The eukaryotic linear motif resource - 2018 update

Abstract

Short linear motifs (SLiMs) are protein binding modules that play major roles in almost all cellular processes. SLiMs are short, often highly degenerate, difficult to characterize and hard to detect. The eukaryotic linear motif (ELM) resource (elm.eu.org) is dedicated to SLiMs, consisting of a manually curated database of over 275 motif classes and over 3000 motif instances, and a pipeline to discover candidate SLiMs in protein sequences. For 15 years, ELM has been one of the major resources for motif research. In this database update, we present the latest additions to the database including 32 new motif classes, and new features including Uniprot and Reactome integration. Finally, to help provide cellular context, we present some biological insights about SLiMs in the cell cycle, as targets for bacterial pathogenicity and their functionality in the human kinome.

Figure 1.

The number of SLiMs (motif classes and motif instances) created and modified in ELM. For the past 15 years, ELM has been steadily growing, and the total number of motif classes (dark orange) and motif instances (dark purple) continues to grow each year. As of September 2017, there are over 275 motif classes defined, and over 3000 motif instances annotated. Besides contributing new content, curators also updated existing annotations to include new findings (last modification dates for motif classes in dashed light purple and for motif instances in dashed light orange).

Figure 2.

SLiMs play major roles in many biological pathways, including those involved in the progression of the cell cycle. Using the Reactome pathway annotations downloaded from ELM and using Cytoscape (42) to visualize the data, we can see that many SLiMs (especially Ligand and Degradation motifs) are involved in the cell cycle (A) and specifically in the mitotic spindle checkpoint (B).

Figure 3.

Surface representation showing two MAPK docking motifs bound to the MAPK docking groove. Negative charges and positive charges are shown in red and blue, respectively, on MAPK and the docking motif is rendered in yellow. (A) The N- to C-terminal orientation of the MAPK docking motif shown for the DOC_MAPK_NFAT4_5 motif (with regular expression: [RK][∧P][∧P][LIM].L.[LIVMF]). Here, charged amino acids [RK] are followed by hydrophobic residues (PDB:2XS0; (43)). (B) The reverse MAPK docking motif shown for the DOC_MAPK_RevD_3 motif (with regular expression: [LIVMPFA].[LIV].1,2[LIVMP].4,6[LIV]..[RK][RK]), where the N-terminus has hydrophobic amino acids followed by charged residues (PDB:2Y9Q; (43)). Figures produced using Chimera (46).