PXD009201

PXD009201 is an original dataset announced via ProteomeXchange.

Title	A systemic view of active site specificity profiling of the snake venom metalloprotease HF3 using Proteomic Identification of Cleavage Sites and N-terminomics TAILS
Description	Snake venom metalloproteinases play important roles in the pathological effects of Viperidae venoms including severe local tissue damage, hemorrhage and coagulopathy. Hemorrhagic Factor 3 (HF3), a metalloproteinase isolated from Bothrops jararaca venom, induces severe local hemorrhage. Previous proteomic studies have shown that HF3 targets important ECM components, including collagens and proteoglycans, and plasma proteins. However, the full substrate repertoire of this metalloproteinase is unknown. Using Proteomic Identification of Cleavage Sites (PICS), a tryptic library derived from THP-1 monocytic cells was used as substrate for identifying protease cleavage sites and sequence preferences in peptides. 1,252 cleavage sites were detected and revealed a clear preference for Leu at P1′ position. A Terminal Amine Isotopic Labeling of Substrates (TAILS) analysis of the incubation of HF3 with mouse embryonic fibroblasts (MEF) secretome resulted in the identification of more than 3,600 cleavage sites in proteins, and confirmed the predominance of Leu at P1′ position. Various substrates were detected including ECM and focal adhesion proteins, and the cysteine proteinase inhibitor, cystatin-C. Interestingly, 597 peptides matched to annotated cleavage sites in the TopFIND database, suggesting that these cleavages might have been generated by other proteases activated upon incubation with HF3, including caspases -3 and -7, cathepsins D and E, granzyme B, and MMPs 2 and 9. Taken together, these results greatly expand the known substrate degradome of HF3, and reveals potential new targets which may serve as basis to better elucidate the complex pathophysiology of snake envenomation.
HostingRepository	PRIDE
AnnounceDate	2019-07-29
AnnouncementXML	Submission_2019-07-29_07:05:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andre Zelanis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	thioacylation of primary amines - site N-term; N6 N6-dimethyl-L-lysine; 2x(13)C; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-13 08:19:01	ID requested
⏵ 1	2019-07-29 07:05:19	announced

Zelanis A, Oliveira AK, Prudova A, Huesgen PF, Tashima AK, Kizhakkedathu J, Overall CM, Serrano SMT, Deep Profiling of the Cleavage Specificity and Human Substrates of Snake Venom Metalloprotease HF3 by Proteomic Identification of Cleavage Site Specificity (PICS) Using Proteome Derived Peptide Libraries and Terminal Amine Isotopic Labeling of Substrates (TAILS) N-Terminomics. J Proteome Res, 18(9):3419-3428(2019) [pubmed]

curator keyword: Biological

submitter keyword: snake venom, snake venom metalloprotease, HF3, degradomics, N-terminome, TAILS

Solange M.T Serrano
contact affiliation	Laboratório Especial de Toxinologia Aplicada, Instituto Butantan,Av. Vital Brasil 1500, 05503-000, São Paulo, Brazil.
contact email	solange.serrano@butantan.gov.br
lab head
Andre Zelanis
contact affiliation	Laboratory of Functional Proteomics - Department of Science and Technology - Federal University of São Paulo (UNIFESP), Sao Jose dos Campos-SP, Brazil
contact email	zelanis@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/07/PXD009201

PRIDE project URI

• PRIDE
  1. PXD009201
     1. Label: PRIDE project
     2. Name: A systemic view of active site specificity profiling of the snake venom metalloprotease HF3 using Proteomic Identification of Cleavage Sites and N-terminomics TAILS