Proteomics

Dataset Information

0

HERC2 orchestrates assembly quality control of multimeric protein complexes via ubiquitylation of orphan subunits

ABSTRACT: Most eukaryotic proteins function as subunits within multimeric complexes. Imbalances in subunit levels disrupt assembly, leaving orphan proteins that are degraded by unclear quality control mechanisms. We identify the ubiquitin ligase HERC2 as a key regulator of this process. Proteomic analysis reveals HERC2 targets subunits from diverse complexes, including the proteasome, microtubule-associated structures, tRNA biosynthesis machinery, vesicle coats, centrosomes, Ski, and GATOR2. Focusing on the proteasome, we show that HERC2 mediates the ubiquitylation of at least eleven proteins involved in assembling the regulatory particle. Mechanistically, HERC2 recognizes unassembled subunits such as PSMC5, via interactions with chaperones like PAAF1, marking them for proteasomal degradation. Importantly, HERC2 deficiency disrupts proteasome activity in human cells, a defect also observed in patient-derived cells with HERC2-mediated neurodevelopmental disorders. These findings highlight the critical role of HERC2 in maintaining the assembly and activity of multimeric protein complexes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nerea Osinalde  

LAB HEAD: Jose Luis Rosa

PROVIDER: PXD071427 | Pride | 2026-05-25

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
JUANMA_1A_20210610_001.raw Raw
JUANMA_1B_20210610_001.raw Raw
JUANMA_1C_20210610_001.raw Raw
JUANMA_2A_20210610_001.raw Raw
JUANMA_2B_20210610_001.raw Raw
Items per page:
1 - 5 of 20
altmetric image

Publications

Biallelic hypomorphic variants in the E3 ubiquitin ligase HERC2 cause a neurodevelopmental disorder clinically resembling Angelman syndrome, characterized by global developmental delay, intellectual disability, autism spectrum features, and movement abnormalities. Defining the target substrates of HERC2 is essential for understanding its biological role and the mechanisms underlying its pathological variants. To this end, we performed a quantitative proteomic analysis using biotinylated ubiquiti  ...[more]

Similar Datasets

Proteomics Aggregation of respiratory complex subunits marks the onset of proteotoxicity in proteasome inhibited cells
2019-01-28 | PXD012204 | Pride
Transcriptomics The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKK kinases prior to complex assembly
2021-09-10 | GSE183610 | GEO
Transcriptomics Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
2025-08-04 | GSE288665 | GEO
Genomics Disruption of the SAGA CORE triggers collateral degradation of KAT2A
2026-03-16 | GSE300600 | GEO
Transcriptomics Bulk mRNA sequencing of wildtype (WT) and mutator mouse embryonic fibroblasts (MEFs)
2020-07-26 | GSE153983 | GEO
Transcriptomics Coordination and assembly of protein complexes encoded across mitochondrial and nuclear genomes is assisted by mtCLPXP in Arabidopsis thaliana
2019-12-13 | GSE141942 | GEO
Transcriptomics Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors
2024-05-01 | GSE232348 | GEO
Proteomics Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
2025-08-04 | PXD058728 | Pride
Proteomics Impact of de novo variants in the PSMC5 coding the AAA-ATPase proteasome subunit PSMC5/Rpt6 on the protein pattern of patient-derived primary T-cells in comparison to their wild-type counterparts.
2025-08-07 | PXD048558 | Pride
Genomics Multimeric nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants
| PRJNA704270 | ENA