Top image

Press Release 2013

Heidelberg, Hinxton, Hamburg, 14 May 2013

But what does it do?

Most complete database to date of human phosphatases and their substrates

 

pr14may13_m

Substrate search made easy.

Credit: EMBL/Köhn.

pr14may13b_m

Web-like view of interactions.

Credit: EMBL/Köhn.

Click images to enlarge and for more information.

 
In a nutshell:
  • All phosphatases in human cells, and their substrates – online and fully searchable
  • Makes it easy to identify a phosphatase’s substrates, and suggest new ones
  • Could help explain unexpected side-effects of drugs
 

Although we know the tool’s general purpose, it can sometimes be difficult to tell if a specific pair of precision tweezers belongs to a surgeon or a master jeweller. It is now easier to solve similar conundrums about a type of protein that allows cells to react to their environment, thanks to scientists at the European Molecular Biology Laboratory (EMBL). Published today in Science Signaling, their work offers a valuable resource for other researchers.

Whether in your eye being hit by light, in your blood fighting off disease, or elsewhere throughout your body, cells have to react to changes in their environment. But first, a cell must ‘know’ the environment has changed. One of the ways in which that information is transmitted within the cell is through tags called phosphate ions, which are added to or removed from specific molecules depending on the exact message that has to be conveyed. The tools the cell uses to remove phosphate ions are proteins called phosphatases. But it’s not always obvious what molecules – or substrates – a particular phosphatase acts upon.

“One of the biggest challenges in phosphatase research is finding substrates, and this is what our work supports,” says Maja Köhn from EMBL in Heidelberg, Germany, who led the study. “We’ve made it easier to create hypotheses about the relationships between phosphatases and their substrates.”

Xun Li, a post-doctoral student shared by Köhn’s lab and those of Matthias Wilmanns at EMBL in Hamburg, Germany and Janet Thornton at EMBL-European Bioinformatics Institute (EMBL-EBI) in Hinxton, UK, compiled the most complete picture to date of all the phosphatases in human cells, and their substrates. The scientists also grouped phosphatases into families, based on their three-dimensional structure, which can influence what molecules a phosphatase can act upon.

This information allows researchers to easily identify a phosphatase’s known substrates, and suggest new substrates based on how similar it is to other phosphatases. The web-like overview of interactions could even help explain unforeseen side-effects of drugs designed to interfere with phosphatases or with their phosphate-adding counterparts, kinases. To enable others to make such connections, Köhn and colleagues have created a free online database, DEPOD.

“When people have unexpected results, this could be a place to find explanations,” says Thornton, head of EMBL-EBI. “DEPOD combines a wealth of information that can be explored in a variety of ways, to make it useful not just to phosphatase researchers but to the wider community.”

 

Further information:

DEPOD: the human DEPhOsphorylation Database

The EMBL Interdisciplinary Postdoctoral Program (EIPOD) under which Xun Li carried out this work

Source Article

Li, X., Wilmanns, M., Thornton, J., & Köhn, M. Elucidating Human Phosphatase-Substrate Networks. Published online in Science Signaling on 14 May 2013. DOI: 10.1126/scisignal.2003203.

Article Abstract

Phosphatases are crucially involved in cellular processes by dephosphorylating cellular components. Here, we describe a structure-based classification scheme for all active human phosphatases that reveals previously unrecognized relationships between them. By collating protein and non-protein substrates and integrating colocalization and co-expression data, we generated a human phosphatase-substrate network. Analysis of the protein sequences surrounding sites of dephosphorylation suggested that common recognition mechanisms may apply to both kinases and a subset of phosphatases. Analysis of three-dimensional substrate recognition by protein phosphatases revealed preferred domains in the substrates. We identified phosphatases with highly specific substrates and those with less specificity by examining the relationship between phosphatases, kinases, and their shared substrates and showed how this analysis can be used to generate testable hypotheses about phosphatase biological function. DEPOD (human DEPhOsphorylation Database, 1.0, www.DEPOD.org) is an online resource with information about active human phosphatases, their substrates, and the pathways in which they function. The database includes links to kinases and chemical modulators of phosphatase activity and contains a sequence-similarity search function for identifying related proteins in other species.

Press Contact

Sonia Furtado Neves
EMBL Press Officer, Meyerhofstraße 1, 69117 Heidelberg, Germany

Tel: +49 6221 387-8263
E-mail: sonia.furtado@embl.de

Policy regarding use

Press and Picture Releases

EMBL press and picture releases including photographs, graphics, movies and videos are copyrighted by EMBL. They may be freely reprinted and distributed for non-commercial use via print, broadcast and electronic media, provided that proper attribution to authors, photographers and designers is made.