PXD041803

PXD041803 is an original dataset announced via ProteomeXchange.

Title	Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its vital importance in the biogenesis of glycosylphosphatidylinositol-anchored proteins
Description	The SEL1L-HRD1 protein complex of endoplasmic reticulum (ER)-associated degradation (ERAD) plays indispensable roles for many physiological processes in a substrate-specific manner; however, the nature of endogenous substrates remains largely elusive. Here we have developed a unique proteomics strategy based on the intrinsic property of the SEL1L-HRD1 ERAD complex to identify potential endogenous ERAD substrates in human kidney cell line HEK293T and mouse brown adipocytes. Over 100 potential substrates involved in many cellular processes, including both membrane and luminal proteins regardless of their glycosylation and disulfide bond status, are identified in each cell type, among which 34 are shared. We further uncover SEL1L-HRD1 ERAD as a suppressor of the biogenesis of glycosylphosphatidylinositol (GPI)-anchored proteins via degrading a key subunit of the GPI-transamidase complex known as phosphatidylinositol glycan anchor biosynthesis class K protein (PIGK). Lastly, several PIGK disease variants are highly unstable and quickly degraded by SEL1L-HRD1 ERAD. This study shows the most effective way to identify cell type-specific proteome-wide potential endogenous SEL1L-HRD1 substrates, and uncovers a new function of SEL1L-HRD1 ERAD in the biogenesis and disease pathogenesis associated with GPI-anchored proteins
HostingRepository	PRIDE
AnnounceDate	2023-12-17
AnnouncementXML	Submission_2023-12-17_11:26:34.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaoqiong Wei
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-25 15:36:38	ID requested
⏵ 1	2023-12-17 11:26:35	announced

Dataset with its publication pending

submitter keyword: endogenous substrates, PIGK, disease mutants  ,SEL1L-HRD1 ERAD, proteomic screens, GPI-anchored proteins

Ling Qi
contact affiliation	Department of Molecular & Integrative Physiology,University of Michigan Medical School, 5325 Brehm Tower, 1000 Wall St., Ann Arbor, MI, 48105
contact email	lingq@umich.edu
lab head
Xiaoqiong Wei
contact affiliation	University of Michigan
contact email	weixi@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041803
     1. Label: PRIDE project
     2. Name: Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its vital importance in the biogenesis of glycosylphosphatidylinositol-anchored proteins