PXD001672

PXD001672 is an original dataset announced via ProteomeXchange.

Title	SPPL3 cleavage of glycosyltransferases regulates their activity
Description	The GxGD intramembrane-cleaving aspartylprotease signal peptide peptidase-like 3 (SPPL3) is a Golgi-resident, multi-pass membrane protein that is highly conserved among multicellular eukaryotes pointing to a pivotal physiological function in the Golgi network. Recently, the key branching enzyme N-acetylglucosaminyltransferase V (GnT-V) and other medial/trans Golgi glycosyltransferases were identified as first physiological SPPL3 substrates. SPPL3-mediated endoproteolysis releases these enzymes from their type II membrane anchors resulting in a subsequent secretion of the respective enzymes’ ectodomain. To systematically identify further SPPL3 substrates we used the secretome protein enrichment with click sugars (SPECS) method that makes secretomes of cultured cells accessible to mass spectrometric analyses. SPECS analyses of SPPL3-deficient and SPPL3-overexpression cell culture models revealed numerous additional SPPL3 candidate substrates and their subsequent biochemical validation underscores the role of SPPL3 in secretion of these proteins. In line with our previous observations, all novel SPPL3 substrates adopt a type II topology and the majority localizes to the Golgi network and is implicated in Golgi function. Importantly, most of the novel SPPL3 substrates catalyze the modification of N-linked glycans but also of O-glycans and glycosaminoglycans. Hence, SPPL3 emerges as a crucial player of Golgi function and the newly identified SPPL3 substrates will be instrumental to investigate the molecular mechanisms underlying the physiological function of SPPL3 in the Golgi network and in vivo.
HostingRepository	PRIDE
AnnounceDate	2015-05-08
AnnouncementXML	Submission_2015-05-08_10:15:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peer-Hendrik Kuhn
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-01-13 03:39:55	ID requested
⏵ 1	2015-05-08 10:15:08	announced

Kuhn PH, Voss M, Haug-Kr, ö, per M, Schr, ö, der B, Schepers U, Br, ä, se S, Haass C, Lichtenthaler SF, Fluhrer R, Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways. Mol Cell Proteomics, 14(6):1584-98(2015) [pubmed]

curator keyword: Biological

submitter keyword: SPPL3, protease, substrates, SPECS

Prof. Dr. Stefan Lichtenthaler
contact affiliation	DZNE Muenchen, Neuroproteomik
contact email	Stefan.Lichtenthaler@dzne.de
lab head
Peer-Hendrik Kuhn
contact affiliation	DZNE München
contact email	peerhendrik@gmx.net
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001672
     1. Label: PRIDE project
     2. Name: SPPL3 cleavage of glycosyltransferases regulates their activity