and ubiquitination reveals Epn2-mediated endocytosis dysfunction in α-synuclein transgenic mice