ArticleAutophagy2020
An atypical LIR motif within UBA5 (ubiquitin like modifier activating enzyme 5) interacts with GABARAP proteins and mediates membrane localization of UBA5.
Article in Autophagy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- The UFSP2-C1orf27 complex positions nascent GPCRs to the ufmylation system for ER export control.iScience · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- A non-canonical ARMS-GABARAP interaction modulates dendritic spine formation and synaptic development.The EMBO journal · 2026Article
- SQSTM1/p62 UFMylation Enhances Autophagic Clearance of Pathogenic Mutant Huntingtin.International journal of biological sciences · 2026Article
- UFM1 at the endoplasmic reticulum: linking ER stress, ribosome quality control, and ER-phagy.Essays in biochemistry · 2025Review
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- AlphaFold2 SLiM screen for LC3-LIR interactions in autophagy.Autophagy · 2025Article
- The rapidly expanding role of LC3-interacting regions in autophagy.The Journal of cell biology · 2025Review
- RAB33A promotes metastasis via RhoC accumulation through non-canonical autophagy in cervical cancer.Cell death & disease · 2025Article
- Exploring the multilayered response of TB bacterium Mycobacterial tuberculosis to lysosomal injury.FEMS microbiology reviews · 2025Review
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- The ufmylation cascade controls COPII recruitment, anterograde transport, and sorting of nascent GPCRs at ER.Science advances · 2024Article
- A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.Molecular and cellular biochemistry · 2024Review
- Atg8 family proteins, LIR/AIM motifs and other interaction modes.Autophagy reports · 2023Article
- Computed Protein-Protein Enthalpy Signatures as a Tool for Identifying Conformation Sampling Problems.Journal of chemical information and modeling · 2023Article
- Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical LC3 Interacting Region Motif Crucial for the Enzymatic Activity of Human ATG3.ACS central science · 2023Article
- Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and autophagy.The EMBO journal · 2023Article
- Dysregulation of ribosome-associated quality control elicits cognitive disorders via overaccumulation of TTC3.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Short linear motifs, known as LC3-interacting regions (LIRs), interact with mactoautophagy/autophagy modifiers (Atg8/LC3/GABARAP proteins) via a conserved universal mechanism. Typically, this includes the occupancy of 2 hydrophobic pockets on the surface of Atg8-family proteins by 2 specific aromatic and hydrophobic residues within the LIR motifs. Here, we describe an alternative mechanism of Atg8-family protein interaction with the non-canonical UBA5 LIR, an E1-like enzyme of the ufmylation pathway that preferentially interacts with GABARAP but not LC3 proteins. By solving the structures of both GABARAP and GABARAPL2 in complex with the UBA5 LIR, we show that in addition to the binding to the 2 canonical hydrophobic pockets (HP1 and HP2), a conserved tryptophan residue N-terminal of the LIR core sequence binds into a novel hydrophobic pocket on the surface of GABARAP proteins, which we term HP0. This mode of action is unique for UBA5 and accompanied by large rearrangements of key residues including the side chains of the gate-keeping K46 and the adjacent K/R47 in GABARAP proteins. Swapping mutations in LC3B and GABARAPL2 revealed that K/R47 is the key residue in the specific binding of GABARAP proteins to UBA5, with synergetic contributions of the composition and dynamics of the loop L3. Finally, we elucidate the physiological relevance of the interaction and show that GABARAP proteins regulate the localization and function of UBA5 on the endoplasmic reticulum membrane in a lipidation-independent manner.
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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.