iLIR database: A web resource for LIR motif-containing proteins in eukaryotes

Abstract

Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database (https://ilir.warwick.ac.uk) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy.

The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

“…We retained only those interactions identified by at least two of the studies annotated in the database. We then predicted LIR motifs for each of the interactors through the iLIR database (Jacomin et al, 2016) and retained only those with a score higher than 11. This threshold was selected as it allows for a higher sensitivity (92%) at price of slightly lower specificity (Jacomin et al, 2016).…”

“…We then predicted LIR motifs for each of the interactors through the iLIR database (Jacomin et al, 2016) and retained only those with a score higher than 11. This threshold was selected as it allows for a higher sensitivity (92%) at price of slightly lower specificity (Jacomin et al, 2016). We also verified through literature search if any of the interactors include one or more already experimentally verified LIR motifs (see Supplementary File 14).…”

mTORC1-Plin3 pathway is essential to activate lipophagy and protects against hepatosteatosis

“…Specifically, Plin3 is required for the recruitment and assembly of protein components of the autophagy machinery to LD in response to lipid loading. Whilst Plin3 does not contain a putative LIR motif to mediate its interaction with LC3 (Jacomin, Samavedam, Promponas and Nezis, 2016), other non-canonical autophagy receptors have recently been described. For example, CCPG1 binds to FIP200 instead of LC3 to promote ER-Phagy in the pancreas Wilkinson, 2018, Smith, Harley, Kemp, Wills, Lee, Arends, von Kriegsheim, Behrends and.…”

LIR-dependent LMX1A/LMX1B autophagy crosstalk shapes human midbrain dopaminergic neuronal resilience

“…probability index), and sequences with relative scores >80%-a commonly used threshold for TFBS (computational framework for transcription factor binding site) analyses using PSSMs (Position Specific Scoring Matrix). To identify putative LMX1A/B LC3-interacting regions (LIR motifs), we used the iLIR Autophagy database (https://ilir.warwick.ac.uk) (Jacomin, Samavedam et al, 2016), applying ANCHOR software to predict flanking, stabilisation regions predicted to stabilize the putative binding. To identify the NLS sequence in LMX1A and LMX1B, we used the cNLS Mapper (Kosugi, Hasebe et al, 2009) which predicted the NLS sequence with a score of 7 and 10, respectively.…”