PXD071427 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | HERC2 orchestrates assembly quality control of multimeric protein complexes via ubiquitylation of orphan subunits |
| Description | 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. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-05-25 |
| AnnouncementXML | Submission_2026-05-24_17:25:46.063.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Nerea Osinalde |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | ubiquitination signature dipeptidyl lysine |
| Instrument | Q Exactive HF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-12-01 05:59:57 | ID requested | |
| ⏵ 1 | 2026-05-24 17:25:46 | announced | |
Publication List
| Sala-Gaston J, Costa-Sastre L, Garcia-Diez M, L, ó, pez-Hern, á, ndez T, Ram, í, rez J, Osinalde N, Valer JA, Arnedo-Pac C, Crosas B, Baple EL, Crosby AH, Mayor U, Ventura F, Rosa JL, Proteasome dysfunction underlies HERC2-linked neurodevelopmental disorder with Angelman-like clinical features. Cell Death Discov, 12(1):(2026) [pubmed] |
| 10.1038/s41420-026-03095-x; |
Keyword List
| submitter keyword: Assembly quality control, multi-protein complexes, protein stability, ligase, bioUb., HERC, proteasome, ubiquitin |
Contact List
| Jose Luis Rosa |
|---|
| contact affiliation | Department of Physiological Sciences, University of Barcelona, IDIBELL, Spain |
| contact email | joseluisrosa@ub.edu |
| lab head | |
| Nerea Osinalde |
|---|
| contact affiliation | Teacher/Researcher |
| contact email | nerea.osinalde@ehu.eus |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD071427
- Label: PRIDE project
- Name: HERC2 orchestrates assembly quality control of multimeric protein complexes via ubiquitylation of orphan subunits
