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elm.md 4.76 KiB

Short Linear Motifs

This text was largely adapted from a tutorial written by Holger Dinkel for the EMBO Practical Course on computational analysis of protein-protein interactions

Eukaryotic Linear Motifs

Eukaryotic Linear Motifs (or ELMS) sometimes also known as short Linear Motifs (SLiMs) are short sequences typically found in disordered regions that have important roles in the function of a protein.

The ELM database

The ELM database is a project who's ultimate goal it is to all occurences of ELMs and their function in all known proteins(!).

It consists of manually annotated entries carefully curated by experts in a particular field, working in a certain protein, or a particular motif. These annotators are responsible for contributing ELM classes, which represent linear motifs with a known function, and experimentally verified instances of this motif.

  • types There are 6 types of motifs: LIG: ligand binding, MOD: modification, TRG: targeting, DOC: docking, DEG: degradation, CLV: cleavage.

  • class is a sequence of amino acids with a given function, based on binding partner, modifying enzyme, acting peptidase and targeted subcellular localisation. Each class is defined by a regular expression

  • instance an manually annotated occurrence of a class in a protein, verified by a literature citable experiment.

Browsing content

Exercise 1: Browsing content

There are two main ways in which the ELM database content can be browsed.

Click on "ELM DB" -> "ELM Classes", or follow the link to the ELM classes page: http://elm.eu.org/elms to browse the ELM classes that have been annotated.

Use the search (or side filters) to find the ELM motif: DOC_CYCLIN_1

  • Question 1: What does this motif do?
  • Question 2: How many instances are annotated in the database?
  • Question 3: Which Gene Ontology terms is this motif associated with?

This motif was identified in P53 in the sequence: KKLMF

  • Question 4: What is the starting and finishing position of this sequence in P53?
  • Question 5: Which experimental protocols were used to infer the existence of this instance?
  • Question 6: How certain are we about this annotation?
  • Question 7: What activates P53 in the pathway to induce apoptosis?

Exercise 2: The ELM Prediction tool

Navigate to the "ELM predictions" page.

Search protein SRC_HUMAN (accession P12931) for ELMs using the following parameters:

  • Cell Compartment: Not specified
  • Motif Probability Cutoff: 100
  • Context information: (leave blank)

Some questions:

  • Question 1: How many instances do you find?
  • Question 2: What can you say about the globularity of the protein? Does it have globular and/or disordered regions?

Redo the above search, this time using the following parameters:

  • Cell Compartment: cytosol
  • Motif Probability Cutoff: 0.01
  • Context information: Homo sapiens

Some questions:

  • Question 3: How many instances do you find now?
  • Question 4: How many of the instances are manually annotated?
  • Question 5: Do the structural predictors/filters (SMART, GlobPlot, IUPRED, Secondary Structure) agree in terms of which regions are structured/disordered?
  • Question 6: Compare the location of the annotated instances with structural information at hand (IUPRED, Secondary Structure).
  • Question 7: How many deteced instances were removed by the SMART/Structure filter?
  • Question 8: For the annotated instances, which of the ELM classes require a phosphorylation at a certain residue of the motif? (Hint: This information can be found in the description of the ELM class)
  • Question 9: Which residue in SRC_HUMAN corresponds to this and can you find evidence for a phosphorylation of this residue (using Phospho.ELM)?

Exercise 3: The ELM Prediction tool

Search ELM using the protein name MDM4_HUMAN and look for the ‘USP binding motif’ DOC_USP7_MATH_1

  • Question 1: How many such motif instances are found in this protein sequence?
  • Question 2: How many of these have been exprimentally validated (i.e., are manually annotated?), and what are the "FP" annotations?

Exercise 4: Switches

Use the ELM "global search box" (on the top right) to search for the class LIG_SH3_2. (Just start typing, and wait for the autocomplete to finish).

Click on "LIG_SH3_2" to visit the class page.

  • Question 1: How many switches are annotated for this class?
  • Question 2: What is the mechanism that results in the switching event in SYNJ2_RAT?