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PXD023984

PXD023984 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleER-associated degradation of Eag1 potassium channels by the RING E3 ubiquitin ligase MKRN1: the presence of a dual ubiquitination system
DescriptionMutations 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:29:20.577.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD023984
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterChen-Chung Liao
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLCQ Classic
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-02-04 00:08:00ID requested
12021-09-10 00:39:53announced
22024-10-22 05:29:21announced2024-10-22: Updated project metadata.
Publication List
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;
Keyword List
submitter keyword: RING E3, MKRN1
Contact List
Chen-Chung Liao
contact affiliationNational Yang-Ming University, Proteomics Research Center, Taipei City, Taiwan
contact emailccliao@ym.edu.tw
lab head
Chen-Chung Liao
contact affiliationProteomics Research Center,National Yang-Ming University
contact emailccliao@ym.edu.tw
dataset submitter
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