ArticleNature communications2013
A molecular explanation for the recessive nature of parkin-linked Parkinson's disease.
Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 150 citations in OpenAlex.
- Mitochondrial metabolic reprogramming, quality control, and intercellular transfer in regulating macrophage plasticity.Frontiers in physiology · 2026Review
- Glucose concentration of neuronal media formulations influences PINK1-dependent mitophagy in human iNeurons.Autophagy reports · 2026Article
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1.The Journal of cell biology · 2025Article
- Capturing the catalytic intermediates of parkin ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Upregulated ECM genes and increased synaptic activity in Parkinson's human DA neurons with PINK1/ PRKN mutations.NPJ Parkinson's disease · 2024Article
- In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling.Biomolecules · 2024Article
- Activation of CaCell death and differentiation · 2024Article
- Structure-based design and characterization of Parkin-activating mutations.Life science alliance · 2023Article
- PINK1-PRKN mediated mitophagy: differences betweenAutophagy · 2023Review
- Parkin coregulates glutathione metabolism in adult mammalian brain.Acta neuropathologica communications · 2023Article
- Redefining the catalytic HECT domain boundaries for the HECT E3 ubiquitin ligase family.Bioscience reports · 2022Article
- Characterisation of HOIP RBR E3 ligase conformational dynamics using integrative modelling.Scientific reports · 2022Article
- Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation.Human molecular genetics · 2022Article
- Convergent Molecular Pathways in Type 2 Diabetes Mellitus and Parkinson's Disease: Insights into Mechanisms and Pathological Consequences.Molecular neurobiology · 2022Review
- Mechanism and Disease Association With a Ubiquitin Conjugating E2 Enzyme: UBE2L3.Frontiers in immunology · 2022Review
- Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria.Open biology · 2022Article
- Parkin, an E3 Ubiquitin Ligase, Plays an Essential Role in Mitochondrial Quality Control in Parkinson's Disease.Cellular and molecular neurobiology · 2021Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in the park2 gene, encoding the RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases. More than 70 known pathogenic mutations occur throughout parkin, many of which cluster in the inhibitory amino-terminal ubiquitin-like domain, and the carboxy-terminal RING2 domain that is indispensable for ubiquitin transfer. A structural rationale showing how autosomal recessive juvenile Parkinsonism mutations alter parkin function is still lacking. Here we show that the structure of parkin RING2 is distinct from canonical RING E3 ligases and lacks key elements required for E2-conjugating enzyme recruitment. Several pathogenic mutations in RING2 alter the environment of a single surface-exposed catalytic cysteine to inhibit ubiquitination. Native parkin adopts a globular inhibited conformation in solution facilitated by the association of the ubiquitin-like domain with the RING-inBetweenRING-RING C-terminus. Autosomal recessive juvenile Parkinsonism mutations disrupt this conformation. Finally, parkin autoubiquitinates only in cis, providing a molecular explanation for the recessive nature of autosomal recessive juvenile Parkinsonism.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.