LIRcentral - Home

Members of the Atg8 protein family (1) are small proteins with a ubiquitin-like fold and are key components of the macroautophagy machinery, participating essentially in all steps of macroautophagy from phagophore nucleation, to autolysosome formation (2). They are involved in an increasing number of biological processes, including LC3-associated phagocytosis (3, 4), endosomal microautophagy (4, 5), and unconventional secretion (6).

In selective macroautophagy, selectivity is mainly achieved through receptor proteins that bind to the surface of Atg8 by anchoring a small linear peptide (AIM in plants and fungi, LIR-motif in mammals) (7). After the discovery of the first few LIR-containing proteins (LIRCPs), several definitions of the LIR-motif have appeared in the literature, highlighting a short core consensus sequence described by the regular expression pattern [WFY]xx[VLI] (8, 9, 10, 11, 12). Accumulating experimental evidence pinpoints the importance of regions flanking the core LIR-motif, while several instances of atypical LIR-motifs and LIR-independent interactions are being uncovered.

We have developed LIRcentral as a publicly available, comprehensive collection of experimentally confirmed LIR-motifs, based on extensive biomedical literature search, assisted by text mining techniques and careful manual curation. Interested researchers are able to retrieve information about literature-validated LIR-motifs and display them along with sequence features annotated in UniProt. For more details on the LIRcentral content, the curation process and other interesting features, please see the publication of the LIRcentral team (13). A pre-print describing LIRcentral is available in bioRxiv.

References

  1. Shpilka T, Weidberg H, Pietrokovski S, Elazar Z. Atg8: an autophagy-related ubiquitin-like protein family. Genome Biol. 2011 Jul 27;12(7):226.
  2. Johansen T, Lamark T. Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors. J Mol Biol. 2020 Jan 3;432(1):80-103.
  3. Heckmann BL, Green DR. LC3-associated phagocytosis at a glance. J Cell Sci 2019; 132:jcs222984.
  4. Nieto-Torres JL, Leidal AM, Debnath J, Hansen M. Beyond autophagy: The expanding roles of ATG8 proteins. Trends Biochem Sci 2021; 46:673-686.
  5. Mejlvang J, Olsvik H, Svenning S, Bruun JA, Abudu YP, Larsen KB, Brech A, Hansen TE, Brenne H, Hansen T, Stenmark H, Johansen T. Starvation induces rapid degradation of selective autophagy receptors by endosomal microautophagy. J Cell Biol 2018; 217:3640-3655.
  6. Claude-Taupin A, Jia J, Mudd M, Deretic V. Autophagy's secret life: Secretion instead of degradation. Essays Biochem 2017; 61:637-647.
  7. Wesch N, Kirkin V, Rogov VV. Atg8-family proteins-structural features and molecular interactions in autophagy and beyond. Cells 2020; 9:2008.
  8. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Øvervatn A, Bjørkøy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282:24131-24145.
  9. Ichimura Y, Kominami E, Tanaka K, Komatsu M. Selective turnover of p62/A170/SQSTM1 by autophagy. Autophagy 2008; 4:1063-1066.
  10. Noda NN, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, Fujioka Y, Ohsumi Y, Inagaki F. Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells 2008; 13:1211-1218.
  11. Noda NN, Ohsumi Y, Inagaki F. Atg8-family interacting motif crucial for selective autophagy. FEBS Lett 2010; 584:1379-1385.
  12. Alemu EA, Lamark T, Torgersen KM, Birgisdottir AB, Larsen KB, Jain A, Olsvik H, Øvervatn A, Kirkin V, Johansen T. ATG8 family proteins act as scaffolds for assembly of the ULK complex: Sequence requirements for LC3-interacting region (LIR) motifs. J Biol Chem 2012; 287:39275-39290.
  13. Chatzichristofi, A., Sagris, V., Pallaris, A., Eftychiou, M., Kalvari, I., Price, N., Theodosiou, T., Iliopoulos, I., Nezis, I. P., & Promponas, V. J. LIRcentral: a manually curated online database of experimentally validated functional LIR motifs. Autophagy 2023; 19(12), 3189–3200.

Bioinformatics Research Laboratory

LIRcentral is co-funded by the European Union (European Regional Development Fund, ERDF) and the Republic of Cyprus through the project EXCELLENCE/0421/0576 under the EXCELLENCE HUBS programme of the Cyprus Research and Innovation Foundation.

University of Cyprus