Short linear motif

[1][2] The first definition was given by Tim Hunt:[3] "The sequences of many proteins contain short, conserved motifs that are involved in recognition and targeting activities, often separate from other functional properties of the molecule in which they occur.

These motifs are linear, in the sense that three-dimensional organization is not required to bring distant segments of the molecule together to make the recognizable unit.

Ligand SLiMs are often central to the formation of dynamic multi-protein complexes, however, they more commonly mediate regulatory interactions that control the stability, localisation or modification state of a protein.

[14] Finally, Liddle's Syndrome has been implicated with autosomal dominant activating mutations in the WW interaction motif in the β-(SCNNB_HUMA) and γ-(SCNNG_HUMA) subunits of the Epithelial sodium channel ENaC.

[15] These mutations abrogate the binding to the ubiquitin ligase NEDD4, thereby inhibiting channel degradation and prolonging the half-life of ENaC, ultimately resulting in increased Na+ reabsorption, plasma volume extension and hypertension.

[16] Viruses often mimic human SLiMs to hijack and disrupt a host's cellular machinery,[17][18][11] thereby adding functionality to their compact genomes without necessitating new virally encoded proteins.

E. Coli injects a protein, EspF(U), that mimics an autoinhibitory element of N-WASP into the host cell to activate actin-nucleating factors WASP.

[21] Success stories include the MDM2 motif analog Nutlin-3 and integrin targeting RGD-mimetic Cilengitide: Nutlin-3 antagonises the interaction of MDM2's SWIB domain with p53 thus stabilising p53 and inducing senescence in cancer cells.

[22] Cilengitide inhibits integrin-dependent signaling, causing the disassembly of cytoskeleton, cellular detachment and the induction of apoptosis in endothelial and glioma cells.

Recommended further reading:[18][27] SLiMs are usually described by regular expressions in the motif literature with the important residues defined based on a combination of experimental, structural and evolutionary evidence.

However, high throughput screening such as phage display has seen a large increase in the available information for many motifs classes allowing them to be described with sequence logos.

Several more specific and specialised databases also exist, PepCyber[31] and ScanSite[32] focus on smaller subsets of motifs, phosphopeptide binding and important signaling domains respectively.

Recent work has created the tool MiMosa[36] to expedite the annotation process and encourage semantically robust motif descriptions.

MoRFPred[44] and MoRFchibi SYSTEM[45][46][47] are SVM based predictors which utilize multiple features including local sequence physicochemical properties, long stretches of disordered regions and conservation in their predictions.