PXD002883

PXD002883 is an original dataset announced via ProteomeXchange.

Title	Combined assessment of global proteome, phosphoproteome and N-terminal protein cleavage to characterize altered platelet functions in human Scott syndrome
Description	The Scott syndrome is a rare bleeding disorder associated with a mutation in the gene encoding anoctamin-6 (TMEM16F). After stimulation of Ca2+-mobilizing agonists, syndromatic platelets show a reduced phosphatidylserine exposure and do not form membrane blebs. Given the central role of anoctamin-6 in the platelet procoagulant response, we used quantitative proteomics to understand the underlying molecular mechanisms and the complex phenotypic changes in Scott platelets compared to control platelets. Therefore, we applied an iTRAQ-based multi-pronged strategy to quantify changes in (i) the global proteome, (ii) the phosphoproteome and (iii) proteolytic events between resting and stimulated Scott and control platelets. Our data indicate a limited number of proteins with decreased (70) or increased (64) expression in Scott platelets, among those we observed the absence of anoctamin-6 and the strong up-regulation of aquaporin-1. Furthermore, the quantification of 1,566 phosphopeptides revealed major differences between Scott and control platelets after stimulation with thrombin/convulxin or ionomycin. Finally, we quantified 1,596 N-terminal peptides in activated Scott and control platelets, 180 of which we identified as calpain-regulated, whereas a distinct set of 23 neo-N-termini was caspase-regulated. In Scott platelets, calpain-induced cleavage of cytoskeleton-linked and signaling proteins was down-regulated, in accordance with an increased phosphorylation state. Thus, multi-pronged proteomic profiling of Scott platelets provides detailed insight into their protection against detrimental Ca2+-dependent changes that are normally associated with phosphatidylserine exposure.
HostingRepository	PRIDE
AnnounceDate	2016-08-24
AnnouncementXML	Submission_2016-08-24_07:55:37.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD002883
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fiorella Andrea Solari
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss: -17.026549; Gln->pyro-Glu: -17.026549; Glu->pyro-Glu: -18.010565; Oxidation: 15.994915; Carbamidomethyl: 57.021464; Acetyl: 42.010565
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-09 06:09:10	ID requested
⏵ 1	2016-08-24 07:55:38	announced

Solari FA, Mattheij NJ, Burkhart JM, Swieringa F, Collins PW, Cosemans JM, Sickmann A, Heemskerk JW, Zahedi RP, Combined Quantification of the Global Proteome, Phosphoproteome, and Proteolytic Cleavage to Characterize Altered Platelet Functions in the Human Scott Syndrome. Mol Cell Proteomics, 15(10):3154-3169(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Human platelets, proteome, phosphoproteome, N-terminal ChaFRADIC, LC-MS

Dr. René P. Zahedi
contact affiliation	Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact email	zahedi@isas.de
lab head
Fiorella Andrea Solari
contact affiliation	Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact email	fiorella.solari@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002883
     1. Label: PRIDE project
     2. Name: Combined assessment of global proteome, phosphoproteome and N-terminal protein cleavage to characterize altered platelet functions in human Scott syndrome