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

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.

Atg8家族蛋白是目前研究最为透彻的核心自噬机器蛋白。它们对于将吞噬泡（phagophore）延伸并闭合为正常自噬体（autophagosome）至关重要。不仅如此，从自噬过程启动直至自噬体与溶酶体（lysosome）融合前的瞬间，Atg8家族蛋白始终与吞噬泡相关联。除参与自噬体的生物发生过程外，Atg8家族蛋白还可通过结合选择性自噬受体蛋白，在选择性自噬中发挥关键作用——这类受体蛋白是介导底物特异性靶向以进行自噬降解所必需的。
过去数年间的研究揭示，Atg8互作蛋白不仅涵盖自噬受体，还包括核心自噬机器组分、囊泡及其转运相关蛋白，以及经自噬选择性降解的特定蛋白。Atg8互作蛋白均含有一段短的线性LC3互作区域/LC3识别序列/Atg8互作基序（LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif, LIR/LRS/AIM），该基序负责介导其与Atg8家族蛋白的相互作用。这类蛋白被统称为含LIR基序蛋白（LIR-containing proteins, LIRCPs）。
截至目前，学界已开展大量实验工作以鉴定新型LIRCPs，并在过去十年间对其中部分蛋白完成了功能表征。鉴于亟需在多种生物中鉴定LIRCPs，我们开发了iLIR数据库（https://ilir.warwick.ac.uk）作为免费开放的网络资源，收录了通过iLIR服务器在8种模式生物（model organisms）的蛋白质组（proteome）中经计算机预测（in silico）鉴定出的所有候选经典LIRCPs，并结合了基因本体（Gene Ontology, GO）术语分析。此外，通过对已发表文献进行人工甄选的文本挖掘分析，我们还在哺乳动物中鉴定出了此前未被报道与自噬相关的新型候选LIRCPs。

搜集汇总

背景与挑战

背景概述

iLIR database是一个专注于真核生物中LIR motif-containing proteins的在线数据库资源，通过计算机模拟和文献挖掘识别了8种模式生物中的潜在LIRCPs，并提供了基因本体论分析。该数据库旨在帮助研究人员识别与自噬相关的蛋白质相互作用。