PXD023984

PXD023984 is an original dataset announced via ProteomeXchange.

Title	ER-associated degradation of Eag1 potassium channels by the RING E3 ubiquitin ligase MKRN1: the presence of a dual ubiquitination system
Description	Mutations in the human gene encoding the neuron-specific Eag1 voltage-gated K+ channel are associated with neurodevelopmental diseases, indicating an important role of Eag1 during brain development. A disease-causing Eag1 mutant channel is linked to defective protein stability that involves enhanced protein degradation by the E3 ubiquitin ligase cullin 7 (CUL7). The detailed mechanisms governing protein homeostasis of plasma membrane- and endoplasmic reticulum (ER)-localized Eag1 K+ channels, however, remains unclear. By using yeast two-hybrid screening, we identified another E3 ubiquitin ligase, makorin ring finger protein 1 (MKRN1), as a novel binding partner primarily interacting with the carboxyl-terminal region of Eag1. MKRN1 mainly interacts with ER-localized immature core-glycosylated, as well as nascent non-glycosylated, Eag1 proteins. MKRN1 promotes polyubiquitination and ER-associated proteasomal degradation of immature Eag1 proteins. Although both CUL7 and MKRN1 contribute to ER quality control of immature core-glycosylated Eag1 proteins, MKRN1, but not CUL7, associates with and promotes degradation of nascent, non-glycosylated Eag1 proteins at the ER. In direct contrast to the role of CUL7 in regulating both ER and peripheral quality controls of Eag1, MKRN1 is exclusively responsible for the early stage of Eag1 maturation at the ER. We further demonstrated that both CUL7 and MKRN1 contribute to protein quality control of additional disease-causing Eag1 mutants associated with defective protein homeostasis. Our data suggest that the presence of this dual ubiquitination system differentially maintains Eag1 protein homeostasis and may ensure efficient removal of disease-associated misfolded Eag1 mutant channels.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:29:20.577.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023984
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Chen-Chung Liao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LCQ Classic

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-04 00:08:00	ID requested
1	2021-09-10 00:39:53	announced
⏵ 2	2024-10-22 05:29:21	announced	2024-10-22: Updated project metadata.

10.6019/PXD023984;

Fang YC, Fu SJ, Hsu PH, Chang PT, Huang JJ, Chiu YC, Liao YF, Jow GM, Tang CY, Jeng CJ, Identification of MKRN1 as a second E3 ligase for Eag1 potassium channels reveals regulation via differential degradation. J Biol Chem, 296():100484(2021) [pubmed]

10.1016/j.jbc.2021.100484;

submitter keyword: RING E3, MKRN1

Chen-Chung Liao
contact affiliation	National Yang-Ming University, Proteomics Research Center, Taipei City, Taiwan
contact email	ccliao@ym.edu.tw
lab head
Chen-Chung Liao
contact affiliation	Proteomics Research Center,National Yang-Ming University
contact email	ccliao@ym.edu.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023984
     1. Label: PRIDE project
     2. Name: ER-associated degradation of Eag1 potassium channels by the RING E3 ubiquitin ligase MKRN1: the presence of a dual ubiquitination system