PXD031408-1

PXD031408 is an original dataset announced via ProteomeXchange.

Title	Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity
Description	Sulfs represent a class of unconventional sulfatases, which differ from all other members of the sulfatase family by their structures, catalytic features and biological functions. Through their specific endosulfatase activity in extracellular milieu, Sulfs provide an original post-synthetic regulatory mechanism for heparan sulfate complex polysaccharides and have been involved in multiple physiopathological processes, including cancer. However, Sulfs remain poorly characterized enzymes, with major discrepancies regarding their in vivo functions. Here we show that human Sulf-2 (HSulf-2) features a unique polysaccharide post-translational modification. We identified a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, attached to the enzyme substrate binding domain. We found that this GAG chain affects enzyme/substrate recognition and tunes HSulf-2 activity in vitro and in vivo using a mouse model of tumorigenesis and metastasis. In addition, we showed that mammalian hyaluronidase acted as a promoter of HSulf-2 activity by digesting its GAG chain. In conclusion, our results highlight HSulf-2 as a unique proteoglycan enzyme and its newly-identified GAG chain as a critical non-catalytic modulator of the enzyme activity. These findings contribute in clarifying the conflicting data on the activities of the Sulfs and introduce a new paradigm into the study of these enzymes.
HostingRepository	PRIDE
AnnounceDate	2022-03-18
AnnouncementXML	Submission_2022-03-18_08:13:30.326.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Core Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-03 07:31:23	ID requested
⏵ 1	2022-03-18 08:13:30	announced

Dataset with its publication pending

submitter keyword: sulfatase, enzyme, glycosaminoglycan, proteoglycan, post-translational modifications

Romain R. Vivès
contact affiliation	Univ. Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France
contact email	romain.vives@ibs.fr
lab head
Proteomics Core Facility
contact affiliation	SAMBIO Core Facilities, Sahgrenska Academy, University of Gothenburg
contact email	gupcf@outlook.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/2022/03/PXD031408

PRIDE project URI

• PRIDE
  1. PXD031408
     1. Label: PRIDE project
     2. Name: Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity