The ELM server

ELM is a computational biology resource for investigating candidate functional sites in eukarytic proteins. Functional sites which fit to the description "linear motif" are currently specified as patterns using Regular Expression rules. To improve the predictive power, context-based rules and logical filters are being developed and applied to reduce the amount of false positives.

The current version of the ELM server provides core functionality including filtering by cell compartment, phylogeny, globular domain clash (using the SMART/Pfam databases) and structure. In addition, both the known ELM instances and any positionally conserved matches in sequences similar to ELM instance sequences are identified and displayed (see ELM instance mapper). Although the ELM resource contains a large collection of functional site motifs, the current set of motifs is not exhaustive.

ELM Webservices:

References:

ELM:

• ELM - the database of eukaryotic linear motifs
  Dinkel H, Michael S, Weatheritt RJ, Davey NE, Roey K, Altenberg B, Toedt G, Uyar B, Seiler M, Budd A, Joedicke L, Dammert M, Schroeter C, Hammer M, Schmidt T, Jehl P, McGuigan C, Dymecka M, Chica C, Luck K, Via A, Chatr-aryamontri A, Haslam N, Grebnev G, Edwards RJ, Steinmetz MO, Meiselbach H, Diella F, and Gibson TJ (2012). Nucleic Acids Res 2011 Nov 21
• Attributes of short linear motifs.
  Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B, Altenberg B, Budd A, Diella F, Dinkel H, Gibson TJ. (2011). Mol Biosyst. 2011 Sep 12.
• ELM: the status of the 2010 eukaryotic linear motif resource
  Gould, C M, Diella, F, Via, A, Puntervoll, P, Gemünd, C, Chabanis-Davidson, S, Michael, S, Sayadi, A, Bryne, J C, Chica, C, Seiler, M, Davey, N E, Haslam, N, Weatheritt, R J, Budd, A, Hughes, T, Pas, J, Rychlewski, L, Travè, G, Aasland, R, Helmer-Citterich, M, Linding, R, Gibson, T J. (2009). Nucleic Acids Res 2009 Nov 17
• A structure filter for the Eukaryotic Linear Motif Resource.
  Via A., Gould CM., Gemünd C., Gibson T.J., Helmer-Citterich M. (2009) BMC Bioinformatics, 24;10:351.
• Understanding eukaryotic linear motifs and their role in cell signaling and regulation
  Diella, F., Haslam, N., Chica, N., Budd, A., Michael, S., Brown, N. P. , Trave, G., Gibson, T.J. (2009). Frontiers in Bioscience 13, 6580-6603
• A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences.
  Chica C., Labarga A., Gould CM., Lopez R., Gibson T.J. (2008). BMC Bioinformatics, 6;9:229.
• ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins.
  Puntervoll, P., Linding, R., Gemünd, C., Chabanis-Davidson, S., Mattingsdal, M., Cameron, S., Martin, D. M. A., Ausiello, G., Brannetti, B., Costantini, A., Ferrè, F., Maselli, V., Via, A., Cesareni, G., Diella, F., Superti-Furga, G., Wyrwicz, L., Ramu, C., McGuigan, C., Gudavalli, R., Letunic, I., Bork, P., Rychlewski, L., Küster, B., Helmer-Citterich, M., Hunter, W. N., Aasland, R., & Gibson, T.J. (2003). Nucleic Acids Res., 31: 3625-3630.

External tools used:

• IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content.
  Dosztányi Z, Csizmók V, Tompa P, Simon I.
  Bioinformatics. 2005 Aug 15;21(16):3433-4. Epub 2005 Jun 14. PMID: 15955779
  
• SMART 6: recent updates and new developments.
  Letunic I, Doerks T, Bork P.
  Nucleic Acids Res. 2009 Jan;37:D229-32. Epub 2008 Oct 31. PMID: 18978020
• The Pfam protein families database.
  Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A. Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22. Epub 2009 Nov 17. PMID: 19920124
• GlobPlot: Exploring protein sequences for globularity and disorder.
  Linding R, Russell RB, Neduva V, Gibson TJ.
  Nucleic Acids Res. 2003 Jul 1;31(13):3701-8. PMID: 12824398
• Phospho.ELM: a database of phosphorylation sites - update 2011.
  Dinkel H, Chica C, Via A, Gould CM, Jensen LJ, Gibson TJ, Diella F.
  Nucleic Acids Res. 2011 Jan;39(Database issue):D261-7. Epub 2010 Nov 9. PMID: 21062810

Further Reading:

• Cell regulation: determined to signal discrete cooperation
  Gibson, T.J. (2009). Trends Biochem Sci., 34(10): 471-82

The ELM Consortium

The ELM consortium involves five European academic institutions and one biotechnology company, and was funded by EU.

EMBL (Germany) Toby Gibson's group is in the Biocomputing Unit at the European Molecular Biology Laboratory (EMBL). Toby is the coordinator of the ELM Consortium. Holger Dinkel is responsible for software development, server maintenance and the visual representations. Previous members of the ELM project team: Francesca Diella - siteseeing Kate Gould - software development Caroline McGuigan - siteseeing Sophie Chabanis - siteseeing Christine Gemünd - software development Rune Linding - scientific design University of Rome - Tor Vergata (Italy) The Centre for Molecular Bioinformatics of the Department of Biology at the University of Rome Tor Vergata is involved in the development of computational tools for the study of protein interaction and structure-function relationships. ELMers in Rome: Manuela Helmer Citterich - Group leader Gabrielle Ausiello - siteseeing Anna Costantini - siteseeing, experimentalist Simona Panni - siteseeing Allegra Via - structural filters Andreas Zanzoni - siteseeing University of Bergen (Norway) The field of interest of the group of Rein Aasland at the Department of Molecular Biology, University of Bergen is the influence of chromatin on gene expression. The Bergen team is responsible for siteseeing and informatics on functional sites in nuclear proteins. Full time ELMer: Pål Puntervoll - siteseeing, software development, webmaster Morten Mattingsdal - siteseeing BioInfo.PL (Poland) The main expertise of the BioInfo.PL group, headed by Leszek Rychlewski, is the development of protein structure prediction methods. The group will be responsible for adding an experimental ab initio filter to the ELM pipeline. ELMers at BioInfo.PL: Leszek Rychlewski - ab initio filter Krzysztof Ginalski - ab initio filter Andrzej Kierzek - system development Jakub Pas - structural filters Lucjan Wyrwicz - siteseeing Marcin von Grotthuss - structural filters University of Dundee (Scotland) The School of Life Sciences at Dundee is a centre for research into biological phosphorylation. The ELM partner is Bill Hunter who applies X-ray crystallography to the study of enzymatic processes. Full time ELMer: Scott Cameron - siteseeing David Martin - consultant (part time) CellZome (Germany) CellZome is a functional genomics company. Giulio Superti-Furga is the ELM partner whose research interests are in tyrosine phosphoylation. ELMers at CellZome: Francesca Diella - siteseeing Bernhard Kuster - mass spectrometry

Is your Company interested in sponsoring ELM?

Our consortium has made ELM into the largest resource for functional sites in proteins. Yet there is much that we would like to do in the future to enhance the resource. In order to do so, we need new sources of funding and support. If possible, we would like to keep the ELM webserver and pipeline resources free for all users including in Industry but we do not know if we will be able to sustain this in future.

If your company finds ELM useful, you might wish to enter an industrial sponsorship with us, e.g. by funding one or more ELM developers. As well as helping to ensure that ELM is applied effectively by you in-house, ELM partners all have extensive bioinformatics knowledge and could, for example, offer more general consultancy and training to their sponsors. Furthermore, your company may influence the future path of development of the ELM resource towards functionalities that will be particularly useful for your company.

If you are interested, send direct enquiries to: Dr. Toby J. Gibson, EMBL, Heidelberg or to one of our academic partners in Bergen, Dundee, Rome or Poznan:

Bergen partner: Dr. Rein Aasland
Dundee partner: Dr. Bill Hunter
Rome partner: Dr. Manuela Helmer Citterich
Poznan partner: Dr. Leszek Rychlewski