PXD002883 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-09-09 06:09:10 | ID requested | |
⏵ 1 | 2016-08-24 07:55:38 | announced | |
Publication List
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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Human platelets, proteome, phosphoproteome, N-terminal ChaFRADIC, LC-MS |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002883
- Label: PRIDE project
- Name: Combined assessment of global proteome, phosphoproteome and N-terminal protein cleavage to characterize altered platelet functions in human Scott syndrome